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Sample records for age tumor site

  1. Habits of sun exposure and risk of malignant melanoma: an analysis of incidence rates in Norway 1955-1977 by cohort, sex, age, and primary tumor site

    SciTech Connect

    Magnus, K.

    1981-11-15

    Incidence data on malignant melanoma of the skin in Norway from 1955-1977, comprising a total of 5108 new cases, were analyzed according to cohort, sex, age, and primary tumor site. A continuous increase in incidence of approximately 7% per year was observed for both sexes during the study period. For trunk and lower limb melanomas, the increase and cohort variations in incidence were much greater than for face and neck melanoma. A difference between these site groups was also observed in the shape of the cohort curves of age-specific rates. This indicated that the trend in carcinogenic exposure through life was different for the face--neck and the trunk--lower limb. For the generations born 1930-1949, the incidence of malignant melanoma per area unit of skin was greater for the trunk and lower limb than for the face--neck. It is suggested that not only the cumulated dose, but also the intensity of solar radiation may be significant in the cause of malignant melanoma.

  2. Accelerated aging in the tumor microenvironment

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony

    2011-01-01

    Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor micro-environment induces a form of “accelerated aging,” which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy (“self-eating”) in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy “fuel” and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a “mutagenic motor” and allows cancer cells to buffer—at a distance—exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of “accelerated host aging” in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively “cutting off the fuel supply” for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics. PMID:21654190

  3. Age-related trends in injection site reaction incidence induced by the tumor necrosis factor-α (TNF-α) inhibitors etanercept and adalimumab: the Food and Drug Administration adverse event reporting system, 2004-2015

    PubMed Central

    Matsui, Toshinobu; Umetsu, Ryogo; Kato, Yamato; Hane, Yuuki; Sasaoka, Sayaka; Motooka, Yumi; Hatahira, Haruna; Abe, Junko; Fukuda, Akiho; Naganuma, Misa; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2017-01-01

    Tumor necrosis factor-α (TNF-α) inhibitors are increasingly being used as treatment for rheumatoid arthritis (RA). However, the administration of these drugs carries the risk of inducing injection site reaction (ISR). ISR gives rise to patient stress, nervousness, and a decrease in quality of life (QoL). In order to alleviate pain and other symptoms, early countermeasures must be taken against this adverse event. In order to improve understanding of the risk factors contributing to the induction of ISR, we evaluated the association between TNF-α inhibitors and ISR by applying a logistic regression model to age-stratified data obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The FAERS database contains 7,561,254 reports from January 2004 to December 2015. Adjusted reporting odds ratios (RORs) (95% Confidence Intervals) were obtained for interaction terms for age-stratified groups treated with etanercept (ETN) and adalimumab (ADA). The adjusted RORs for ETN* ≥ 70 and ADA* ≥ 70 groups were the lowest among the age-stratified groups undergoing the respective monotherapies. Furthermore, we found that crude RORs for ETN + methotrexate (MTX) combination therapy and ADA + MTX combination therapy were lower than those for the respective monotherapies. This study was the first to evaluate the relationship between aging and ISR using the FAERS database. PMID:28260984

  4. 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

  5. Site-specific tumor-targeted fluorescent contrast agents

    NASA Astrophysics Data System (ADS)

    Achilefu, Samuel I.; Bugaj, Joseph E.; Dorshow, Richard B.; Jimenez, Hermo N.; Rajagopalan, Raghavan; Wilhelm, R. Randy; Webb, Elizabeth G.; Erion, Jack L.

    2001-01-01

    Site-specific delivery of drugs and contrast agents to tumors protects normal tissues from the cytotoxic effect of drugs, and enhances the contrast between normal and diseased tissues. In optical medicine, biocompatible dyes can be used as photo therapeutics or as contrast agents. Previous studies have shown that the use of covalent or non-covalent dye conjugates of carries such as antibodies, liposomes, and polysaccharides improves the delivery of such molecules to tumors. However, large biomolecules can elicit adverse immunogenic reactions and also result in prolonged blood circulation times, delaying visualization of target tissues. A viable alternative to this strategy is to use small bioactive molecule-dye conjugates. These molecules have several advantages over large biomolecules, including ease of synthesis of a variety of high purity compounds for combinatorial screening of new targets, enhanced diffusivity to solid tumors, and the ability to affect the pharmocokinetics of the conjugates by minor structural changes. Thus, we conjugated a near IR light absorbing dye to bioactive peptides that specifically target over expressed tumor receptors in established rat tumor lines. High tumor uptake of the conjugates was obtained without loss of either the peptide receptor affinity or the dye fluorescence. These findings demonstrate the efficacy of a small peptide-dye conjugate strategy for in vivo tumor imaging. Site-specific delivery of photodynamic therapy agents may also benefit form this approach.

  6. Placental site trophoblastic tumor, report of a case with unusual presentation.

    PubMed

    Behnamfar, F; Mousavi, A; Rezapourian, P; Zamani, A

    2013-05-01

    Placental site trophoblastic tumor (PSTT) is the rarest type of gestational trophoblastic tumors. Common presentation is irregular vaginal bleeding. A 26-year-old G1P1 woman presented with 15 month amenorrhea, a large uterine mass and plateau low level of serum human chorionic gonadotropin (hCG) which raised the possibility of PSTT. Since whole myometrium had been substituted with the large tumoral mass, hysterectomy was considered despite the young age of the patient. The patient has been in remission 36 months postoperatively without receiving any adjuvant treatment. It seems that plateau low levels of hCG in the presence of amenorrhea should prompt the possibility of PSTT.

  7. Age, Tumor Characteristics, and Treatment Regimen as Event Predictors in Ewing: A Children's Oncology Group Report

    PubMed Central

    Marina, Neyssa; Granowetter, Linda; Grier, Holcombe E.; Womer, Richard B.; Randall, R. Lor; Marcus, Karen J.; McIlvaine, Elizabeth; Krailo, Mark

    2015-01-01

    Purpose. To associate baseline patient characteristics and relapse across consecutive COG studies. Methods. We analyzed risk factors for LESFT patients in three randomized COG trials. We evaluated age at enrollment, primary site, gender, tumor size, and treatment (as randomized). We estimated event-free survival (EFS, Kaplan-Meier) and compared risk across groups (log-rank test). Characteristics were assessed by proportional hazards regression with the characteristic of interest as the only component. Confidence intervals (CI) for RR were derived. Factors related to outcome at level 0.05 were included in a multivariate regression model. Results. Between 12/1988 and 8/2005, 1444 patients were enrolled and data current to 2001, 2004, or 2008 were used. Patients were with a median age of 12 years (0–45), 55% male and 88% Caucasian. The 5-year EFS was 68.3% ± 1.3%. In univariate analysis age, treatment, and tumor location were identified for inclusion in the multivariate model, and all remained significant (p < 0.01). Since tumor size was not collected in the last study, the other two were reanalyzed. This model identified age, treatment, tumor location, and tumor size as significant predictors. Conclusion. Age > 18 years, pelvic tumor, size > 8 cms, and chemotherapy without ifosfamide/etoposide significantly predict worse outcome. AEWS0031 is NCT00006734, INT0091 and INT0054 designed before 1993 (unregistered). PMID:26508901

  8. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy.

    PubMed

    Bouchlaka, Myriam N; Sckisel, Gail D; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E; Maverakis, Emanual; Wilkins, Danice E C; Alderson, Kory L; Hsiao, Hui-Hua; Weiss, Jonathan M; Monjazeb, Arta M; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L; Blazar, Bruce R; Wiltrout, Robert H; Redelman, Doug; Taub, Dennis D; Murphy, William J

    2013-10-21

    Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice.

  9. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy

    PubMed Central

    Bouchlaka, Myriam N.; Sckisel, Gail D.; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E.; Maverakis, Emanual; Wilkins, Danice E.C.; Alderson, Kory L.; Hsiao, Hui-Hua; Weiss, Jonathan M.; Monjazeb, Arta M.; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L.; Blazar, Bruce R.; Wiltrout, Robert H.; Redelman, Doug; Taub, Dennis D.

    2013-01-01

    Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice. PMID:24081947

  10. Accelerated aging in the tumor microenvironment: connecting aging, inflammation and cancer metabolism with personalized medicine.

    PubMed

    Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony; Sotgia, Federica

    2011-07-01

    Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor microenvironment induces a form of "accelerated aging," which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy ("self-eating") in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy "fuel" and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a "mutagenic motor" and allows cancer cells to buffer-at a distance-exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of "accelerated host aging" in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively "cutting off the fuel supply" for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics.

  11. A Pentagram Suture Technique for Closing Tumor Resection Sites in the Face

    PubMed Central

    Takeuchi, Masaki; Mori, Satoko; Sakurai, Hiroyuki

    2015-01-01

    Background: Resection of facial skin tumors aims to remove the tumors completely and make the surgical scar unnoticeable as much as possible. By improving the purse string suture method, we developed a new pentagram suture technique that enables simple and safe suturing of small to large defects with early satisfactory esthetic outcomes. The surgical outcomes of a case series were examined in this report. Methods: As in drawing a unicursal star, 5 suture sites were marked at specific intervals around the defect area. A needle with 5-0 polydioxanone suture was passed from the subcutaneous tissue to the superficial dermal layer at one site and then from the superficial dermal layer to the subcutaneous layer at the next site, and the process was repeated until the pentagram was complete. When apposition was not tight enough, a couple of external stitches were added using 6-0 nylon suture. Results: In 13 patients (16 benign or malignant tumors; mean age, 51.1 years) with a mean tumor size of 10.1 ± 5.2 mm and postoperative skin defect diameter of 12.1 ± 8.2 mm, closure did not result in high tension on the suture, and there was reduced mechanical stress at the wound margin. Surgical outcomes were good esthetically at 6 months after surgery without keloid formation or scar contracture. None of the patients had postoperative pain, infection, or tumor recurrence. Conclusions: This simple alternative method for the closure of facial skin defects after skin tumor excision could be performed easily and provided satisfactory surgical outcomes. PMID:26495212

  12. Two faces of p53: aging and tumor suppression

    PubMed Central

    Rodier, Francis; Campisi, Judith; Bhaumik, Dipa

    2007-01-01

    The p53 tumor suppressor protein, often termed guardian of the genome, integrates diverse physiological signals in mammalian cells. In response to stress signals, perhaps the best studied of which is the response to DNA damage, p53 becomes functionally active and triggers either a transient cell cycle arrest, cell death (apoptosis) or permanent cell cycle arrest (cellular senescence). Both apoptosis and cellular senescence are potent tumor suppressor mechanisms that irreversibly prevent damaged cells from undergoing neoplastic transformation. However, both processes can also deplete renewable tissues of proliferation-competent progenitor or stem cells. Such depletion, in turn, can compromise the structure and function of tissues, which is a hallmark of aging. Moreover, whereas apoptotic cells are by definition eliminated from tissues, senescent cells can persist, acquire altered functions, and thus alter tissue microenvironments in ways that can promote both cancer and aging phenotypes. Recent evidence suggests that increased p53 activity can, at least under some circumstances, promote organismal aging. Here, we discuss the role of p53 as a key regulator of the DNA damage responses, and discuss how p53 integrates the outcome of the DNA damage response to optimally balance tumor suppression and longevity. PMID:17942417

  13. Site-specifically radioiodinated antibody for targeting tumors

    SciTech Connect

    Rea, D.W.; Ultee, M.E.; Belinka, B.A. Jr.; Coughlin, D.J.; Alvarez, V.L. )

    1990-02-01

    Labeling of an antibody site specifically through its carbohydrate regions preserves its antigen-binding activity. Previously site-specific labeling studies have conjugated antibodies with metallic radioisotopes or drugs. We now report site-specific labeling with a new radioiodinated compound, 2-hydroxy-5-iodo-3-methylbenzoyl hydrazide, whose synthesis we described earlier. The compound is reacted with aldehyde groups produced by specific oxidation of the carbohydrate portion of the antibody with sodium m-periodate. Optimized conjugation conditions give good recovery of active antibody containing 10 groups per molecule. The conjugate is stable in solution for at least several weeks at both 4 and -70 degrees C. When injected into nude mice bearing LS174T human cancer xenografts, the conjugate of B72.3 antibody localizes well to tumor tissue, with low uptake by other organs. This biodistribution is similar to that of conjugate prepared by using solid-phase chloramine-T (Iodohead). There are only two significant differences. First, the carbohydrate conjugate is much less susceptible to dehalogenation, and thus shows much less thyroid uptake. Secondly, the biological half-life of the carbohydrate conjugate was about half that of the chloramine-T one. This could be due primarily to lysis of the hydrazine bond through which the antibody is attached to the compound, which would then be excreted rapidly by itself. The new reagent will be especially useful for antibodies which either cannot be labeled by chloramine-T methods, or whose activity is impaired by them.

  14. Xeroderma pigmentosum skin: an immune privilege site for tumor development.

    PubMed

    Abid, Kalthoum; El Mezni, Faouzi; Kamoun, Mohamed Ridha; Fazaa, Becima; Zermani, Rachida; Hadouchi, Chokri; Hamzaoui, Kamel

    2010-04-01

    A unique feature of the skin immune system is its proximity to cells continuously exposed to sun rays, as it is located in the interface between the body and the environment. In this study, we aimed to determine the impact of DNA damaged keratinocytes on the expression of apoptotic-related molecules, in T-cells of the inflammatory component of the tumor environment. Immunohistochemistry was performed on tissue sections derived from skin biopsies of basal cell carcinomas (BCCs) of xeroderma pigmentosum (XP) patients, non-XP patients and nevoid basal cell carcinoma syndrome (NBCCS) patients, using antibodies against B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), CD95, CD3, CD8 and CD56. Our results showed significantly lower levels of expression of the antiapoptotic Bcl-2 molecule, in XP, in comparison with non-XP and NBCCS T-lymphocytes, leading to the highest Bax/Bcl-2 ratio for XP T-cells. For the CD95 receptor expression levels, there were significant differences among T-cells of the three patient subgroups as well. The higher propensity of XP T-cells to undergo apoptosis may have evolved in individual XP patients, apparently during the course of their disease, to maintain a special skin as an immune privilege site for tumors' development.

  15. Presentation of Placental Site Trophoblastic Tumor with Amenorrhea

    PubMed Central

    Behnamfar, Fariba; Rouholamin, Safoura; Esteki, Mahboubeh

    2017-01-01

    Placental site throphoblastic tumor (PSTT) is a rare manifestation of gestational trophoblastic neoplasia that may complicate any type of pregnancy. The disease is unique from other type, and is defined by slow growth, low human chorionic gonadotropin (hCG) serum levels, the late-onset metastatic potential, and most significantly, insensitivity to chemotherapy. We describe a case of a 31-year-old woman with prolonged amenorrhea and slightly elevated serum beta hCG (βhCG) level, referred for termination of abnormal pregnancy. During curettage, necrotic tissue was removed and severs vaginal bleeding was controlled with medical therapy. Histology examination showed neoplastic intermediate trophoblastic cells with invasion to the vessel wall compatible with PSTT. After that, hysterectomy was down and serum βhCG declined to undetectable level 2 weeks after surgery and was followed for 2 years without complication.

  16. 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

  17. Breed- and age-related differences in canine mammary tumors

    PubMed Central

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-01-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  18. Breed- and age-related differences in canine mammary tumors.

    PubMed

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted.

  19. 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.

  20. The role of fibronectin in tumor implantation at surgical sites.

    PubMed

    Murthy, M S; Scanlon, E F; Silverman, R H; Goodheart, C R; Goldschmidt, R A; Jelachich, M L

    1993-03-01

    Fibronectins are a family of glycoproteins with modular functional domains. They mediate cell-cell and cell-matrix interactions which are important in embryogenesis, wound healing, metastasis and other processes. We present data on the influence of fibronectin on wound implantation of a murine mammary carcinoma line, TA3Ha. Fibronectin used in these studies was derived from bovine plasma, human serum, human foreskin fibroblasts, and mouse embryo cultures. TA3Ha cells rarely form tumors in the liver of syngeneic mice when injected intravenously but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Wound implantation is markedly reduced when the cells are pre-exposed to 200 micrograms/ml bovine plasma fibronectin (13%, P = 0.007), human serum fibronectin (0%, P = 0.02), human cellular fibronectin (0%, P = 0.02), or mouse cellular fibronectin (0%, P = 0.04). Lung colonization is also reduced by these fibronectins. These effects are not due to a cytotoxic action of fibronectin, since intraperitoneally injected fibronectin-treated cells form ascites tumor as effectively as do control untreated cells. Local application of a solution containing 0.25 mg/ml mouse cellular fibronectin to the hepatic wound reduces the frequency of tumor implantation from 45% to 5% (1/21, P = 0.001). No tumor implantation inhibition is seen when only suspending medium or albumin in suspending medium is used. The mechanism by which topical application of fibronectin reduces hepatic wound implantation of tumor cells is unclear, but this finding raises an exciting possibility of preventing local recurrence of cancer.

  1. Caveolin-1 and Accelerated Host Aging in the Breast Tumor Microenvironment

    PubMed Central

    Mercier, Isabelle; Camacho, Jeanette; Titchen, Kanani; Gonzales, Donna M.; Quann, Kevin; Bryant, Kelly G.; Molchansky, Alexander; Milliman, Janet N.; Whitaker-Menezes, Diana; Sotgia, Federica; Jasmin, Jean-François; Schwarting, Roland; Pestell, Richard G.; Blagosklonny, Mikhail V.; Lisanti, Michael P.

    2013-01-01

    Increasing chronological age is the most significant risk factor for human cancer development. To examine the effects of host aging on mammary tumor growth, we used caveolin (Cav)-1 knockout mice as a bona fide model of accelerated host aging. Mammary tumor cells were orthotopically implanted into these distinct microenvironments (Cav-1+/+ versus Cav-1−/− age-matched young female mice). Mammary tumors grown in a Cav-1–deficient tumor microenvironment have an increased stromal content, with vimentin-positive myofibroblasts (a marker associated with oxidative stress) that are also positive for S6-kinase activation (a marker associated with aging). Mammary tumors grown in a Cav-1–deficient tumor microenvironment were more than fivefold larger than tumors grown in a wild-type microenvironment. Thus, a Cav-1–deficient tumor microenvironment provides a fertile soil for breast cancer tumor growth. Interestingly, the mammary tumor-promoting effects of a Cav-1–deficient microenvironment were estrogen and progesterone independent. In this context, chemoprevention was achieved by using the mammalian target of rapamycin (mTOR) inhibitor and anti-aging drug, rapamycin. Systemic rapamycin treatment of mammary tumors grown in a Cav-1–deficient microenvironment significantly inhibited their tumor growth, decreased their stromal content, and reduced the levels of both vimentin and phospho-S6 in Cav-1–deficient cancer-associated fibroblasts. Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues). PMID:22698676

  2. Potential Noachian-Aged Sites for MER-B

    NASA Astrophysics Data System (ADS)

    Gilmore, M. S.; Tanaka, K. L.

    2001-01-01

    Two Mars Exploration Rovers (MER) are slated for launch in 2003 and will land in the equatorial region of Mars. These rovers are More formidable in both size and instrument complement than the Sojourner rover, potentially allowing greater range. For landing, they will be housed in an airbag system nearly identical to Pathfinder allowing them to land in an area with elevation below 1.3 km, Root Mean Square (RMS) slopes less than 6 degrees, rock abundance less than 20%, and fine component thermal inertia greater than 3-4 cgs units. MER-A may land between 15 S to 5 N and MER-B between 10 S and 10 N. Numerous sites have been identified by the JPL team as meeting the above engineering requirements for the landing of the rovers. Here we focus on a subset of these that lie in Noachian-aged terrain, as defined by Viking-era geologic mapping. This subset is further reduced by the first author's support of the selection (if possible) of a site in the Valles Marineris which can only be reached by MER-A, this study therefore focuses on those Noachian-aged sites that can be reached by MER-B.

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

    PubMed

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

    2015-12-01

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

  4. Common Fragile Site Tumor Suppressor Genes and Corresponding Mouse Models of Cancer

    PubMed Central

    Drusco, Alessandra; Pekarsky, Yuri; Costinean, Stefan; Antenucci, Anna; Conti, Laura; Volinia, Stefano; Aqeilan, Rami I.; Huebner, Kay; Zanesi, Nicola

    2011-01-01

    Chromosomal common fragile sites (CFSs) are specific mammalian genomic regions that show an increased frequency of gaps and breaks when cells are exposed to replication stress in vitro. CFSs are also consistently involved in chromosomal abnormalities in vivo related to cancer. Interestingly, several CFSs contain one or more tumor suppressor genes whose structure and function are often affected by chromosomal fragility. The two most active fragile sites in the human genome are FRA3B and FRA16D where the tumor suppressor genes FHIT and WWOX are located, respectively. The best approach to study tumorigenic effects of altered tumor suppressors located at CFSs in vivo is to generate mouse models in which these genes are inactivated. This paper summarizes our present knowledge on mouse models of cancer generated by knocking out tumor suppressors of CFS. PMID:21318118

  5. Common fragile site tumor suppressor genes and corresponding mouse models of cancer.

    PubMed

    Drusco, Alessandra; Pekarsky, Yuri; Costinean, Stefan; Antenucci, Anna; Conti, Laura; Volinia, Stefano; Aqeilan, Rami I; Huebner, Kay; Zanesi, Nicola

    2011-01-01

    Chromosomal common fragile sites (CFSs) are specific mammalian genomic regions that show an increased frequency of gaps and breaks when cells are exposed to replication stress in vitro. CFSs are also consistently involved in chromosomal abnormalities in vivo related to cancer. Interestingly, several CFSs contain one or more tumor suppressor genes whose structure and function are often affected by chromosomal fragility. The two most active fragile sites in the human genome are FRA3B and FRA16D where the tumor suppressor genes FHIT and WWOX are located, respectively. The best approach to study tumorigenic effects of altered tumor suppressors located at CFSs in vivo is to generate mouse models in which these genes are inactivated. This paper summarizes our present knowledge on mouse models of cancer generated by knocking out tumor suppressors of CFS.

  6. Tumor-derived mesenchymal stem cells and orthotopic site increase the tumor initiation potential of putative mouse mammary cancer stem cells derived from MMTV-PyMT mice.

    PubMed

    Lanza, Denise Grant; Ma, Jun; Guest, Ian; Uk-Lim, Chang; Glinskii, Anna; Glinsky, Gennadi; Sell, Stewart

    2012-12-01

    The ability to transplant mammary cancer stem cells, identified by the phenotype CD24(+)CD29(+)CD49f(+)Sca-1(low), is dependent on the microenvironment in which the cells are placed. Using the MMTV-PyMT mouse model of mammary cancer, we now report two methods of tumor growth enhancement: contributions of tumor stroma in the form of tumor-derived mesenchymal stem cells and orthotopic vs. heterotopic transplantation sites. To support evidence of stem cell function, tumor-derived mesenchymal stem cells differentiated into adipocyte- and osteocyte-like cells after culture in specific medium. Co-injection of tumor-initiating cells with tumor-derived mesenchymal stem cells significantly increased tumor initiation compared to subcutaneous injection of TICs alone; co-injection also allowed tumor initiation with a single TIC. Interestingly, we observed the formation of sarcomas after co-injections of tumor-derived mesenchymal stem cells or mouse embryonic fibroblasts with TICs; sarcomas are not observed in spontaneous MMTV-PyMT tumors and rarely observed in injections of TICs alone. Tumor initiation was also significantly increased in the orthotopic injection site compared to heterotopic injections. We conclude that tumor stroma and orthotopic sites both enhance tumor initiation by mammary cancer stem cells.

  7. Effect of Gibberellic Acid on Crown Gall Tumor Induction in Aging Primary Pinto Bean Leaves 1

    PubMed Central

    Anand, Vinod K.; Bauer, Chris; Heberlein, Gary T.

    1975-01-01

    Gibberellic acid was tested for its effect on tumor induction by Agrobacterium tumefaciens in primary pinto bean (Phaseolus vulgaris) leaves in various stages of development. The hormone was found to promote tumor induction in partially aged leaves but did not effect tumor induction in very young leaves or in fully matured leaves. It is suggested that the natural loss of susceptibility to tumor induction in maturing pinto bean leaves is associated with a concomitant loss of endogenous gibberellins and/or a sensitivity to gibberellins. PMID:16659201

  8. Immunotherapy of Malignant Tumors in the Brain: How Different from Other Sites?

    PubMed Central

    Dutoit, Valérie; Migliorini, Denis; Dietrich, Pierre-Yves; Walker, Paul R.

    2016-01-01

    Immunotherapy is now advancing at remarkable pace for tumors located in various tissues, including the brain. Strategies launched decades ago, such as tumor antigen-specific therapeutic vaccines and adoptive transfer of tumor-infiltrating lymphocytes are being complemented by molecular engineering approaches allowing the development of tumor-specific TCR transgenic and chimeric antigen receptor T cells. In addition, the spectacular results obtained in the last years with immune checkpoint inhibitors are transfiguring immunotherapy, these agents being used both as single molecules, but also in combination with other immunotherapeutic modalities. Implementation of these various strategies is ongoing for more and more malignancies, including tumors located in the brain, raising the question of the immunological particularities of this site. This may necessitate cautious selection of tumor antigens, minimizing the immunosuppressive environment and promoting efficient T cell trafficking to the tumor. Once these aspects are taken into account, we might efficiently design immunotherapy for patients suffering from tumors located in the brain, with beneficial clinical outcome. PMID:28003994

  9. 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

  10. Comparing the landcapes of common retroviral insertion sites across tumor models

    NASA Astrophysics Data System (ADS)

    Weishaupt, Holger; Čančer, Matko; Engström, Cristopher; Silvestrov, Sergei; Swartling, Fredrik J.

    2017-01-01

    Retroviral tagging represents an important technique, which allows researchers to screen for candidate cancer genes. The technique is based on the integration of retroviral sequences into the genome of a host organism, which might then lead to the artificial inhibition or expression of proximal genetic elements. The identification of potential cancer genes in this framework involves the detection of genomic regions (common insertion sites; CIS) which contain a number of such viral integration sites that is greater than expected by chance. During the last two decades, a number of different methods have been discussed for the identification of such loci and the respective techniques have been applied to a variety of different retroviruses and/or tumor models. We have previously established a retrovirus driven brain tumor model and reported the CISs which were found based on a Monte Carlo statistics derived detection paradigm. In this study, we consider a recently proposed alternative graph theory based method for identifying CISs and compare the resulting CIS landscape in our brain tumor dataset to those obtained when using the Monte Carlo approach. Finally, we also employ the graph-based method to compare the CIS landscape in our brain tumor model with those of other published retroviral tumor models.

  11. The degree of intratumor mutational heterogeneity varies by primary tumor sub-site

    PubMed Central

    Eterovic, Agda Karina; Wick, Jo; Chen, Ken; Zhao, Hao; Tazi, Loubna; Manna, Pradip; Kerley, Spencer; Joshi, Radhika; Wang, Lin; Chiosea, Simion I.; Garnett, James David; Tsue, Terance Ted; Chien, Jeremy; Mills, Gordon B.; Grandis, Jennifer Rubin; Thomas, Sufi Mary

    2016-01-01

    In an era where mutational profiles inform treatment options, it is critical to know the extent to which tumor biopsies represent the molecular profile of the primary and metastatic tumor. Head and neck squamous cell carcinoma (HNSCC) arise primarily in the mucosal lining of oral cavity and oropharynx. Despite aggressive therapy the 5-year survival rate is at 50%. The primary objective of this study is to characterize the degree of intratumor mutational heterogeneity in HNSCC. We used multi-region sequencing of paired primary and metastatic tumor DNA of 24 spatially distinct samples from seven patients with HNSCC of larynx, floor of the mouth (FOM) or oral tongue. Full length, in-depth sequencing of 202 genes implicated in cancer was carried out. Larynx and FOM tumors had more than 69.2% unique SNVs between the paired primary and metastatic lesions. In contrast, the oral tongue HNSCC had only 33.3% unique SNVs across multiple sites. In addition, HNSCC of the oral tongue had fewer mutations than larynx and FOM tumors. These findings were validated on the Affymetrix whole genome 6.0 array platform and were consistent with data from The Cancer Genome Atlas (TCGA). This is the first report demonstrating differences in mutational heterogeneity varying by subsite in HNSCC. The heterogeneity within laryngeal tumor specimens may lead to an underestimation of the genetic abnormalities within tumors and may foster resistance to standard treatment protocols. These findings are relevant to investigators and clinicians developing personalized cancer treatments based on identification of specific mutations in tumor biopsies. PMID:27034009

  12. Placental site trophoblastic tumor: a case report and review of the literature

    PubMed Central

    Lucas, Rita; Cunha, Teresa Margarida; Santos, Filipa Batista

    2015-01-01

    We present a case of a gravida 1 para 1 woman, who presented with an 11-month history of amenorrhea after cesarean delivery. The patient was taking birth control pills at the time of presentation. She was observed with a slight elevation of serum β-hCG level, an enlarged heterogeneous uterus and hematometra. A biopsy was performed, and the patient was diagnosed with placental site trophoblastic tumor; the patient then underwent surgery. Placental site trophoblastic tumor is the rarest form of gestational trophoblastic disease, derived from intermediate trophoblast cells. It does not have a pathognomonic appearance; therefore, correlation with medical history, as well as results of laboratory tests and pathological analysis is mandatory. It is a relatively chemoresistant tumor, posing considerable therapeutic challenges; patients with localized disease are managed with surgery and those with metastatic disease require additional chemotherapy. Herein, we review the main features of this entity and top differential diagnosis, as the rarity of this tumor is associated with imaging and pathological pitfalls, reinforcing the need for further experience in this field. PMID:26622924

  13. Mucosal vaccines: novel strategies and applications for the control of pathogens and tumors at mucosal sites.

    PubMed

    Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis Cs; Badoual, Cecile; Tartour, Eric

    2014-01-01

    The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites.

  14. 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.

  15. Old age at diagnosis increases risk of tumor progression in nasopharyngeal cancer

    PubMed Central

    He, Yao-Xuan; Chen, Xiao-Di; Zhang, Guo-Ye; Li, Zhi-Kun; Hong, Jing; Xie, Dan; Cai, Mu-Yan

    2016-01-01

    Age at diagnosis has been found to be a prognostic factor of outcomes in various cancers. However, the effect of age at diagnosis on nasopharyngeal cancer (NPC) progression has not been explored. We retrospectively evaluated the relationship between age and disease progression in 3,153 NPC patients who underwent radiotherapy, chemotherapy, or chemoradiotherapy between 2007 and 2009. Patients were randomly assigned to either a testing cohort or a validation cohort by computer-generated random assignment. X-tile plots determined the optimal cut-point of age based on survival status to be ≤61 vs. >61 years. Further correlation analysis showed that age >61 years was significantly correlated with the tumor progression and therapeutic regimen in both testing and validation cohorts (P <0.05). In the present study, we observed that older age (>61 years) was a strong and independent predictor of poor disease-free survival (DFS) and cancer-specific survival (CSS), in both univariate and multivariate analyses. Age was also found to be a significant prognostic predictor as well (P <0.05) when evaluating patients with the same disease stage. ROC analysis confirmed the predictive value of age on NPC-specific survival in both cohorts (P <0.001) and suggested that age may improve the ability to discriminate outcomes in NPCs, especially regarding tumor progression. In conclusion, our study suggests that older age at NPC diagnosis is associated with a higher incidence of tumor progression and cancer-specific mortality. Age is a strong and independent predictor of poor outcomes and may allow for more tailored therapeutic decision-making and individualized patient counseling. PMID:27463012

  16. Caveolin-1 and accelerated host aging in the breast tumor microenvironment: chemoprevention with rapamycin, an mTOR inhibitor and anti-aging drug.

    PubMed

    Mercier, Isabelle; Camacho, Jeanette; Titchen, Kanani; Gonzales, Donna M; Quann, Kevin; Bryant, Kelly G; Molchansky, Alexander; Milliman, Janet N; Whitaker-Menezes, Diana; Sotgia, Federica; Jasmin, Jean-François; Schwarting, Roland; Pestell, Richard G; Blagosklonny, Mikhail V; Lisanti, Michael P

    2012-07-01

    Increasing chronological age is the most significant risk factor for human cancer development. To examine the effects of host aging on mammary tumor growth, we used caveolin (Cav)-1 knockout mice as a bona fide model of accelerated host aging. Mammary tumor cells were orthotopically implanted into these distinct microenvironments (Cav-1(+/+) versus Cav-1(-/-) age-matched young female mice). Mammary tumors grown in a Cav-1-deficient tumor microenvironment have an increased stromal content, with vimentin-positive myofibroblasts (a marker associated with oxidative stress) that are also positive for S6-kinase activation (a marker associated with aging). Mammary tumors grown in a Cav-1-deficient tumor microenvironment were more than fivefold larger than tumors grown in a wild-type microenvironment. Thus, a Cav-1-deficient tumor microenvironment provides a fertile soil for breast cancer tumor growth. Interestingly, the mammary tumor-promoting effects of a Cav-1-deficient microenvironment were estrogen and progesterone independent. In this context, chemoprevention was achieved by using the mammalian target of rapamycin (mTOR) inhibitor and anti-aging drug, rapamycin. Systemic rapamycin treatment of mammary tumors grown in a Cav-1-deficient microenvironment significantly inhibited their tumor growth, decreased their stromal content, and reduced the levels of both vimentin and phospho-S6 in Cav-1-deficient cancer-associated fibroblasts. Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues).

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

    PubMed

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

    2015-02-01

    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.

  18. 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

  19. Is Bax/Bcl-2 Ratio Considered as a Prognostic Marker with Age and Tumor Location in Colorectal Cancer?

    PubMed Central

    Khodapasand, Ehsan; Jafarzadeh, Narges; Farrokhi, Farid; Kamalidehghan, Behnam; Houshmand, Massoud

    2015-01-01

    Background: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate. Methods: In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer. Results: The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors. Conclusion: This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer. PMID:25864810

  20. 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.

  1. Placental-site trophoblastic tumor with PET scan-detected surgically treated lung metastasis.

    PubMed

    Nieves, Lucybeth; Hoffman, James; Allen, Gretchen; Currie, John; Sorosky, Joel I

    2008-06-01

    Metastatic placental-site trophoblastic tumor (PSTT) continues to be a diagnostic and management dilemma due to its relative resistance to chemotherapy and the difficulties in diagnosing such a rare tumor. We describe a 35-year-old woman with PSTT presenting with irregular bleeding and a mass in the lung. Dilation and curettage provided the diagnosis of PSTT by frozen section of the specimen. Subsequently, a total abdominal hysterectomy was performed and the patient received three cycles of EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine) Positron emission tomography (PET) scan confirmed a persistent lung nodule that was treated with wedge resection. She is currently in clinical remission. Surgery may have a role in salvaging a patient with persistent PET-positive disease after chemotherapy.

  2. 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.

  3. Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation

    SciTech Connect

    Migliori, R.J.; Gruber, S.A.; Sawyer, M.D.; Hoffman, R.; Ochoa, A.; Bach, F.H.; Simmons, R.L.

    1987-08-01

    Successful adoptive cancer immunotherapy presumably depends on the accumulation of tumoricidal leukocytes at the sites of tumor growth. Large numbers of lymphokine-activated killer (LAK) cells can be generated in vitro by growth in high concentrations of interleukin-2 (IL-2), but relatively few arrive at the tumor site after intravenous injection. We hypothesize that the delivery of LAK cells to tumor sites may be augmented by previously demonstrated lymphocyte-recruiting factors, including activated macrophage products such as interleukin-1 (IL-1) and tumor necrosis factor. /sup 111/Indium-labeled LAK cells were injected intravenously into syngeneic mice bearing the macrophage activator endotoxin (LPS) in one hind footpad, and saline solution was injected into the contralateral footpad. Significantly more activity was recovered from the LPS-bearing footpad at all times during a 96-hour period. Recombinant IL-1 also attracted more LAK cells after injection into tumor-free hind footpads. Furthermore, LAK cells preferentially homed to hind footpads that were bearing 3-day established sarcomas after intralesional injections of LPS, IL-1, or tumor necrosis factor when compared with contralateral tumor-bearing footpads injected with saline solution alone. In preliminary experiments, mice with hind-footpad tumors appeared to survive longer after combined systemic IL-2 and LAK therapy if intralesional LPS was administered. These studies demonstrate that macrophage activation factors that have been shown capable of attracting circulating normal lymphocytes can also effectively attract LAK cells from the circulation. By the stimulation of macrophages at the sites of tumor growth, more LAK cells can be attracted. It is hoped that by focusing the migration of LAK cells to tumors, LAK cells and IL-2 would effect tumor regression more efficiently and with less toxicity.

  4. 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…

  5. The Oral Cavity and Age: A Site of Chronic Inflammation?

    PubMed Central

    Bäck, Magnus; Hlawaty, Hanna; Labat, Carlos; Michel, Jean-Baptiste; Brink, Charles

    2007-01-01

    Background Aging may be accompanied by a low grade chronic up-regulation of inflammatory mediators. A variety of endogenous locally released mediators as well as inflammatory cells have been reported in the human oral cavity. The aim of this investigation was to determine the presence of different classes of inflammatory mediators in human saliva and correlate the levels with age. Methodology and Principal Findings Unstimulated whole buccal salivary samples were obtained in the morning from 94 healthy volunteers within 30 minutes after waking. None of the participants had taken aspirin in the week prior to the saliva collection. Lysozyme activity, eicosanoid levels (prostaglandin E2 and leukotriene B4) and MMP-9 activity were measured. The antimicrobial activity (lysozyme activity) was not correlated with age whereas PGE2 levels were markedly correlated with age (r = 0.29; P<0.05; n = 56). Saliva from healthy subjects (≤40 years) compared with data derived from older volunteers (>40 years) demonstrated a significant increase in the mean values for PGE2 and MMP-9 activity with age. In addition, significant correlations were observed between LTB4 and PGE2 (r = 0.28; P<0.05; n = 56) and between LTB4 levels and MMP-9 activity in smokers (r = 0.78; P<0.001; n = 15). Conclusions/Significance The presence of significant levels and activity of inflammatory mediators in saliva suggests that the oral cavity of healthy subjects may be in a constant low state of inflammation associated with age. PMID:18159234

  6. Multiple specific binding sites for purified glucocorticoid receptors on mammary tumor virus DNA.

    PubMed

    Payvar, F; Firestone, G L; Ross, S R; Chandler, V L; Wrange, O; Carlstedt-Duke, J; Gustafsson, J A; Yamamoto, K R

    1982-01-01

    Glucocorticoid hormones selectively stimulate the rate of transcription of integrated mammary tumor virus (MTV) sequences in infected rat hepatoma cells. Using two independent assays, we find that purified rat liver glucocorticoid receptor protein binds specifically to at least four widely separated regions on pure MTV proviral DNA. One of these specific binding domains, which itself contains at least two distinct receptor binding sites, resides within a fragment of viral DNA that maps 110-449 bp upstream of the promoter for MTV RNA synthesis. Three other binding domains lie downstream of the promoter and within the MTV primary transcription unit. Restriction fragments bearing separate binding domains have been introduced into cultured cells; transformants have been recovered in which the introduced fragments are expressed under glucocorticoid control. Thus, it appears that this assay will be useful for assessing the biological significance of the receptor binding sites detected in vitro.

  7. Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4.

    PubMed

    Fernandez, Patricia; Scaffidi, Paola; Markert, Elke; Lee, Ji-Hyeon; Rane, Sushil; Misteli, Tom

    2014-10-09

    Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS) provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis.

  8. 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.

  9. Drosophila OVO regulates ovarian tumor transcription by binding unusually near the transcription start site.

    PubMed

    Lü, J; Oliver, B

    2001-05-01

    Evolutionarily conserved ovo loci encode developmentally regulated, sequence-specific, DNA-binding, C(2)H(2)-zinc-finger proteins required in the germline and epidermal cells of flies and mice. The direct targets of OVO activity are not known. Genetic experiments suggest that ovo acts in the same regulatory network as ovarian tumor (otu), but the relative position of these genes in the pathway is controversial. Three OVO-binding sites exist in a compact regulatory region that controls germline expression of the otu gene. Interestingly, the strongest OVO-binding site is very near the otu transcription start, where basal transcriptional complexes must function. Loss-of-function, gain-of-function and promoter swapping constructs demonstrate that OVO binding near the transcription start site is required for OVO-dependent otu transcription in vivo. These data unambiguously identify otu as a direct OVO target gene and raise the tantalizing possibility that an OVO site, at the location normally occupied by basal components, functions as part of a specialized core promoter.

  10. The profile of tumor antigens which can be targeted by immunotherapy depends upon the tumor's anatomical site.

    PubMed

    Alonso-Camino, Vanesa; Rajani, Karishma; Kottke, Timothy; Rommelfanger-Konkol, Diana; Zaidi, Shane; Thompson, Jill; Pulido, Jose; Ilett, Elizabeth; Donnelly, Oliver; Selby, Peter; Pandha, Hardev; Melcher, Alan; Harrington, Kevin; Diaz, Rosa Maria; Vile, Richard

    2014-11-01

    Previously, we showed that vesicular stomatitis virus (VSV) engineered to express a cDNA library from human melanoma cells (ASMEL, Altered Self Melanoma Epitope Library) was an effective systemic therapy to treat subcutaneous (s.c.) murine B16 melanomas. Here, we show that intravenous treatment with the same ASMEL VSV-cDNA library was an effective treatment for established intra-cranial (i.c.) melanoma brain tumors. The optimal combination of antigens identified from the ASMEL which treated s.c. B16 tumors (VSV-N-RAS+VSV-CYTC-C+VSV-TYRP-1) was ineffective against i.c. B16 brain tumors. In contrast, combination of VSV-expressed antigens-VSV-HIF-2α+VSV-SOX-10+VSV-C-MYC+VSV-TYRP1-from ASMEL which was highly effective against i.c. B16 brain tumors, had no efficacy against the same tumors growing subcutaneously. Correspondingly, i.c. B16 tumors expressed a HIF-2α(Hi), SOX-10(Hi), c-myc(Hi), TYRP1, N-RAS(lo)Cytc(lo) antigen profile, which differed significantly from the HIF-2α(lo), SOX-10(lo), c-myc(lo), TYRP1, N-RAS(Hi)Cytc(Hi) phenotype of s.c. B16 tumors, and was imposed upon the tumor cells by CD11b(+) cells within the local brain tumor microenvironment. Combining T-cell costimulation with systemic VSV-cDNA treatment, long-term cures of mice with established i.c. tumors were achieved in about 75% of mice. Our data show that the anatomical location of a tumor profoundly affects the profile of antigens that it expresses.

  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. [Testosterone production by tumor tissue in partial androgen deficiency in aged men (PADAM)].

    PubMed

    Pecherskiĭ, A V; Semiglazov, V F; Komiakov, B K; Guliev, B G; Gorelov, A I; Novikov, A I; Pecherskiĭ, V I; Simonov, N N; Guliaev, A V; Samusenko, I A

    2005-01-01

    The aim of the study was examination of cause-effect relationships between PADAM, extragonadal production of androgens and high proliferative activity in aged men. The study group included 15 patients aged between 53 and 79 years with prostatic cancer (n = 5), urinary bladder cancer (n = 5) and cancer of the rectum (n = 5). Control samples of tissues of the prostatic gland, urinary bladder and rectum were obtained from dead bodies of men at the age between 18 and 29 years killed in the accidents at the age from 18 to 29 years. Testosterone levels in the tissues of peritumor zone of the prostate, in tumor tissue of patients with cancer of the prostate, urinary bladder and the rectum were higher than in blood serum. In prostatic cancer, testosterone in the tumor tissue was higher than in the tissues of prostatic peritumor zone. The values of Histochemical score AR of the peritumor zone in prostatic cancer patients were higher than those of the control group. It was detected that ER, PR, bcl-2, Ki-67 and p53 in prostatic tissue of young controls were absent while in patients with prostatic cancer these factors were expressed in the peritumor zone. In cancer of the urinary bladder, peritumor zone showed expression of PR, bcl-2, Ki-67 and p53, while no such expression was in the controls. ER, bcl-2, Ki-67 and p53 were registered in the peritumor zone of patients with cancer of the rectum but the controls had neither ER, bcl-2 nor p53 while Ki-67 expression in rectal cancer was higher than in the controls. The results of the study suggest that testosterone production by some tumors and tissues of the peritumor zone accompanied with high proliferative activity and dysregulation of the cell cycle is secondary to PADAM. These changes arise to compensate testicular deficiency and are manifestations of metabolic syndrome (X-syndrome). In this situation immune system fails to utilize all atypical cells.

  13. 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.

  14. Age and sex differences in estimated tibia strength: influence of measurement site.

    PubMed

    Sherk, Vanessa D; Bemben, Debra A

    2013-01-01

    Variability in peripheral quantitative computed tomography (pQCT) measurement sites and outcome variables limit direct comparisons of results between studies. Furthermore, it is unclear what estimates of bone strength are most indicative of changes due to aging, disease, or interventions. The purpose of this study was to examine age and sex differences in estimates of tibia strength. An additional purpose of this study was to determine which tibia site or sites are most sensitive for detecting age and sex differences in tibia strength. Self-identifying Caucasian men (n=55) and women (n=59) aged 20-59yr had their tibias measured with pQCT from 5% to 85% of limb length in 10% increments distal to proximal. Bone strength index, strength strain index (SSI), moments of inertia (Ip, Imax, and Imin), and strength-to-mass ratios (polar moment of inertia to total bone mineral content [BMC] ratio [Ip:Tot.BMC] and strength strain index to total BMC ratio [SSI:Tot.BMC]) were quantified. There were significant (p<0.01) site effects for all strength variables and strength-to-mass ratios. Site×sex interaction effects were significant (p<0.05) for all strength variables. Men had greater (p<0.01) values than women for all strength variables. Sex differences in Ip, Imax, Ip:Tot.BMC, SSI, and SSI:Tot.BMC ratios were the smallest at the 15% site and peaked at various sites, depending on variable. Site×age interactions existed for Imax, Ip:Tot.BMC, and SSI:Tot.BMC. There were significant age effects, Imax, Ip:Tot.BMC, and SSI:Tot.BMC, as values were the lowest in the 20-29 age group. Age and sex differences varied by measurement site and variable, and larger sex differences existed for moments of inertia than SSI. Strength-to-mass ratios may reflect efficiency of the whole bone architecture.

  15. 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.

  16. 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

  17. 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

    2016-05-03

    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.

  18. Grapefruit-Derived Nanovectors Use an Activated Leukocyte Trafficking Pathway to Deliver Therapeutic Agents to Inflammatory Tumor Sites.

    PubMed

    Wang, Qilong; Ren, Yi; Mu, Jingyao; Egilmez, Nejat K; Zhuang, Xiaoyin; Deng, Zhongbin; Zhang, Lifeng; Yan, Jun; Miller, Donald; Zhang, Huang-Ge

    2015-06-15

    Inflammation is a hallmark of cancer. Activated immune cells are intrinsically capable of homing to inflammatory sites. Using three inflammatory-driven disease mouse models, we show that grapefruit-derived nanovectors (GNV) coated with inflammatory-related receptor enriched membranes of activated leukocytes (IGNVs) are enhanced for homing to inflammatory tumor tissues. Blocking LFA-1 or CXCR1 and CXCR2 on the IGNVs significantly inhibits IGNV homing to the inflammatory tissue. The therapeutic potential of IGNVs was further demonstrated by enhancing the chemotherapeutic effect as shown by inhibition of tumor growth in two tumor models and inhibiting the inflammatory effects of dextran sulfate sodium-induced mouse colitis. The fact that IGNVs are capable of homing to inflammatory tissue and that chemokines are overexpressed in diseased human tissue provides the rationale for using IGNVs to more directly deliver therapeutic agents to inflammatory tumor sites and the rationale for the use of IGNVs as treatment for certain cancers in personalized medicine.

  19. Grapefruit-derived nanovectors use an activated leukocyte trafficking pathway to deliver therapeutic agents to inflammatory tumor sites

    PubMed Central

    Wang, Qilong; Ren, Yi; Mu, Jingyao; Egilmez, Nejat; Zhuang, Xiaoyin; Deng, Zhongbin; Zhang, Lifeng; Yan, Jun; Miller, Donald; Zhang, Huang-Ge

    2015-01-01

    Inflammation is a hallmark of cancer. Activated immune cells are intrinsically capable of homing to inflammatory sites. Using three inflammatory driven disease mouse models, we show that grapefruit-derived nanovectors (GNVs) coated with inflammatory related receptor enriched membranes of activated leukocytes (IGNVs) are enhanced for homing to inflammatory tumor tissues. Blocking LFA-1 or CXCR1 and CXCR2 on the IGNVs significantly inhibits IGNV homing to the inflammatory tissue. The therapeutic potential of IGNVs was further demonstrated by enhancing the chemotherapeutic effect as shown by inhibition of tumor growth in two tumor models and inhibiting the inflammatory effects of DSS induced mouse colitis. The fact that IGNVs are capable of homing to inflammatory tissue and that there is an overexpression of chemokines in diseased human tissue provides the rationale for using IGNVs to more directed delivery of therapeutic agents to inflammatory tumor sites and the use of IGNVs as personalized medicine for treatment of certain cancers. PMID:25883092

  20. Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response.

    PubMed

    Hazan, Idit; Hofmann, Thomas G; Aqeilan, Rami I

    2016-12-01

    The role of common fragile sites (CFSs) in cancer remains controversial. Two main views dominate the discussion: one suggests that CFS loci are hotspots of genomic instability leading to inactivation of genes encoded within them, while the other view proposes that CFSs are functional units and that loss of the encoded genes confers selective pressure, leading to cancer development. The latter view is supported by emerging evidence showing that expression of a given CFS is associated with genome integrity and that inactivation of CFS-resident tumor suppressor genes leads to dysregulation of the DNA damage response (DDR) and increased genomic instability. These two viewpoints of CFS function are not mutually exclusive but rather coexist; when breaks at CFSs are not repaired accurately, this can lead to deletions by which cells acquire growth advantage because of loss of tumor suppressor activities. Here, we review recent advances linking some CFS gene products with the DDR, genomic instability, and carcinogenesis and discuss how their inactivation might represent a selective advantage for cancer cells.

  1. Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response

    PubMed Central

    Hazan, Idit; Hofmann, Thomas G.; Aqeilan, Rami I.

    2016-01-01

    The role of common fragile sites (CFSs) in cancer remains controversial. Two main views dominate the discussion: one suggests that CFS loci are hotspots of genomic instability leading to inactivation of genes encoded within them, while the other view proposes that CFSs are functional units and that loss of the encoded genes confers selective pressure, leading to cancer development. The latter view is supported by emerging evidence showing that expression of a given CFS is associated with genome integrity and that inactivation of CFS-resident tumor suppressor genes leads to dysregulation of the DNA damage response (DDR) and increased genomic instability. These two viewpoints of CFS function are not mutually exclusive but rather coexist; when breaks at CFSs are not repaired accurately, this can lead to deletions by which cells acquire growth advantage because of loss of tumor suppressor activities. Here, we review recent advances linking some CFS gene products with the DDR, genomic instability, and carcinogenesis and discuss how their inactivation might represent a selective advantage for cancer cells. PMID:27977694

  2. Imaging and Clinical Data of Placental Site Trophoblastic Tumor: A Case Report

    PubMed Central

    Niknejadi, Maryam; Ahmadi, Firoozeh; Akhbari, Farnaz

    2016-01-01

    Placental site trophoblastic tumor (PSTT) is a very rare variant of gestational trophoblastic tumor. It can occur after normal termination of pregnancy or spontaneous abortion and ectopic or molar pregnancy. There is a wide range of clinical manifestations from a benign condition to an aggressive disease with fatal outcome. One of the most important characteristics of PSTT, unlike other forms of gestational trophoblastic diseases (GTD) is the presence of low beta-subunit of human chorionic gonadotropin (β-hCG) levels because it is a neoplastic proliferation of intermediate trophoblastic cells. However, human placental lactogen (hPL) is increased on histologic section and in the serum of patients too. We present a case of PSTT and discuss the differential diagnosis in order to further familiarize physicians with the diagnosis and treatment of this disease. It has a varied clinical spectrum and usually presents with irregular vaginal bleeding or amenorrhea. Diagnosis is confirmed by dilatation and curettage (D and C) and hysterectomy. Because chemotherapy is not effective, surgery is the cornerstone of treatment. This case is presented because it is a rare neoplasm with different treatments and it should be differentiated from molar pregnancy. PMID:27679689

  3. Leukocyte-mediated Delivery of Nanotherapeutics in Inflammatory and Tumor Sites

    PubMed Central

    Dong, Xinyue; Chu, Dafeng; Wang, Zhenjia

    2017-01-01

    Nanotechnology has become a powerful tool to potentially translate nanomedicine from bench to bedside. Nanotherapeutics are nanoparticles (NPs) loaded with drugs and possess the property of tissue targeting after surfaces of NPs are bio-functionalized. Designing smaller size of nanotherapeutics is presumed to increase tumor targeting based on the EPR (enhanced permeability and retention) effect. Since the immune systems possess a defence mechanism to fight diseases, there is an emerging concept that NPs selectively target immune cells to mediate the active delivery of drugs into sites of disease. In this review, we will focus on a key question of how nanotherapeutics specifically target immune cells and hijack them as a delivery vehicle to transport nanotherapeutics into disease tissues, thus possibly improving current therapies in inflammation, immune disorders and cancers. We will also discuss the challenges and opportunities for this new strategy of leukocyte-mediated delivery of nanotherapeutics. PMID:28255364

  4. 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.

  5. [Utilization of Werner syndrome mouse model in studying premature aging and tumor].

    PubMed

    Jia, Shu-Ting; Yang, Shi-Hua; Luo, Ying

    2009-08-01

    Werner syndrome (WS) is a rare autosomal recessive genetic disease in human. It is considered as a good model disease in studying human premature syndrome. Werner protein (WRN) is a nuclear protein mutated in WS. Recent biochemical and genetic studies indicated that WRN plays important roles in DNA replication, DNA repair, and telomere maintenance. Here, we reviewed the molecular genetics of WS and the importance of telomere and WRN in the development of WS. Knocking out both telomerase and Wrn genes in mouse faithfully manifests human WS. The mouse model provides a unique genetic platform to explore the crosstalk of premature aging and tumor.

  6. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some throat ...

  7. 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

  8. 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.

  9. Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor development in aging mice

    PubMed Central

    Grieb, Brian C.; Boyd, Kelli; Mitra, Ramkrishna; Eischen, Christine M.

    2016-01-01

    Alterations of specific genes can modulate aging. Myc, a transcription factor that regulates the expression of many genes involved in critical cellular functions was shown to have a role in controlling longevity. Decreased expression of Myc inhibited many of the deleterious effects of aging and increased lifespan in mice. Without altering Myc expression, reduced levels of Mtbp, a recently identified regulator of Myc, limit Myc transcriptional activity and proliferation, while increased levels promote Myc-mediated effects. To determine the contribution of Mtbp to the effects of Myc on aging, we studied a large cohort of Mtbp heterozygous mice and littermate matched wild-type controls. Mtbp haploinsufficiency significantly increased longevity and maximal survival in mice. Reduced levels of Mtbp did not alter locomotor activity, litter size, or body size, but Mtbp heterozygous mice did exhibit elevated markers of metabolism, particularly in the liver. Mtbp+/− mice also had a significant delay in spontaneous cancer development, which was most prominent in the hematopoietic system, and an altered tumor spectrum compared to Mtbp+/+ mice. Therefore, the data suggest Mtbp is a regulator of longevity in mice that mimics some, but not all, of the properties of Myc in aging. PMID:27803394

  10. Aging-associated B7-DC+ B cells enhance anti-tumor immunity via Th1 and Th17 induction.

    PubMed

    Tomihara, Kei; Shin, Takako; Hurez, Vincent J; Yagita, Hideo; Pardoll, Drew M; Zhang, Bin; Curiel, Tyler J; Shin, Tahiro

    2012-02-01

    Because most patients with cancer are aged and because immunological functions are altered during aging, it is important to account for aging-associated immunological alterations in the design of new cancer immunotherapies. We thus compared immune populations in young and aged mice and found that B7-DC(+) (PD-L2/CD273) B cells, a minor population in young mice, were significantly increased in aged mice. Induction of both Th1 and Th17 cells was significantly augmented by B7-DC(+) B cells from aged mice, and this effect was blocked with anti-B7-DC antibodies in vitro and in vivo. Moreover, retardation of tumor growth in aged mice was largely B7-DC dependent. Tumor growth in young mice was significantly inhibited by immunization with B7-DC(+) B cells from aged mice owing to increased induction of tumor antigen-specific cytotoxic T lymphocytes. These data indicate that B7-DC(+) B cells could play an important role in aging-associated cancer immunopathology as well as in other aging-associated diseases and further suggest that B7-DC(+) B cells have potential for future cancer immunotherapy.

  11. Derivation of site-specific skeletal masses within the current ICRP age series.

    PubMed

    Watchman, Christopher J; Hasenauer, Deanna; Bolch, Wesley E

    2007-06-07

    The calculation of absorbed dose to the radiosensitive tissues of the skeleton is routinely performed using reference masses provided in publications from the International Commission on Radiological Protection (ICRP). These values typically include total skeleton tissue masses by reference subject age, but not by individual bone site at a given age. Site-specific variations in absorbed fractions are known to occur for internal alpha-particle and beta-particle emitters, and in certain medical dose reconstructions, site-specific estimates of marrow dose may be desirable. Furthermore, bone-site-specific tissue masses are required to properly estimate skeletal-averaged absorbed fractions and, more importantly, specific absorbed fractions for internalized radionuclides and radiopharmaceuticals. Reference masses by skeletal site are also needed in the development of ICRP compliant tomographic phantoms, as this organ system is initially segmented from medical images only as a homogeneous tissue region. ICRP reference skeletal masses are assigned based upon several independent data sources, many of which may not be entirely consistent with one another. In this study, a methodology is presented, using data from the various ICRP publications, to derive site-specific skeletal tissue masses for each member of the ICRP age series. Active marrow masses are calculated and differences are shown with respect to ICRP Publications 70 and 89 values. New data for a revised surrogate tissue region for the osteoprogenitor cells within bone marrow is presented with estimates of its total mass throughout the skeleton and for different subject ages.

  12. 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

  13. Analysis of Surgical Site Infection after Musculoskeletal Tumor Surgery: Risk Assessment Using a New Scoring System

    PubMed Central

    Nagano, Satoshi; Yokouchi, Masahiro; Setoguchi, Takao; Sasaki, Hiromi; Shimada, Hirofumi; Kawamura, Ichiro; Ishidou, Yasuhiro; Kamizono, Junichi; Yamamoto, Takuya; Kawamura, Hideki; Komiya, Setsuro

    2014-01-01

    Surgical site infection (SSI) has not been extensively studied in musculoskeletal tumors (MST) owing to the rarity of the disease. We analyzed incidence and risk factors of SSI in MST. SSI incidence was evaluated in consecutive 457 MST cases (benign, 310 cases and malignant, 147 cases) treated at our institution. A detailed analysis of the clinical background of the patients, pre- and postoperative hematological data, and other factors that might be associated with SSI incidence was performed for malignant MST cases. SSI occurred in 0.32% and 12.2% of benign and malignant MST cases, respectively. The duration of the surgery (P = 0.0002) and intraoperative blood loss (P = 0.0005) was significantly more in the SSI group than in the non-SSI group. We established the musculoskeletal oncological surgery invasiveness (MOSI) index by combining 4 risk factors (blood loss, operation duration, preoperative chemotherapy, and the use of artificial materials). The MOSI index (0–4 points) score significantly correlated with the risk of SSI, as demonstrated by an SSI incidence of 38.5% in the group with a high score (3-4 points). The MOSI index score and laboratory data at 1 week after surgery could facilitate risk evaluation and prompt diagnosis of SSI. PMID:24672281

  14. Analysis of DNA methylation of potential age-related methylation sites in canine peripheral blood leukocytes.

    PubMed

    Ito, Genta; Yoshimura, Kuniko; Momoi, Yasuyuki

    2017-04-08

    Reliable methodology for predicting the age of mature dogs is currently unavailable. In this study, amplicon sequencing of 50 blood samples obtained from diseased dogs was used to measure methylation in seven DNA regions. Significant correlations between methylation level and age were identified in four of the seven regions. These four regions were then tested in samples from 31 healthy toy poodles, and correlations were detected in two regions. The age of another 11 dogs was predicted using data from the diseased dogs and the healthy poodles. The mean difference between the actual and calculated ages was 34.3 and 23.1 months, respectively. Further research is needed to identify additional sites of age-related methylation and allow accurate age prediction in dogs.

  15. 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.

  16. Influence of age and sex on winter site fidelity of sanderlings Calidris alba

    PubMed Central

    Alves, José A.; Reneerkens, Jeroen; Loonstra, AH Jelle; Potts, Peter M.; Granadeiro, José P.; Catry, Teresa

    2016-01-01

    Many migratory bird species show high levels of site fidelity to their wintering sites, which confers advantages due to prior knowledge, but may also limit the ability of the individual to move away from degrading sites or to detect alternative foraging opportunities. Winter site fidelity often varies among age groups, but sexual differences have seldom been recorded in birds. We studied a population of individually colour-marked sanderlings wintering in and around the Tejo estuary, a large estuarine wetland on the western coast of Portugal. For 160 individuals, sighted a total of 1,249 times between November 2009 and March 2013, we calculated the probability that they moved among five distinct wintering sites and how this probability is affected by distance between them. To compare site fidelity among age classes and sexes, as well as within the same winter and over multiple winters, we used a Site Fidelity Index (SFI). Birds were sexed using a discriminant function based on biometrics of a large set of molecularly sexed sanderlings (n = 990). The vast majority of birds were observed at one site only, and the probability of the few detected movements between sites was negatively correlated with the distance among each pair of sites. Hardly any movements were recorded over more than 15 km, suggesting small home ranges. SFI values indicated that juveniles were less site-faithful than adults which may reflect the accumulated knowledge and/or dominance of older animals. Among adults, females were significantly less site faithful than males. A sexual difference in winter site fidelity is unusual in shorebirds. SFI values show site-faithfulness is lower when multiple winters were considered, and most birds seem to chose a wintering site early in the season and use that site throughout the winter. Sanderlings show a very limited tendency to explore alternative wintering options, which might have implications for their survival when facing habitat change or loss (e

  17. 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.

  18. Dense and Non-dense Mammographic Area and Risk of Breast Cancer by Age and Tumor Characteristics

    PubMed Central

    Bertrand, Kimberly A.; Scott, Christopher G.; Tamimi, Rulla M.; Jensen, Matthew R.; Pankratz, V. Shane; Norman, Aaron D.; Visscher, Daniel W.; Couch, Fergus J.; Shepherd, John; Chen, Yunn-Yi; Fan, Bo; Wu, Fang-Fang; Ma, Lin; Beck, Andrew H.; Cummings, Steven R.; Kerlikowske, Karla; Vachon, Celine M.

    2015-01-01

    Background Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent MD with larger and node-positive tumors across all ages, and estrogen receptor (ER)-negative status among women ages <55 years. To provide insight into these associations, we examined the components of percent MD (dense area (DA) and non-dense area (NDA) with breast cancer subtypes. Methods Data were pooled from six studies including 4095 breast cancers and 8558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathological characteristics and receptor status were calculated using polytomous logistic regression. Results DA was associated with increased breast cancer risk [odds ratios (OR) for quartiles: 0.65, 1.00(Ref), 1.22, 1.55; p-trend <0.001] and NDA was associated with decreased risk [ORs for quartiles: 1.39, 1.00(Ref), 0.88, 0.72; p-trend <0.001] across all ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (p-trend<0.001) but no differences by nodal status. Among women <55 years, DA was more strongly associated with increased risk of ER+ vs. ER− tumors [p-heterogeneity (het) = 0.02] while NDA was more strongly associated with decreased risk of ER− vs. ER+ tumors [p-het = 0.03]. Conclusions DA and NDA have differential associations with ER+ vs. ER− tumors that vary by age. Impact DA and NDA are important to consider when developing age- and subtype-specific risk models. PMID:25716949

  19. Growth-inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro

    SciTech Connect

    Shimada, Y.; Kaji, K.; Ito, H.; Noda, K.; Matsuo, M. )

    1990-01-01

    We have examined the effects of in vitro aging on the growth capacity of human umbilical vein endothelial cells (HUVECs) under the influence of tumor necrosis factor (TNF) with or without interferon-gamma (IFN-gamma). The growth and colony-forming abilities of control cells were impaired with advancing age in vitro, especially at later stages (more than 70-80% of life span completed). It was found that treatment with TNF inhibited growth and colony-forming efficiency at any in vitro age. The effects of TNF were shown to increase with increasing in vitro age, as reflected by a more pronounced increase in doubling times, a decrease in saturation density, and a reduction in colony-forming efficiency. However, the characteristics of TNF receptors, including the dissociation constant, and the number of TNF-binding sites per cell-surface area remained rather constant. The effect of TNF was augmented by IFN-gamma at a dose that alone affected growth and colony formation only slightly. The augmentation by IFN-gamma was also found to depend on in vitro age; the synergy with TNF in the deterioration of colony-forming ability was observed only in aged cells. These results suggest that the intrinsic responsiveness of HUVECs to growth-inhibiting factors, as well as to growth-stimulating factors, changes during aging in vitro.

  20. Alfacalcidol increases cancellous bone in low turnover, fatty marrow sites in aged, orchidectomized rats.

    PubMed

    Tian, X Y; Chen, H Y; Setterberg, R B; Li, M; Jee, W S S

    2009-01-01

    The objectives of this study were to determine the responses of cancellous bone in the distal tibial metaphysis (DTM), a low turnover, fatty (yellow) marrow site, to sham-aged, orchidectomy (ORX) and alfacalcidol treatment in sham-aged and ORX rats. Eighteen-month-old male sham and ORX rats were treated with 0.1 and 0.2 microg/kg alfacalcidol 5 days/wk p.o. for 12 weeks, double fluorescent labeled, and the DTM were processed for bone histomorphometry analyses. The current study found the DTM in sham-aged male rats were resistant to age-related and ORX-induced cancellous bone loss and alfacalcidol-induced bone gain, findings that differ from that in the proximal tibial metaphysis (PTM) and lumbar vertebral body (LVB), two high turnover, red marrow bone sites. However, alfacalcidol treatment increased DTM bone mass in ORX rats where bone turnover was elevated by androgen deficiency. These results in concert with the previously positive findings in red marrow bone sites following alfacalcidol treatment suggest that alfacalcidol is more effective in increasing cancellous bone mass in the skeletal sites with higher bone turnover.

  1. Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site

    PubMed Central

    Kiefer, Jonathan D.; Neri, Dario

    2016-01-01

    Summary The activation of the immune system for a selective removal of tumor cells represents an attractive strategy for the treatment of metastatic malignancies, which cannot be cured by existing methodologies. In this review, we examine the design and therapeutic potential of immunocytokines and bispecific antibodies, two classes of bifunctional products which can selectively activate the immune system at the tumor site. Certain protein engineering aspects, such as the choice of the antibody format, are common to both classes of therapeutic agents and can have a profound impact on tumor homing performance in vivo of individual products. However, immunocytokines and bispecific antibodies display different mechanisms of action. Future research activities will reveal whether an additive of even synergistic benefit can be obtained from the judicious combination of these two types of biopharmaceutical agents. PMID:26864112

  2. 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.

  3. 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.

  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. Distribution of anionic sites on the capillary endothelium in an experimental brain tumor model.

    PubMed

    Vincent, S; DePace, D; Finkelstein, S

    1988-02-01

    The distribution of anionic domains on the capillary endothelium of experimental brain tumors was determined using cationic ferritin (CF) in order to ascertain whether the pattern of these domains is different from that on normal cerebral capillaries. Tumors were induced by stereotaxic injection of cultured neoplastic glial cells, A15A5, into the caudate nucleus of Sprague-Dawley rats. Following a 14-21 day growth period tumors appeared as vascularized, sharply circumscribed masses which caused compression of the surrounding brain tissue. Anionic domains were distributed in a patchy and irregular pattern on the luminal plasma membrane of the endothelia of blood vessels in the tumors. Some variability in this pattern was observed infrequently in limited regions of the tumor where there was either a continuous layer of CF or an absence of CF binding. Plasmalemmal vesicles, coated vesicles, coated pits, multivesicular bodies, and some junctional complexes showed varying degrees of labeling with the probe. Capillaries in the tumor periphery and normal cerebral vessels showed a uniform distribution of anionic groups. These results indicate that there is an altered surface charge on the endothelial luminal plasma membrane of blood vessels in brain tumors. A correlation may exist between the altered surface charge and the degree to which the blood-brain barrier is impaired in these vessels.

  6. 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.

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

    PubMed

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

    2015-11-10

    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.

  8. Analysis of Molecular Markers by Anatomic Tumor Site in Stage III Colon Carcinomas from Adjuvant Chemotherapy Trial NCCTG N0147 (Alliance)

    PubMed Central

    Sinicrope, Frank A.; Mahoney, Michelle R.; Yoon, Harry H.; Smyrk, Thomas C.; Thibodeau, Stephen N.; Goldberg, Richard M.; Nelson, Garth D.; Sargent, Daniel J.; Alberts, Steven R.

    2015-01-01

    PURPOSE To determine the frequency and prognostic association of molecular markers by anatomic tumor site in patients with stage III colon carcinomas. Experimental Design In a randomized trial of adjuvant FOLFOX + cetuximab, BRAFV600E and KRAS (exon 2) mutations and DNA mismatch repair (MMR) proteins were analyzed in tumors (N=3,018) in relationship to tumor location including subsite. Cox models were used to assess clinical outcome including overall survival (OS). RESULTS KRAS codon 12 mutations were most frequent at the splenic flexure and cecum; codon 13 mutations were evenly distributed. BRAF mutation frequency sharply increased from transverse colon to cecum in parallel with deficient (d) MMR. Non-mutated BRAF or KRAS tumors progressively decreased from sigmoid to transverse (all p<0.0001). Significantly poorer OS was found for mutant KRAS in distal [HR, 1.98 (1.49–2.63); p<.0001] vs proximal [1.25 (0.97–1.60), p=.079] cancers. BRAF status and outcome were not significantly associated with tumor site. Proximal vs distal dMMR tumors had significantly better outcome. An interaction test was significant for tumor site by KRAS (padjusted=.043) and MMR (padjusted=.010) for OS. Significant prognostic differences for biomarkers by tumor site were maintained in the FOLFOX arm. Tumor site was independently prognostic with a stepwise improvement from cecum to sigmoid (OS: padjusted=0.001). CONCLUSIONS Mutations in BRAF or KRAS codon 12 were enriched in proximal cancers whereas non-mutated BRAF/KRAS were increased in distal tumors. Significant differences in outcome for KRAS mutations and dMMR were found by tumor site, indicating that their interpretation should occur in the context of tumor location. PMID:26187617

  9. 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.

  10. Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age

    PubMed Central

    Crocker, Melissa K.; Gourgari, Evgenia; Stratakis, Constantine A.

    2014-01-01

    Context: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. Objective: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. Design: Case series of a very rare tumor and chart review of cases treated at other institutions. Setting: Tertiary care and referral center. Patients: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. Interventions: Patients were treated for a total of 6–60 months on AIT. Main Outcome Measures: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. Results: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. Conclusions: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy. PMID:25226294

  11. Tumor Necrosis Factor Gene Polymorphisms in Advanced Non-exudative Age-related Macular Degeneration

    PubMed Central

    Bonyadi, Mohammad Hossein Jabbarpoor; Bonyadi, Morteza; Ahmadieh, Hamid; Fotuhi, Nikoo; Shoeibi, Nasser; Saadat, Saeed; Yagubi, Zakieh

    2015-01-01

    Purpose: To investigate tumor necrosis factor (TNF)-α gene polymorphisms in advanced dry-type age-related macular degeneration (AMD) in a population from Northeastern Iran. Methods: In this case-control study, 50 patients with geographic macular atrophy and 73 gender-matched controls were enrolled. Genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood. Polymerase chain reaction was performed to analyze 2 candidate single nucleotide polymorphisms in the TNF-α gene, namely −1031 thymine (T)/cytosine (C) and −308 guanine (G)/adenine (A). Results: The distribution of the - 1031 T/C genotype was TT, 62%; TC, 36%; CC, 2% in the patients and TT, 60%; TC, 36%; CC, 4% in the controls (P = 0.94). Genotype analysis of TNF-α −308 also revealed no significant difference in distribution between patients (G, 78%; GA, 22%; AA, 0%) and controls (GG, 74%; GA, 23%; AA, 3%) (P = 0.51). None of the haplotypes nor alleles of studied TNF-α polymorphisms were significantly associated with advanced dry-type AMD. Conclusion: The findings of this study show that polymorphisms in the TNF-α gene, do not play an important role in dry-type AMD in the studied population. PMID:26425318

  12. 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.

  13. Mutations in the p53 and Ki-ras genes, microsatellite instability and site of tumor origin in colorectal cancer.

    PubMed

    Catalano, Teresa; Curia, Maria Cristina; Aceto, Gitana; Verginelli, Fabio; Cascinu, Stefano; Cama, Alessandro; Mariani-Costantini, Renato; Teti, Diana; Battista, Pasquale

    2005-09-01

    Using PCR-SSCP screening and direct sequencing we analyzed a series of 28 colorectal carcinomas for mutations in p53 (exons 5-8) and Ki-ras (codons 12, 13 and 61), and for micro-satellite instability (MSI) at BAT25 and BAT26, supplementing data with the analysis of the IARC colorectal cancer p53 mutation database. Mutations were correlated with the site of tumor origin (proximal or distal to the splenic flexure). We identified 19 mutations in p53, 9 in Ki-ras, and 4 MSI-positive cases in a total of 20 tumors. Only 6/20 cases (30%) carried mutations in both p53 and Ki-ras. Mutations in p53 were detected at similar frequencies in proximal and distal tumors, while IARC data pointed to a strong association of p53 mutations with distal cancers. Ki-ras mutations were more frequent in proximal tumors, and MSI occurred at similar frequencies in proximal and distal tumors and was associated with mutations in p53 or Ki-ras. The p53 mutations detected in the series analyzed, as well as those retrieved from the IARC database, were predominantly transitions, with no preferential sequence localization or nucleotide position. Ki-ras mutations were predominantly transversions in position 2 at codon 12. MSI-H occurred at similar frequencies in proximal and distal tumors and was associated with either p53 or Ki-ras mutations. Overall these data suggest that distinct mutagenic factors target p53 and Ki-ras in colorectal epithelium irrespective of MSI-H status.

  14. Salivary gland tumor "wishes" to add to the next WHO Tumor Classification: sclerosing polycystic adenosis, mammary analogue secretory carcinoma, cribriform adenocarcinoma of the tongue and other sites, and mucinous variant of myoepithelioma.

    PubMed

    Gnepp, Douglas R

    2014-03-01

    This review is a continuation of suggested tumor additions to the next WHO Tumor Classification. The author will focus on four salivary gland entities that have recently become accepted in the literature as new neoplastic entities: sclerosing polycystic adenosis, mammary analogue secretory carcinoma, cribriform adenocarcinoma of the tongue and other sites, and mucinous variant of myoepithelioma.

  15. Multi-Site Fatigue Testing and Characterization of Fuselage Panels from Aging Aircraft Structure

    DTIC Science & Technology

    2013-06-07

    Multi-site fatigue damage is a common problem in the riveted lap joint structure of aging aircraft. Modeling and characterization of such damage is...an especially daunting task. In this effort we present the results from fatigue tests which were performed on fuselage lap joints extracted from...in the lap joint . Some spot welded lap joint panels were also tested during the larger program; however, only the results from mechanically fastened

  16. 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

  17. Inhibition of tumor implantation at sites of trauma by Arg-Gly-Asp containing proteins and peptides.

    PubMed

    Murthy, M S; Weiss, B D; Miller, R J; Trueheart, R; Scanlon, E F

    1992-01-01

    We report on the inhibition of wound implantation by TA3Ha mammary carcinoma cells by Arg-Gly-Asp containing proteins and peptides using a hepatic wedge resection model. Intravenously injected TA3Ha cells rarely form tumor in the liver of syngeneic mice, but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Hepatic wound implantation is significantly (P = 0.01) inhibited by pretreating the cells with whole mouse plasma, but not with fibrinogen-depleted plasma or serum. Tumor inhibition is also achieved by pretreatment of cells with fibrinogen (P = 0.05-0.0004), fibronectin (P = 0.007) and laminin, but not by albumin. The active domain appears to be the RGDS sequence since the deca- and tetrapeptides containing RGDS inhibit wound implantation (P less than 0.05). However, the tetrapeptide Arg-Gly-Glu-Ser has no such activity. None of these agents affects ascites tumor formation by the intraperitoneally injected cells, suggesting that anchorage independent growth of cells is not affected. We propose that proteins and peptides containing RGD occupy the binding sites and prevent the cells from interacting with cell adhesion proteins in healing wounds. Proteins and/or peptides containing RGD may be useful for preventing local recurrence in postsurgical cancer patients.

  18. 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.

  19. 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.

  20. An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites.

    PubMed

    Fu, Xinping; Rivera, Armando; Tao, Lihua; Zhang, Xiaoliu

    2015-01-20

    Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home to tumor sites. We explored the possibility of using an oncolytic virus derived from HSV-2, which can actively pull T effector cells to the site of infection, as a local attractant for migration of adoptively transferred T cells. Our data show that intratumoral administration of this virus can indeed attract active migration of the adoptively transferred T cells to the treated tumor. Moreover, once attracted to the tumor site by the virus, T cells persisted in there significantly longer than in mock-treated tumor. Chemokine profiling identified significant elevation of CXCL9 and CXCL10, as well as several other chemokines belonging to the inflammatory chemokine family in the virus-treated tumors. These chemokines initially guided the T-cell migration to and then maintained their persistence in the tumor site, leading to a significantly enhanced therapeutic effect. Our data suggests that this virotherapy may be combined with adoptive T-cell therapy to potentiate its therapeutic effect against solid tumors that are otherwise difficult to manage with the treatment alone.

  1. Wnt3a expression is associated with MMP-9 expression in primary tumor and metastatic site in recurrent or stage IV colorectal cancer

    PubMed Central

    2014-01-01

    Background The wnt/β-catenin signaling pathway is known to affect in cancer oncogenesis and progression by interacting with the tumor microenvironment. However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been thoroughly studied. In the present study, we investigated the expression of wnt protein and the concordance rate in primary tumor and metastatic sites in CRC. To determine the relationship of wnt proteins with invasion related protein, we also analyzed the association between wnt protein expression and the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2). Methods Tumor tissue was obtained from eighty-three paraffin- embedded blocks which were using resected tissue from both the primary tumor and metastatic sites for each patient. We performed immunohistochemical staining for wnt3a, wnt5a, β-catenin, MMP-9 and VEGFR-2. Results Wnt3a, wnt5a, β-catenin, and MMP-9 expression was high; the proteins were found in over 50% of the primary tumors, but the prevalence was lower in tissue from metastatic sites. The concordance rates between the primary tumor and metastatic site were 76.2% for wnt5a and 79.4% for wnt3a and β-catenin, but VEGFR-2 was expressed in 67.4% of the metastatic sites even when not found in the primary tumor. Wnt3a expression in primary tumors was significantly associated with lymph node involvement (p = 0.038) and MMP-9 expression in the primary tumor (p = 0.0387), mesenchyme adjacent to tumor (p = 0.022) and metastatic site (p = 0.004). There was no other relationship in the expression of these proteins. Vascular invasion in primary tumor tissue may be a potential prognostic marker for liver metastasis, but no significant association was observed among the wnt protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, β-catenin expression was significantly correlated with overall survival (p = 0.05). Conclusions Wnt3a and wnt5a

  2. Estimation of methane emission rate changes using age-defined waste in a landfill site.

    PubMed

    Ishii, Kazuei; Furuichi, Toru

    2013-09-01

    Long term methane emissions from landfill sites are often predicted by first-order decay (FOD) models, in which the default coefficients of the methane generation potential and the methane generation rate given by the Intergovernmental Panel on Climate Change (IPCC) are usually used. However, previous studies have demonstrated the large uncertainty in these coefficients because they are derived from a calibration procedure under ideal steady-state conditions, not actual landfill site conditions. In this study, the coefficients in the FOD model were estimated by a new approach to predict more precise long term methane generation by considering region-specific conditions. In the new approach, age-defined waste samples, which had been under the actual landfill site conditions, were collected in Hokkaido, Japan (in cold region), and the time series data on the age-defined waste sample's methane generation potential was used to estimate the coefficients in the FOD model. The degradation coefficients were 0.0501/y and 0.0621/y for paper and food waste, and the methane generation potentials were 214.4 mL/g-wet waste and 126.7 mL/g-wet waste for paper and food waste, respectively. These coefficients were compared with the default coefficients given by the IPCC. Although the degradation coefficient for food waste was smaller than the default value, the other coefficients were within the range of the default coefficients. With these new coefficients to calculate methane generation, the long term methane emissions from the landfill site was estimated at 1.35×10(4)m(3)-CH(4), which corresponds to approximately 2.53% of the total carbon dioxide emissions in the city (5.34×10(5)t-CO(2)/y).

  3. A new age to an old site: the earliest Tupiguarani settlement in Rio de Janeiro State?

    PubMed

    Scheel-Ybert, Rita; Macario, Kita; Buarque, Angela; Anjos, Roberto M; Beauclair, Mariana

    2008-12-01

    This paper presents unexpectedly early dates for a Tupiguarani settlement in Southeastern Brazil. One radiocarbon dating of 1740 +/- 90 yr BP (1820-1390 cal yr BP) was already available for the Morro Grande site (Araruama, southeastern coast of Rio de Janeiro State). Two new dates, obtained from charcoal samples, are reported here. An age of 2920 +/- 70 yr BP (3220-2790 cal yr BP) was obtained from a specialized hearth, probably used for cooking ceramics; a funerary hearth at the same archaeological locus was dated at 2600 +/- 160 yr BP (3000-2150 cal yr BP). Both measurements were made independently, indifferent laboratories, arguing for their validity. These results considerably age the arrival time of Tupiguarani populations to the coastal region of Southeastern Brazil. They may have important implications to the hypotheses about the origin and dispersion of these populations from Amazonia, supporting the claim of recent authors who consider that their expansion must have begun well before 2000 yrs BP.

  4. Mammary tumors

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported.

  5. 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.

  6. Consensus topography in the ATP binding site of the simian virus 40 and polyomavirus large tumor antigens

    SciTech Connect

    Bradley, M.K.; Smith, T.F.; Lathrop, R.H.; Livingston, D.M.; Webster, T.A.

    1987-06-01

    The location and sequence composition of a consensus element of the nucleotide binding site in both simian virus 40 (SV40) and polyomavirus (PyV) large tumor antigens (T antigens) can be predicted with the assistance of a computer-based pattern-matching system, ARIADNE. The latter was used to optimally align elements of T antigen primary sequence and predicted secondary structure with a descriptor for a mononucleotide binding fold. Additional consensus elements of the nucleotide binding site in these two proteins were derived from comparisons of T antigen primary and predicted secondary structures with x-ray structures of the nucleotide binding sites in four otherwise unrelated proteins. Each of these elements was predicted to be encompassed within a 110-residue segment that is highly conserved between the two T antigens residues 418-528 in SV 40 T antigen and residues 565-675 in PyV. Results of biochemical and immunologic experiments on the nucleotide binding behavior of these proteins using (/sup 32/P)-Amp-labeled SV40 T antigen, were found to be consistent with these predictions. Taken together, the latter have resulted in a topological model of the ATP binding site in these two oncogene products.

  7. 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

  8. MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans.

    PubMed

    Riesen, Michèle; Feyst, Inna; Rattanavirotkul, Nattaphong; Ezcurra, Marina; Tullet, Jennifer M A; Papatheodorou, Irene; Ziehm, Matthias; Au, Catherine; Gilliat, Ann F; Hellberg, Josephine; Thornton, Janet M; Gems, David

    2014-02-01

    In C. elegans, increased lifespan in daf-2 insulin/IGF-1 receptor mutants is accompanied by up-regulation of the MDL-1 Mad basic helix-loop-helix leucine zipper transcription factor. Here we describe the role of mdl-1 in C. elegans germline proliferation and aging. The deletion allele mdl-1(tm311) shortened lifespan, and did so significantly more so in long-lived daf-2 mutants implying that mdl-1(+) contributes to effects of daf-2 on lifespan. mdl-1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl-1(tm311). Opposite phenotypes were seen in daf-2 mutants, i.e. mdl-1 and daf-2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL-1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age-related pathology in C. elegans (uterine tumors). In addition, intestine-limited rescue of mdl-1 increased lifespan but not to wild type levels. Thus, mdl-1 likely acts both in the intestine and the germline to influence age-related mortality.

  9. MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans

    PubMed Central

    Riesen, Michèle; Feyst, Inna; Rattanavirotkul, Nattaphong; Ezcurra, Marina; Tullet, Jennifer M.A.; Papatheodorou, Irene; Ziehm, Matthias; Au, Catherine; Gilliat, Ann F.; Hellberg, Josephine; Thornton, Janet M.; Gems, David

    2014-01-01

    In C. elegans, increased lifespan in daf-2 insulin/IGF-1 receptor mutants is accompanied by up-regulation of the MDL-1 Mad basic helix-loop-helix leucine zipper transcription factor. Here we describe the role of mdl-1 in C. elegans germline proliferation and aging. The deletion allele mdl-1(tm311) shortened lifespan, and did so significantly more so in long-lived daf-2 mutants implying that mdl-1(+) contributes to effects of daf-2 on lifespan. mdl-1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl-1(tm311). Opposite phenotypes were seen in daf-2 mutants, i.e. mdl-1 and daf-2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL-1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age-related pathology in C. elegans (uterine tumors). In addition, intestine-limited rescue of mdl-1 increased lifespan but not to wild type levels. Thus, mdl-1 likely acts both in the intestine and the germline to influence age-related mortality. PMID:24531613

  10. 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.

  11. 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.

  12. Common Integration Sites for MMTV in Viral Induced Mouse Mammary Tumors

    PubMed Central

    Callahan, Robert

    2011-01-01

    The paradigm of mammary cancer induction by the mouse mammary tumor virus (MMTV) is used to illustrate the body of evidence that supports the hypothesis that mammary epithelial stem/progenitor cells represent targets for oncogenic transformation. It is argued that this is not a special case applicable only to MMTV-induced mammary cancer, because MMTV acts as an environmental mutagen producing random interruptions in the somatic DNA of infected cells by insertion of proviral DNA copies. In addition to disrupting the host genome, the proviral DNA also influences gene expression through its associated enhancer sequences over significant inter-genomic distances. Genes commonly affected by MMTV insertion in multiple individual tumors include, the Wnt, FGF, RSpo gene families as well as eIF3e and Notch4. All of these gene families are known to play essential roles in stem cell maintenance and behavior in a variety of organs. The MMTV-induced mutations accumulate in cells that are long-lived and possess the properties of stem cells, namely, self-renewal and the capacity to produce divergent epithelial progeny through asymmetric division. The evidence shows that epithelial cells with these properties are present in normal mammary glands, may be infected with MMTV, become transformed to produce epithelial hyperplasia through MMTV-induced mutagenesis and progress to frank mammary malignancy. Retroviral marking via MMTV proviral insertion demonstrates that this process progresses from a single mammary epithelial cell that possesses all of the features ascribed to tissue-specific stem cells. PMID:18709449

  13. Melanotic neuroectodermal tumor of infancy: Cytology and histopathology of a rare lesion at an uncommon site.

    PubMed

    Batta, Nishant; Narang, Vikram; Kaur, Harpreet; Selhi, Pavneet Kaur; Sood, Neena

    2016-11-07

    Melanotic neuroectodermal tumour of infancy is a rare, pigmented neoplasm generally arising in infants during the first year of life. The cytological features are rarely described in the literature. This case due to its rarity and unusual site emphasising the cytopathological features and the necessity of histology for differentiating it from other round cell tumours has been presented. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

  14. Up-regulating telomerase and tumor suppressors: focusing on anti-aging interventions at the population level.

    PubMed

    Hartwig, Fernando Pires; Bertoldi, Daniel; Larangeira, Martin; Wagner, Mônica Silveira

    2014-02-01

    Most human populations are undergoing a demographic transition regarding their age structure. This transition is reflected in chronic non-communicable diseases featuring among the main contributors to burden of disease. Considering that the aging process is a major risk factor for such conditions, understanding the mechanisms underlying aging and age-related diseases is critical to develop strategies to impact human health at population and/or individual-levels. Two different aspects of aging process (namely, telomere shortening and DNA damage accumulation) were shown to interact in positively impacting mice median survival. However, strategies aimed at translating such knowledge into actual human health benefits have not yet been discussed. In this manuscript, we present potential exposures that are suited for population-level interventions, and contextualize the roles of population (based on behavioral exposures) and individual-level (based on small-molecule administration) anti-aging interventions in different levels of disease prevention. We suggest that exposures such as moderate wine consumption, reducing calorie intake and active lifestyle are potentially useful for primordial and primary prevention, while small-molecules that activate telomerase and/or tumor suppression responses are more suited for secondary and tertiary prevention (although important for primary prevention in specific population subgroups). We also indicate the need of studying the impacts, on aging and age-related diseases, of different combinations of these exposures in well-conducted randomized controlled trials, and propose Mendelian randomization as a valuable alternative to gather information in human populations regarding the effects of potential anti-aging interventions.

  15. Age and site-related patterns of carbon allocation to wood, foliage and roots on reclaimed kaolin mines in Georgia

    SciTech Connect

    Legerski, A.; Hendrick, R.; Ogden, E.

    1996-12-31

    We quantified merchantable stand volume, leaf area indices (LAI), and root densities in twelve Pinus taeda L. forests growing on reclaimed kaolin mines in Georgia. Stands were 11 to 36 yrs old, and formed two productivity classes, Projected wood volume on the poor sites ranged 104 to 142 m{sup 3}/ha and from 164 to 298 on the better sites. LAI was not related to age on either the good or poor sites, LAIs reach their maximal values early in stand development (<12 yrs). Fine roots (0-1 mm) within the upper 1 m were most abundant on the poorer sites. Roots were nearly absent at depths>50 cm in stands aged 14 or less, but neatly equal in density to surface roots in the older stands. Stand age was strongly and negatively related to fine root density on both site types. Densities of larger, more perennial roots (1-2 mm) decreased with stand age on poor sites and increased on good sites. Stand productivity is closely related to LAI, and root densities show that trees allocate more energy into fine, absorbing roots on the poorer sites. Deep fine root densities indicate that trees must explore progressively greater volumes of soil to meet water and nutritional needs in reclaimed soils.

  16. The common fragile site FRA16D gene product WWOX: roles in tumor suppression and genomic stability.

    PubMed

    Aqeilan, Rami I; Abu-Remaileh, Muhannad; Abu-Odeh, Mohammad

    2014-12-01

    The fragile WWOX gene, encompassing the chromosomal fragile site FRA16D, is frequently altered in human cancers. While vulnerable to DNA damage itself, recent evidence has shown that the WWOX protein is essential for proper DNA damage response (DDR). Furthermore, the gene product, WWOX, has been associated with multiple protein networks, highlighting its critical functions in normal cell homeostasis. Targeted deletion of Wwox in murine models suggests its in vivo requirement for proper growth, metabolism, and survival. Recent molecular and biochemical analyses of WWOX functions highlighted its role in modulating aerobic glycolysis and genomic stability. Cumulatively, we propose that the gene product of FRA16D, WWOX, is a functionally essential protein that is required for cell homeostasis and that its deletion has important consequences that contribute to the neoplastic process. This review discusses the essential role of WWOX in tumor suppression and genomic stability and how its alteration contributes to cancer transformation.

  17. Primary Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) of the penis: a report of an extraordinarily unusual site and a literature review of extraskeletal Ewing's sarcoma.

    PubMed

    Ma, Zheng; Brimo, Fadi; Zeizafoun, Nebras

    2013-02-01

    Ewing's sarcomas/primitive neuroectodermal tumors (ES/PNETs) arise from a multipotent progenitor cell and are considered to be of neuroectodermal derivation. Most tumors commonly arise in the skeletal system, which are the classic ES/PNET and occasionally occur in the soft tissue of extraskeletal sites, which are named extraskeletal Ewing's sarcomas (EES/PNET). This study reports a case of a 28-year-old man with primary EES/PNET of the penis.

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

    PubMed

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

    1995-12-01

    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

  19. 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

  20. Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance.

    PubMed

    Ge, Zhishen; Liu, Shiyong

    2013-09-07

    Self-assembled nanostructures of amphiphilic and double hydrophilic block copolymers have been increasingly utilized as potent polymeric nanocarriers of therapeutic drugs, genes, bioactive molecules, and imaging/contrast agents due to improved water solubility, bioavailability, and extended blood circulation duration. Though passive and active targeted drug delivery strategies have long been proposed to promote desirable drug accumulation specifically at the disease sites, the introduction of stimuli-responsiveness into self-assembled block copolymer nanocarriers can additionally lead to controlled/triggered release of therapeutic/imaging agents into target pathological tissues and cells, with concomitant advantages of enhanced delivery efficiency and therapeutic efficacy. Appropriately designed stimuli-responsive block copolymer assemblies can exhibit chemical structure transformation, microstructural rearrangement and inversion, or even disassembly into unimers or smaller ones under external stimuli such as pH, temperature, ion strength, redox potential, light, electric, and magnetic fields, and specific bioactive molecules and metabolites. Compared to normal tissues, pathological sites such as tumor tissues typically exhibit vascular abnormalities, weak acidity (~pH 6.8), abnormal temperatures, over-expressed proteins and enzymes, hypoxia, high levels of metabolites and reactive small molecule species, etc. Moreover, upon cellular uptake, drug-loaded polymeric nanocarriers will be subjected to intracellular pH gradients (pH 5.9-6.2 in early endosomes and pH 5.0-5.5 in late endosomes and lysosomes) and redox and H2O2 gradients within different cell organelles and the cytosol. Thus, block copolymer nanocarriers responsive to the above described bio-relevant stimuli or biochemical signals characteristic of pathologic tissues and cells will provide an alternative type of "active targeting" strategy, which can be utilized to further boost therapeutic efficacy and

  1. Nitrogen removal pathway of anaerobic ammonium oxidation in on-site aged refuse bioreactor.

    PubMed

    Wang, Chao; Zhao, Youcai; Xie, Bing; Peng, Qing; Hassan, Muhammad; Wang, Xiaoyuan

    2014-05-01

    The nitrogen removal pathways and nitrogen-related functional genes in on-site three-stage aged refuse bioreactor (ARB) treating landfill leachate were investigated. It was found that on average 90.0% of CODCr, 97.6% of BOD5, 99.3% of NH4(+)-N, and 81.0% of TN were removed with initial CODCr, BOD5, NH4(+)-N, and TN concentrations ranging from 2323 to 2754, 277 to 362, 1237 to 1506, and 1251 to 1580 mg/L, respectively. Meanwhile, the functional genes amoA, nirS and anammox 16S rRNA gene were found to coexist in every bioreactor, and their relative proportions in each bioreactor were closely related to the pollutant removal performance of the corresponding bioreactor, which indicated the coexistence of multiple nitrogen removal pathways in the ARB. Detection of anammox expression proved the presence of the anammox nitrogen removal pathway during the process of recirculating mature leachate to the on-site ARB, which provides important information for nitrogen management in landfills.

  2. 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.

  3. 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

  4. Identification of Optimal Insertion Site in Recombinant Newcastle Disease Virus (rNDV) Vector Expressing Foreign Gene to Enhance Its Anti-Tumor Effect

    PubMed Central

    Pan, Ziye; He, Jinjiao; Rasoul, Lubna M.; Liu, Yunye; Che, Ruixiang; Ding, Yun; Guo, Xiaocheng; Yang, Jiarui; Zou, Dehua; Zhang, Hua; Li, Deshan; Cao, Hongwei

    2016-01-01

    Recombinant Newcastle disease virus (rNDV) is tumor selective and intrinsically oncolytic, which has been developed as a vector to express exogenous genes to enhance its oncolytic efficacy. Our previous studies found that insertion sites of foreign gene in rNDV vector affected its expression and anti-tumor activities. However, the optimal insertion site for foreign genes remains unknown. In this study, we inserted the enhanced green fluorescence protein (EGFP) and IL2 genes into four different intergenic regions of the rNDV using reverse genetics technology. Recombinants rNDV-EGFPs and rNDV-IL2s were successfully rescued, which displayed the similar growth kinetics with parental virus. Both EGFP mRNA and protein levels were most abundant in HepG2 cells, when EGFP gene was inserted between the NP/P site of the rNDV. Similarly, the IL-2 expressed by HepG2 cells infected with rNDV-IL2 was highest, when IL2 was inserted into NP/P site. To test whether these rNDVs that express higher foreign genes could induce stronger anti-tumor response, we treated the H22-oxter-tumor-bearing C57BL/6J mice with rNDV-IL2s and then examined the oncolytic efficacy. The results showed that rNDV-IL2-NP/P had the strongest inhibition of murine hepatoma carcinoma tumors. The splenocytes isolated from the mice treated with rNDV-IL2-NP/P reached the highest degrees of CD4+ T and CD8+ T cells. In addition, animals’ survival rate in rNDV-IL2-NP/P-treated group was higher than that of other groups. Taken together, these results demonstrate that NP and P gene junction in rNDV is the optimal insertion site for foreign genes expression to enhance rNDV’s anti-tumor effects. PMID:27736965

  5. 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.

  6. 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.

  7. IMMMUNOPHENOTYPE OF SPONTANEOUS HEMATOLYMPHOID TUMORS OCCURRING IN YOUNG AND AGING FEMALE CD-1 MICE

    PubMed Central

    Rehg, Jerold E.; Rahija, Richard; Bush, Dorothy; Bradley, Alys; Ward, Jerrold M.

    2015-01-01

    A few reports indicated the incidence of hematolymphoid neoplasms in old CD-1 mice, but the cellular lineage of CD-1 mouse neoplasms has not be published. In this study, immunohistochemistry (IHC) was used to characterize the cellular lineage of spontaneous hematolymphoid neoplasms arising in young female CD-1 mice used as health monitoring sentinels and aging female CD-1 mice used as controls in 80 wk carcinogenesis studies. Lymphoblastic lymphomas of T-cell and B-cell lineage were common in mice 12 mo or less of age, whereas a wide range of non-lymphoblastic B-cell lymphomas and lymphoblastic T-cell lymphomas were common in mice > 12 mo old. Renal hyaline droplets positive for lysozyme were observed in aged mice with a histiocytic-associated large B-cell lymphoma (HA-BCL) and a myeloid leukemia. Endogenous ecotropic MuLV genes have been recovered from CD-1 mice, but MuLV protein expression has not been previously demonstrated. We reported for the first time the expression of MuLV protein by IHC in lymphomas and some normal tissues of both young and aging CD-1 mice. This report should help to differentiate spontaneous lymphomas and leukemias in CD-1 mice from those induced by chemicals and other methods. PMID:26224701

  8. Is cancer a metabolic rebellion against host aging? In the quest for immortality, tumor cells try to save themselves by boosting mitochondrial metabolism.

    PubMed

    Ertel, Adam; Tsirigos, Aristotelis; Whitaker-Menezes, Diana; Birbe, Ruth C; Pavlides, Stephanos; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2012-01-15

    Aging drives large systemic reductions in oxidative mitochondrial function, shifting the entire body metabolically towards aerobic glycolysis, a.k.a, the Warburg effect. Aging is also one of the most significant risk factors for the development of human cancers, including breast tumors. How are these two findings connected? One simplistic idea is that cancer cells rebel against the aging process by increasing their capacity for oxidative mitochondrial metabolism (OXPHOS). Then, local and systemic aerobic glycolysis in the aging host would provide energy-rich mitochondrial fuels (such as L-lactate and ketones) to directly "fuel" tumor cell growth and metastasis. This would establish a type of parasite-host relationship or "two-compartment tumor metabolism", with glycolytic/oxidative metabolic-coupling. The cancer cells ("the seeds") would flourish in this nutrient-rich microenvironment ("the soil"), which has been fertilized by host aging. In this scenario, cancer cells are only trying to save themselves from the consequences of aging, by engineering a metabolic mutiny, through the amplification of mitochondrial metabolism. We discuss the recent findings of Drs. Ron DePinho (MD Anderson) and Craig Thomspson (Sloan-Kettering) that are also consistent with this new hypothesis, linking cancer progression with metabolic aging. Using data mining and bioinformatics approaches, we also provide key evidence of a role for PGC1a/NRF1 signaling in the pathogenesis of (1) two-compartment tumor metabolism, and (2) mitochondrial biogenesis in human breast cancer cells.

  9. Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice

    PubMed Central

    Huang, Hu; Liu, Ying; Wang, Lei; Li, Wen

    2017-01-01

    The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features. White and yellow spots, which look like drusen in humans, were identified with fundscopic examination. Drusen-like sub-RPE deposits with dome-shaped morphology were characterized on the sections. RPE vacuolization, swelling, and sub-RPE basal deposits were illustrated with light and transmission electron microscope (TEM). TEM further illustrated degenerated and disorganized RPE basal infoldings, phagosomes and melanosomes inside RPE, as well as abnormal photoreceptor outer segments. Lipofuscin granules and lipid droplets in the subretinal space, RPE, and choroid were revealed with fluorescence microscope and oil-red-O staining. Increased IgG in RPE/choroid were determined with Western blots (WB). WB and immunofluorescence staining determined RPE zona occuldens (ZO)-1 protein reduction and abnormal subcellular localization. TUNEL staining, outer nuclear layer (ONL) measurement and electroretinogram (ERG) recording indicated that photoreceptors underwent apoptosis, degeneration, and functional impairment. Additionally, spontaneous neovascularization (NV)-like lesions develop in the subretinal space of aged Cxcr5-/- mice. The underlying mechanisms are associated with increased subretinal F4/80+ immune cells, some of which contain RPE marker RPE65, and up-regulation of the multifunctional cytokine tumor necrosis factor-alpha (TNF-α) in RPE/choroid and retina. These findings suggest that Cxcr5 itself may be involved in the protection of RPE and

  10. Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice.

    PubMed

    Huang, Hu; Liu, Ying; Wang, Lei; Li, Wen

    2017-01-01

    The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features. White and yellow spots, which look like drusen in humans, were identified with fundscopic examination. Drusen-like sub-RPE deposits with dome-shaped morphology were characterized on the sections. RPE vacuolization, swelling, and sub-RPE basal deposits were illustrated with light and transmission electron microscope (TEM). TEM further illustrated degenerated and disorganized RPE basal infoldings, phagosomes and melanosomes inside RPE, as well as abnormal photoreceptor outer segments. Lipofuscin granules and lipid droplets in the subretinal space, RPE, and choroid were revealed with fluorescence microscope and oil-red-O staining. Increased IgG in RPE/choroid were determined with Western blots (WB). WB and immunofluorescence staining determined RPE zona occuldens (ZO)-1 protein reduction and abnormal subcellular localization. TUNEL staining, outer nuclear layer (ONL) measurement and electroretinogram (ERG) recording indicated that photoreceptors underwent apoptosis, degeneration, and functional impairment. Additionally, spontaneous neovascularization (NV)-like lesions develop in the subretinal space of aged Cxcr5-/- mice. The underlying mechanisms are associated with increased subretinal F4/80+ immune cells, some of which contain RPE marker RPE65, and up-regulation of the multifunctional cytokine tumor necrosis factor-alpha (TNF-α) in RPE/choroid and retina. These findings suggest that Cxcr5 itself may be involved in the protection of RPE and

  11. Expansion and Activation of CD103(+) Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition.

    PubMed

    Salmon, Hélène; Idoyaga, Juliana; Rahman, Adeeb; Leboeuf, Marylène; Remark, Romain; Jordan, Stefan; Casanova-Acebes, Maria; Khudoynazarova, Makhzuna; Agudo, Judith; Tung, Navpreet; Chakarov, Svetoslav; Rivera, Christina; Hogstad, Brandon; Bosenberg, Marcus; Hashimoto, Daigo; Gnjatic, Sacha; Bhardwaj, Nina; Palucka, Anna Karolina; Brown, Brian D; Brody, Joshua; Ginhoux, Florent; Merad, Miriam

    2016-04-19

    Large numbers of melanoma lesions develop resistance to targeted inhibition of mutant BRAF or fail to respond to checkpoint blockade. We explored whether modulation of intratumoral antigen-presenting cells (APCs) could increase responses to these therapies. Using mouse melanoma models, we found that CD103(+) dendritic cells (DCs) were the only APCs transporting intact antigens to the lymph nodes and priming tumor-specific CD8(+) T cells. CD103(+) DCs were required to promote anti-tumoral effects upon blockade of the checkpoint ligand PD-L1; however, PD-L1 inhibition only led to partial responses. Systemic administration of the growth factor FLT3L followed by intratumoral poly I:C injections expanded and activated CD103(+) DC progenitors in the tumor, enhancing responses to BRAF and PD-L1 blockade and protecting mice from tumor rechallenge. Thus, the paucity of activated CD103(+) DCs in tumors limits checkpoint-blockade efficacy and combined FLT3L and poly I:C therapy can enhance tumor responses to checkpoint and BRAF blockade.

  12. The Anti-Aging and Tumor Suppressor Protein Klotho Enhances Differentiation of a Human Oligodendrocytic Hybrid Cell Line

    PubMed Central

    Chen, Ci-Di; Liang, Jennifer; Hixson, Kathryn; Zeldich, Ella; Abraham, Carmela R.

    2016-01-01

    Klotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats, and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here, we examined the signaling pathways induced by Klotho in MO3.13, a human oligodendrocytic hybrid cell line. We show that exogenous Klotho affects the ERK and Akt signaling pathways, decreases the proliferative abilities and enhances differentiation of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80 % of the differentially expressed genes being downregulated. Using gene set enrichment analysis, we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging, and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain and other malignancies. PMID:24907942

  13. Breastfeeding and nutrition to 2 years of age and risk of childhood acute lymphoblastic leukemia and brain tumors.

    PubMed

    Greenop, Kathryn R; Bailey, Helen D; Miller, Margaret; Scott, Rodney J; Attia, John; Ashton, Lesley J; Downie, Peter; Armstrong, Bruce K; Milne, Elizabeth

    2015-01-01

    Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is known of their etiology. In 2 nationwide case-control studies we investigated whether breastfeeding, age of food introduction, or early diet are associated with the risk of these cancers. Cases aged 0-14 years were identified from Australian pediatric oncology units between 2003 and 2007 (ALL) and 2005 and 2010 (CBT) and population-based controls through nationwide random-digit dialing. Mothers completed questionnaires giving details of infant feeding up to the age of 2 yr. Data from 322 ALL cases, 679 ALL controls, 299 CBT cases, and 733 CBT controls were analysed using unconditional logistic regression. Breastfeeding was associated with a reduced risk of ALL [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.32, 0.84), regardless of duration. Introduction of artificial formula within 14 days of birth was positively associated with ALL (OR = 1.57, 95% CI: 1.03, 2.37), as was exclusive formula feeding to 6 mo (OR = 1.81, 95% CI: 1.07, 3.05). No associations were seen between breastfeeding or formula use and risk of CBT. Our results suggest that breastfeeding and delayed introduction of artificial formula may reduce the risk of ALL but not CBT.

  14. 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.

  15. 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.

  16. Changes in sex and non-sex hormones and distribution of erythrocyte antigens in reproductive age women with tumors of body of uterus in Adjara.

    PubMed

    Nakashidze, I; Kotrikadze, N; Diasamidze, A; Nagervadze, M; Ramishvili, L

    2013-04-01

    The aim the research was to study the hormonal state of reproductive age women with tumors of body of uterus. The quantitative changes of sex steroid hormones: progesterone (P), estradiol (E), testosterone (T), gonadotropine -Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were investigated. Distribution of ABO blood group antigens and Rh-Hr systems genetic variants in the blood of women living in Adjara Region was also studied. For study was used reproductive age women's blood with benign (fibromioma) and malignant (endometrial cancer) tumors of body of uterus (the middle age was 20-45 years). The determination of hormones was made by the enzymatic analysis method (ELAIZA). For the research of blood groups, were used the immunoserologic methods. The study have revealed that in blood of reproductive age women with benign and malignant tumors of body of uterus, level of estradiol was increased while levels of progesterone and testosterone were sharply reduced. Amount of Follicle-stimulating hormone and Luteinizing hormone were also increased. It's significant that, both hormones were sharply increased in case of cancer of body of uterus, in comparison with control group and benign tumor. According to distribution of ABO blood group phenotypes - O (I) phenotypic group of ABO system has its highest frequency in blood of women with cancer of body of uterus. Cancer of body of uterus is associated with O (I) phenotypic groups; benign tumor of body of uterus - with A(II) and AB(IV) phenotypic groups. Women with cc and EE genetic variants of Rh-Hr system have sensitivity to the development of benign and malignant tumors of body of uterus; women with ee genetic variant have lower sensitivity towards body of uterus cancer and sharply expressed sensitivity to uterus benign tumors. In women with malignant tumors of body of uterus the frequency of distribution of Rh-Hr system CC genetic variant was sharply reduced.

  17. Causal Therapy of Breast Cancer Irrelevant of Age, Tumor Stage and 
ER-Status: Stimulation of Estrogen Signaling Coupled With Breast 
Conserving Surgery

    PubMed Central

    Suba, Zsuzsanna

    2016-01-01

    Abstract: Background Results of long-term studies justify that the rate of breast cancer recurrence and tumor-related mortality remains quite unpredictable, regardless of the use of any current therapeutic measures. Objective Since the application of standard therapies, such as surgery, radiation, chemotherapy and antiestrogen administration does not work as might be expected; our therapeutic practice requires thorough rethinking. Method Published long-term therapeutic results on breast cancer cases were analyzed in correlation with stage at diagnosis, ER-status of tumors and patients’ age. The effectiveness of current therapeutic measures was also compared by estimating the rate of tumor-free survival, breast cancer recurrence and breast cancer-specific mortality. Results Diagnosis and treatment of breast cancer at an early stage cannot improve the rate of tumor-free survival. Poor differentiation of tumors, ER-negativity in particular, defines poor prognosis even after applying aggressive therapies. In patients treated with in situ breast cancer, the recurrence-rate of invasive tumor increased directly with ageing irrespective of tumor size or ER-status at diagnosis. Women who underwent lumpectomy without adjuvant radiation or chemotherapy exhibited significantly better overall and breast cancer specific survival rates than those receiving mastectomy, regardless of stage and ER-status of tumors. Antiestrogen treatment exhibited unforeseeable effectiveness even on targeted ER-positive tumors. Recent patents propose the detection of ESR1-gene amplification or restoration of ER-alpha expression for prediction of effective antiestrogen treatment, suggesting a crucial inhibitory role of estrogen-signaling against tumor-growth. Conclusion Estradiol-induced upregulation of estrogen signaling coupled with sparing of the estrogen-rich mammary fatpad are the most effective strategies against breast cancer. PMID:27087654

  18. High-dose Chemotherapy With Autologous Stem Cell Rescue in Saudi Children Less Than 3 Years of Age With Embryonal Brain Tumors.

    PubMed

    Alsultan, Abdulrahman; Alharbi, Musa; Al-Dandan, Sadeq; Bayoumi, Yasser; Alharbi, Talal; Alsudairy, Reem; Alomari, Ali; Aljamaan, Khalid; Musleh, Othman; Alharbi, Qasim; Jarrar, Mohammed

    2015-04-01

    High-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) has been used in children under the age of 3 years with embryonal brain tumors to avoid or delay the use of radiation. We reviewed the medical records of 10 Saudi children less than 3 years of age with embryonal brain tumors who underwent HDC/ASCR. All 10 patients underwent surgical resection followed by 3 to 5 cycles of induction chemotherapy and 1 to 3 cycles of HDC/ASCR using carboplatin and thiotepa. Isotretinoin was used as a maintenance therapy in 4 patients. Five patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumors, 1 had an embryonal tumor with abundant neuropil and true rosettes, and 1 had pineoblastoma. The median age of the patients was 1.9 years. A total of 19 HDC/ASCR procedures were performed. Radiotherapy (RT) was administered to 5 patients after HDC/ASCR and as a salvage therapy in 1 patient. The progression-free survival rate was 50% at 1 year and at 2 years, with a median follow-up of 24 months. All 5 patients with medulloblastoma are still alive without evidence of disease, but the other patients died secondary to tumor progression. This experience suggests that strategies combining myeloablative chemotherapy and autologous stem cell rescue appear to be feasible for children with embryonal brain tumors in the Middle East.

  19. 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

  20. 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.

  1. 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. PMID:27635226

  2. Site-Specific Characteristics of Bone Marrow Mesenchymal Stromal Cells Modify the Effect of Aging on the Skeleton.

    PubMed

    Wang, Xing; Zou, Xuan; Zhao, Jing; Wu, Xia; E, Lingling; Feng, Lin; Wang, Dongsheng; Zhang, Guilan; Xing, Helin; Liu, Hongchen

    2016-03-15

    Bone is a self-renewing tissue. Bone marrow mesenchymal stromal cells (BMSCs) are located in the adult skeleton and are believed to be involved in the maintenance of skeletal homeostasis throughout life. With increasing age, the ability of the skeleton to repair itself decreases, possibly due to the reduced functional capacity of BMSCs. Recent evidence has suggested the existence of at least two populations of BMSCs with different embryonic origins that cannot be interchanged during stem cell recruitment: craniofacial BMSCs (neural crest origin) and appendicular BMSCs (mesoderm origin). Questions arise as to whether the site-specific characteristics alter the effect of aging on the skeleton. In this study, the effects of biological aging on human BMSCs were compared with BMSCs derived from the craniofacial bone versus those derived from the appendicular skeleton. The phenotype, proliferation, and functional characteristics (osteogenic differentiation, cytokine secretion, and bone formation in vivo) of the BMSCs were investigated. The results demonstrated that the proliferative capacity and osteogenic differentiation of the BMSCs decrease significantly with age both in vitro and in vivo. For age-matched groups, the osteogenic differentiation capacity of alveolar BMSCs was higher than that of femoral BMSCs in the middle-aged and old groups, while there was no significant difference for the young groups. Compared with old alveolar BMSCs, old femoral BMSCs had a significantly longer population doubling time, a smaller colony-forming population, and less bone formation in vivo, while there was no significant difference for the young and middle-aged groups. Distinct differences in the expression of cytokine factors were also found. In conclusion, human BMSCs display an age-related decrease in functional capacity, and embryonic origins may play a critical role in mediating the aging rate of BMSCs. These data provide novel insights into the skeletal site

  3. 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.

  4. 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.

  5. 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

  6. [Combined spinal epidural anesthesia during endoprosthetic surgeries for bone tumors in old-age children].

    PubMed

    Matinian, N V; Saltanov, A I

    2005-01-01

    Thirty-five patients (ASA II-III) aged 12 to 17 years, diagnosed as having osteogenic sarcoma and Ewing's sarcoma localizing in the femur and tibia, were examined. Surgery was performed as sectoral resection of the affected bone along with knee joint endoprosthesis. Surgical intervention was made under combined spinal and epidural anesthesia (CSEA) with sedation, by using the methods for exact dosing of propofol (6-4 mg/kg x h). During intervention, a child's respiration remains is kept spontaneous with oxygen insufflation through a nasal catheter. CSEA was performed in two-segmental fashion. The epidural space was first catheterized. After administration of a test dose, 0.5% marcaine spinal was injected into dermatomas below the subarachnoidal space, depending on body weight (3.0-4.0 ml). Sensory blockade developed following 3-5 min and lasted 90-120 min, thereafter a local anesthetic (bupivacaine) or its mixture plus promedole was epidurally administered. ??Anesthesia was effective in all cases, motor blockade. During surgery, there was a moderate arterial hypotension that did not require the use of vasopressors. The acid-alkali balance suggested the adequacy of spontaneous respiration. The only significant complication we observed was atony of the bladder that requires its catheterization till the following day. An epidural catheter makes it possible to effect adequate postoperative analgesia.

  7. A relationship to survival is seen by combining the factors of mismatch repair status, tumor location and age of onset in colorectal cancer patients

    PubMed Central

    Li, Pan; Xiao, Zhitao; Braciak, Todd A.; Ou, Qingjian; Chen, Gong; Oduncu, Fuat S.

    2017-01-01

    Background The progression of colorectal cancer (CRC) may differ depending on the location of the tumor and the age of onset of the disease. Previous studies also suggested that the molecular basis of CRC varies with tumor location, which could affect the clinical management of patients. Therefore, we performed survival analysis looking at different age groups and mismatch repair status (MMR) of CRC patients according to primary tumor location in an attempt to identify subgroups of CRC that might help in the prognosis of disease. Methods A group of 2233 patients operated on to remove their CRC tumors were analyzed (521 with right colon cancer, 740 with left colon cancer and 972 with rectal cancer). The expression of four MMR genes was assessed by immunohistochemistry (IHC), independent of clinical criteria. From the data collected, a predictive model for overall survival (OS) could be constructed for some associations of tumor location and age of onset using Kaplan-Meier, logistic and Cox regression analysis. Results When tumor location was considered as the lone factor, we found no statistical difference in overall survival (OS) between right cancer (68%), left cancer (67%) or rectal cancer tumor locations (71%) (HR: 1.17, 95%CI (confidence interval): 0.97–1.43, P = 0.057). When age of onset was considered, middle age (40–59 years) and older (60–85 years) patients were found to have higher OS than younger onset cancer (20–39 years) patients (69% vs 71% vs 59%, HR: 1.07, 95% confidence interval (CI): 0.91–1.25, P = 0.008). When both age of onset and tumor location were considered in combination as disease factors, we found that the subgroup of patients with left colon cancer from middle age (69%) and older (67%) aged patients had higher OS than younger (54%) patients (HR: 0.89, 95%CI: 0.68–1.16, P = 0.048). However in patients with right colon cancers, we found no statistical difference is OS between younger, middle age or older grouped patients (60% vs

  8. Meckel Diverticulum Harboring a Rare Gastrointestinal Stromal Tumor

    PubMed Central

    Berry, Andrew C.; Nakshabendi, Rahman; Kanar, Ozdemir; Hamer, Sean

    2017-01-01

    Background: Tumors within a Meckel diverticulum are a rare complication observed in only 0.5%-3.2% of symptomatic cases. The majority of tumors are benign, but some malignant tumors, such as gastrointestinal stromal tumors (GISTs) can occur. Case Report: We report the case of a 48-year-old female who presented with severe abdominal pain and nausea and was found to have a GIST arising from a Meckel diverticulum. Conclusion: The differential diagnosis of a pelvic mass in a middle-aged female presenting with gastrointestinal symptoms must remain broad. With an atypical presentation site, distinguishing benign tumors from malignant tumors such as GISTs is of paramount importance. PMID:28331460

  9. The anti-tumor drug bleomycin preferentially cleaves at the transcription start sites of actively transcribed genes in human cells.

    PubMed

    Murray, Vincent; Chen, Jon K; Galea, Anne M

    2014-04-01

    The genome-wide pattern of DNA cleavage at transcription start sites (TSSs) for the anti-tumor drug bleomycin was examined in human HeLa cells using next-generation DNA sequencing. It was found that actively transcribed genes were preferentially cleaved compared with non-transcribed genes. The 143,600 identified human TSSs were split into non-transcribed genes (82,596) and transcribed genes (61,004) for HeLa cells. These transcribed genes were further split into quintiles of 12,201 genes comprising the top 20, 20-40, 40-60, 60-80, and 80-100 % of expressed genes. The bleomycin cleavage pattern at highly transcribed gene TSSs was greatly enhanced compared with purified DNA and non-transcribed gene TSSs. The top 20 and 20-40 % quintiles had a very similar enhanced cleavage pattern, the 40-60 % quintile was intermediate, while the 60-80 and 80-100 % quintiles were close to the non-transcribed and purified DNA profiles. The pattern of bleomycin enhanced cleavage had peaks that were approximately 200 bp apart, and this indicated that bleomycin was identifying the presence of phased nucleosomes at TSSs. Hence bleomycin can be utilized to detect chromatin structures that are present at actively transcribed genes. In this study, for the first time, the pattern of DNA damage by a clinically utilized cancer chemotherapeutic agent was performed on a human genome-wide scale at the nucleotide level.

  10. Dating stratified settlement sites at Kom K and Kom W: Fifth millennium BCE radiocarbon ages for the Fayum Neolithic

    NASA Astrophysics Data System (ADS)

    Wendrich, W.; Taylor, R. E.; Southon, J.

    2010-04-01

    The earliest evidence of the use of domesticated plants, a traditional hallmark of Neolithic societies in the ancient Near East, first appears in Egypt in archaeological sites in the Fayum depression. Due to wind erosion often resulting in deflation of sediments in this region, stratified sites containing organic materials are rare and the depositional contexts of some earlier 14C measurements on Fayum Neolithic materials are not precisely documented. We report the results of 29 AMS-based 14C determinations on charcoal recovered from stratified contexts in two Fayum Neolithic village sites, Kom K and Kom W. These data assign a mid-5th millennium BCE age to these sites and permit an estimate of the length of their occupation to be approximately three centuries.

  11. 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…

  12. 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 , ...

  13. 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.

  14. Tumor Suppressor and Aging Biomarker p16INK4a Induces Cellular Senescence without the Associated Inflammatory Secretory Phenotype*

    PubMed Central

    Coppé, Jean-Philippe; Rodier, Francis; Patil, Christopher K.; Freund, Adam; Desprez, Pierre-Yves; Campisi, Judith

    2011-01-01

    Cellular senescence suppresses cancer by preventing the proliferation of cells that experience potentially oncogenic stimuli. Senescent cells often express p16INK4a, a cyclin-dependent kinase inhibitor, tumor suppressor, and biomarker of aging, which renders the senescence growth arrest irreversible. Senescent cells also acquire a complex phenotype that includes the secretion of many cytokines, growth factors, and proteases, termed a senescence-associated secretory phenotype (SASP). The SASP is proposed to underlie age-related pathologies, including, ironically, late life cancer. Here, we show that ectopic expression of p16INK4a and another cyclin-dependent kinase inhibitor, p21CIP1/WAF1, induces senescence without a SASP, even though they induced other features of senescence, including a stable growth arrest. Additionally, human fibroblasts induced to senesce by ionizing radiation or oncogenic RAS developed a SASP regardless of whether they expressed p16INK4a. Cells induced to senesce by ectopic p16INK4a expression lacked paracrine activity on epithelial cells, consistent with the absence of a functional SASP. Nonetheless, expression of p16INK4a by cells undergoing replicative senescence limited the accumulation of DNA damage and premature cytokine secretion, suggesting an indirect role for p16INK4a in suppressing the SASP. These findings suggest that p16INK4a-positive cells may not always harbor a SASP in vivo and, furthermore, that the SASP is not a consequence of p16INK4a activation or senescence per se, but rather is a damage response that is separable from the growth arrest. PMID:21880712

  15. 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.

  16. 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

  17. Effect of ageing of human serum albumin in vitro on surface hydrophobicity and binding sites of metronidazole

    NASA Astrophysics Data System (ADS)

    Równicka-Zubik, J.; Sułkowska, A.; Dubas, M.; Pożycka, J.; Maciążek-Jurczyk, M.; Bojko, B.; Sułkowski, W. W.

    2011-05-01

    The fluorescence characteristic of the "alkaline-ageing" process was performed. The quenching of the aged form of human serum albumin (AHSA) fluorescence by acrylamide (Ac) was smaller than that of native HSA, in contrast to the negatively charged anion iodide quencher. The comparison of quenching of fluorescence probes ANS and DNSA bound to aged and native forms of HSA allows for the conclusion that "alkaline-ageing process" causes an increase of hydrophobicity within the binding site located in subdomain IIA. This conclusion was confirmed by the F coefficients calculated for the emission fluorescence spectra of A- and N-forms of HSA excited at 295 nm and 275 nm which show that the increase of hydrophobicity is more significant within tyrosyl than within tryptophanyl residues. The binding constants metronidazole-HSA as well as the number of the class of binding sites were determined by the use of the Scatchard and Klotz-plot analysis. Ageing of HSA causes an increase of the quenching constant determined from the Stern-Volmer equation for λex 275 nm. However ageing does not affect the K Q value for λex 295 nm. The influence of ageing of human serum albumin on its surface hydrophobicity was also studied with the use of 8-anilino-1-naphthalenesulfonic acid (ANS) as the fluorescence probe. At the ANS fluorescence excitation wavelength λex 360 nm the change in surface hydrophobicity is not observed for both N- and A-forms of HSA. The increase of surface hydrophobicity of the A-form in comparison with that of the native form at λex 295 nm indicates that within subdomain IIA an alteration of HSA conformation takes place.

  18. 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

  19. 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

  20. 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.

  1. Site-specific oxidation at GG and GGG sequences in double-stranded DNA by benzoyl peroxide as a tumor promoter.

    PubMed

    Kawanishi, S; Oikawa, S; Murata, M; Tsukitome, H; Saito, I

    1999-12-21

    Benzoyl peroxide (BzPO), a free-radical generator, has tumor-promoting activity. As a method for approaching the mechanism of tumor promoter function, the ability of oxidative DNA damage by BzPO was investigated by using (32)P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and c-Ha-ras-1 protooncogene. BzPO induced piperidine-labile sites at the 5'-site guanine of GG and GGG sequences of double-stranded DNA in the presence of Cu(I), whereas the damage occurred at single guanine residues of single-stranded DNA. Both methional and dimethyl sulfoxide (DMSO) inhibited DNA damage induced by BzPO and Cu(I), but typical hydroxyl radical ((*)OH) scavengers, superoxide dismutase (SOD) and catalase, did not inhibit it. On the other hand, H(2)O(2) induced piperidine-labile sites at cytosine and thymine residues of double-stranded DNA in the presence of Cu(I). Phenylhydrazine, which is known to produce phenyl radicals, induced Cu(I)-dependent damage at thymine residues but not at guanine residues. These results suggest that the BzPO-derived reactive species causing DNA damage is different from (*)OH and phenyl radicals generated from benzoyloxyl radicals. BzPO/Cu(I) induced 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in double-stranded DNA more effectively than that in single-stranded DNA. Furthermore, we observed that BzPO increased the amount of 8-oxodG in human cultured cells. Consequently, it is concluded that benzoyloxyl radicals generated by the reaction of BzPO with Cu(I) may oxidize the 5'-guanine of GG and GGG sequences in double-stranded DNA to lead to 8-oxodG formation and piperidine-labile guanine lesions, and the damage seems to be relevant to the tumor-promoting activity of BzPO.

  2. Somatic SNPs of the BRCA2 gene at the fragments encoding RAD51 binding sites of canine mammary tumors.

    PubMed

    Ozmen, O; Kul, S; Risvanli, A; Ozalp, G; Sabuncu, A; Kul, O

    2017-01-30

    Mammary tumors are the most common tumor type both in women and in female dogs. In women, heritable breast cancers have been linked mutations in the breast cancer susceptibility gene BRCA2 and it contains eight BRC repeats in exon 11 that bind to RAD51. In this study, we investigated the sequence variations of BRC1-BRC8 and C-terminus of canine BRCA2 gene. From a total of 64 canine patients with mammary tumors, 31 mammary tumors with benign and malign carcinomas and the 3 normal mammary glands were used for the study. In this study, 19 SNPs of exon 11 of BRCA2 in canine mammary tumors were detected for the first time. The c.2383A>C (T1425P) SNP was found to be the most probable disease-associated nsSNP. Our findings suggest that T1425P variation in BRC3 to be the most probable disease-associated nsSNP and may affect RAD51 binding strength.

  3. 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...

  4. 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.

  5. Blinded comparator study of immunohistochemical analysis versus a 92-gene cancer classifier in the diagnosis of the primary site in metastatic tumors.

    PubMed

    Weiss, Lawrence M; Chu, Peiguo; Schroeder, Brock E; Singh, Veena; Zhang, Yi; Erlander, Mark G; Schnabel, Catherine A

    2013-03-01

    Accurate tumor classification is fundamental to inform predictive biomarker testing and optimize therapy. Gene expression-based tests are proposed as diagnostic aids in cases with uncertain diagnoses. This study directly compared the diagnostic accuracy of IHC analysis versus molecular classification using a 92-gene RT-PCR assay for determination of the primary tumor site. This prospectively defined blinded study of diagnostically challenging cases included 131 high-grade, primarily metastatic tumors. Cases were reviewed and reference diagnoses established through clinical correlation. Blinded FFPE sections were evaluated by either IHC/morphology analysis or the 92-gene assay. The final analysis included 122 cases. The 92-gene assay demonstrated overall accuracy of 79% (95% CI, 71% to 85%) for tumor classification versus 69% (95% CI, 60% to 76%) for IHC/morphology analysis (P = 0.019). Mean IHC use was 7.9 stains per case (median, 8; range, 2 to 15). IHC/morphology analysis accuracy was 79%, 80%, and 46% when 1 to 6 (n = 42), 7 to 9 (n = 41), and >9 (n = 39) IHC stains were used, respectively, versus 81%, 85%, and 69%, respectively, with the 92-gene assay. Results from this blinded series of high-grade metastatic cases demonstrate superior accuracy with the 92-gene assay versus standard-of-care IHC analysis and strongly support the diagnostic utility of molecular classification in difficult-to-diagnose metastatic cancer.

  6. Long-term administration of Wilms tumor-1 peptide vaccine in combination with gemcitabine causes severe local skin inflammation at injection sites.

    PubMed

    Soeda, Atsuko; Morita-Hoshi, Yuriko; Kaida, Miho; Wakeda, Takako; Yamaki, Yuni; Kojima, Yasushi; Ueno, Hideki; Kondo, Shunsuke; Morizane, Chigusa; Ikeda, Masafumi; Okusaka, Takuji; Heike, Yuji

    2010-12-01

    The skin toxicity of vaccine therapy at injection sites is generally limited to Grades 1-2 due to the nature of their function. We experienced two cases of severe and prolonged local adverse effects in 25 patients following a Phase I study of gemcitabine and Wilms tumor-1 peptide vaccine mixed with incomplete Freund's adjuvant for inoperable pancreatic or biliary tract cancer. These patients requested to continue the treatment after the study period; however, in the course of compassionate use, they developed unacceptable local skin reactions and terminated their vaccine treatment. One patient (human leukocyte antigen, A0201, 3 mg) developed Grade 3 ulceration at the 10th vaccination and another (human leukocyte antigen, A2402, 1 mg) developed Grade 2 indulation and fibrosis at the 16th vaccination. Skin toxicity occurred at 6.4-8.4 months and continued for several months after the final vaccination during gemcitabine treatment. In these cases, activation or induction of Wilms tumor-1-specific T lymphocytes was not apparent in the peripheral blood despite their severe local reactions. Therefore, we need to monitor patients for late-onset, severe and long-lasting skin reactions at injection sites in Wilms tumor-1 cancer vaccine therapy, particularly for combination treatment with gemcitabine.

  7. Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens

    PubMed Central

    Pita-López, María Luisa; Pera, Alejandra; Solana, Rafael

    2016-01-01

    Human natural killer (NK)-like CD8+ T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8+ T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8+ T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8+KIR+ T-cells, innate CD8+ T-cells, CD8+CD28−KIR+ T-cells or NKT-like CD8+CD56+ cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8+ T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8+ T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8+ T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation (“adaptation”) of the NK-like CD8+ T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity. PMID:28066426

  8. Adaptive Memory of Human NK-like CD8(+) T-Cells to Aging, and Viral and Tumor Antigens.

    PubMed

    Pita-López, María Luisa; Pera, Alejandra; Solana, Rafael

    2016-01-01

    Human natural killer (NK)-like CD8(+) T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8(+) T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8(+) T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8(+)KIR(+) T-cells, innate CD8(+) T-cells, CD8(+)CD28(-)KIR(+) T-cells or NKT-like CD8(+)CD56(+) cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8(+) T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8(+) T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8(+) T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation ("adaptation") of the NK-like CD8(+) T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity.

  9. 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.

  10. Site Specific Discrete PEGylation of 124I-Labeled mCC49 Fab′ Fragments Improves Tumor MicroPET/CT Imaging in Mice

    PubMed Central

    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.

    2014-01-01

    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-dPEG12-(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 (124I) 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

  11. 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

  12. 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…

  13. Expression of Ulex europaeus agglutinin I lectin-binding sites in squamous cell carcinomas and their absence in basal cell carcinomas. Indicator of tumor type and differentiation.

    PubMed

    Heng, M C; Fallon-Friedlander, S; Bennett, R

    1992-06-01

    Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte.

  14. 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

  15. 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

  16. 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

  17. 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 .

  18. 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.

  19. Bone injury and late giant-cell tumor occurrence: a possible relation. A case report.

    PubMed

    De Nayer, P P; Delloye, C; Malghem, J

    1987-09-01

    A giant-cell tumor of the upper end of the fibula, five years after a documented bone injury at the same site is reported. The histologic diagnosis was corroborated by the patient's age, tumor localization, radiologic and pathologic aspects. The role of a bone injury as a promoting factor in the development of this tumor is discussed. The tumoral occurrence as a reactive process to trauma in this case may not be ruled out.

  20. 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.

  1. 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

  2. Tumor Suppressor PDCD4 Represses Internal Ribosome Entry Site-Mediated Translation of Antiapoptotic Proteins and Is Regulated by S6 Kinase 2

    PubMed Central

    Liwak, Urszula; Thakor, Nehal; Jordan, Lindsay E.; Roy, Rajat; Lewis, Stephen M.; Pardo, Olivier E.; Seckl, Michael

    2012-01-01

    Apoptosis can be regulated by extracellular signals that are communicated by peptides such as fibroblast growth factor 2 (FGF-2) that have important roles in tumor cell proliferation. The prosurvival effects of FGF-2 are transduced by the activation of the ribosomal protein S6 kinase 2 (S6K2), which increases the expression of the antiapoptotic proteins X chromosome-linked Inhibitor of Apoptosis (XIAP) and Bcl-xL. We now show that the FGF-2–S6K2 prosurvival signaling is mediated by the tumor suppressor programmed cell death 4 (PDCD4). We demonstrate that PDCD4 specifically binds to the internal ribosome entry site (IRES) elements of both the XIAP and Bcl-xL messenger RNAs and represses their translation by inhibiting the formation of the 48S translation initiation complex. Phosphorylation of PDCD4 by activated S6K2 leads to the degradation of PDCD4 and thus the subsequent derepression of XIAP and Bcl-xL translation. Our results identify PDCD4 as a specific repressor of the IRES-dependent translation of cellular mRNAs (such as XIAP and Bcl-xL) that mediate FGF-2–S6K2 prosurvival signaling and provide further insight into the role of PDCD4 in tumor suppression. PMID:22431522

  3. 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

  4. 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.

  5. GIS-based landform classification of Bronze Age archaeological sites on Crete Island

    PubMed Central

    Argyriou, Athanasios V.; Teeuw, Richard M.; Sarris, Apostolos

    2017-01-01

    Various physical attributes of the Earth’s surface are factors that influence local topography and indirectly influence human behaviour in terms of habitation locations. The determination of geomorphological setting plays an important role in archaeological landscape research. Several landform types can be distinguished by characteristic geomorphic attributes that portray the landscape surrounding a settlement and influence its ability to sustain a population. Geomorphometric landform information, derived from digital elevation models (DEMs), such as the ASTER Global DEM, can provide useful insights into the processes shaping landscapes. This work examines the influence of landform classification on the settlement locations of Bronze Age (Minoan) Crete, focusing on the districts of Phaistos, Kavousi and Vrokastro. The landform classification was based on the topographic position index (TPI) and deviation from mean elevation (DEV) analysis to highlight slope steepness of various landform classes, characterizing the surrounding landscape environment of the settlements locations. The outcomes indicate no interrelationship between the settlement locations and topography during the Early Minoan period, but a significant interrelationship exists during the later Minoan periods with the presence of more organised societies. The landform classification can provide insights into factors favouring human habitation and can contribute to archaeological predictive modelling. PMID:28222134

  6. GIS-based landform classification of Bronze Age archaeological sites on Crete Island.

    PubMed

    Argyriou, Athanasios V; Teeuw, Richard M; Sarris, Apostolos

    2017-01-01

    Various physical attributes of the Earth's surface are factors that influence local topography and indirectly influence human behaviour in terms of habitation locations. The determination of geomorphological setting plays an important role in archaeological landscape research. Several landform types can be distinguished by characteristic geomorphic attributes that portray the landscape surrounding a settlement and influence its ability to sustain a population. Geomorphometric landform information, derived from digital elevation models (DEMs), such as the ASTER Global DEM, can provide useful insights into the processes shaping landscapes. This work examines the influence of landform classification on the settlement locations of Bronze Age (Minoan) Crete, focusing on the districts of Phaistos, Kavousi and Vrokastro. The landform classification was based on the topographic position index (TPI) and deviation from mean elevation (DEV) analysis to highlight slope steepness of various landform classes, characterizing the surrounding landscape environment of the settlements locations. The outcomes indicate no interrelationship between the settlement locations and topography during the Early Minoan period, but a significant interrelationship exists during the later Minoan periods with the presence of more organised societies. The landform classification can provide insights into factors favouring human habitation and can contribute to archaeological predictive modelling.

  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. Sleep fragmentation and sepsis differentially impact blood-brain barrier integrity and transport of tumor necrosis factor-α in aging.

    PubMed

    Opp, Mark R; George, Amrita; Ringgold, Kristyn M; Hansen, Kim M; Bullock, Kristin M; Banks, William A

    2015-11-01

    The factors by which aging predisposes to critical illness are varied, complex, and not well understood. Sepsis is considered a quintessential disease of old age because the incidence and mortality of severe sepsis increases in old and the oldest old individuals. Aging is associated with dramatic changes in sleep quality and quantity and sleep increasingly becomes fragmented with age. In healthy adults, sleep disruption induces inflammation. Multiple aspects of aging and of sleep dysregulation interact via neuroimmune mechanisms. Tumor necrosis factor-α (TNF), a cytokine involved in sleep regulation and neuroimmune processes, exerts some of its effects on the CNS by crossing the blood-brain barrier (BBB). In this study we examined the impact of sepsis, sleep fragmentation, and aging on BBB disruption and TNF transport into brain. We used the cecal ligation and puncture (CLP) model of sepsis in young and aged mice that were either undisturbed or had their sleep disrupted. There was a dichotomous effect of sepsis and sleep disruption with age: sepsis disrupted the BBB and increased TNF transport in young mice but not in aged mice, whereas sleep fragmentation disrupted the BBB and increased TNF transport in aged mice, but not in young mice. Combining sleep fragmentation and CLP did not produce a greater effect on either of these BBB parameters than did either of these manipulations alone. These results suggest that the mechanisms by which sleep fragmentation and sepsis alter BBB functions are fundamentally different from one another and that a major change in the organism's responses to those insults occurs with aging.

  9. Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth: understanding the aging and cancer connection.

    PubMed

    Balliet, Renee M; Capparelli, Claudia; Guido, Carmela; Pestell, Timothy G; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Whitaker-Menezes, Diana; Chiavarina, Barbara; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2011-12-01

    Increasing chronological age is the most significant risk factor for cancer. Recently, we proposed a new paradigm for understanding the role of the aging and the tumor microenvironment in cancer onset. In this model, cancer cells induce oxidative stress in adjacent stromal fibroblasts. This, in turn, causes several changes in the phenotype of the fibroblast including mitochondrial dysfunction, hydrogen peroxide production, and aerobic glycolysis, resulting in high levels of L-lactate production. L-lactate is then transferred from these glycolytic fibroblasts to adjacent epithelial cancer cells and used as "fuel" for oxidative mitochondrial metabolism.  Here, we created a new pre-clinical model system to directly test this hypothesis experimentally. To synthetically generate glycolytic fibroblasts, we genetically-induced mitochondrial dysfunction by knocking down TFAM using an sh-RNA approach.  TFAM is mitochondrial transcription factor A, which is important in functionally maintaining the mitochondrial respiratory chain. Interestingly, TFAM-deficient fibroblasts showed evidence of mitochondrial dysfunction and oxidative stress, with the loss of certain mitochondrial respiratory chain components, and the over-production of hydrogen peroxide and L-lactate. Thus, TFAM-deficient fibroblasts underwent metabolic reprogramming towards aerobic glycolysis.  Most importantly, TFAM-deficient fibroblasts significantly promoted tumor growth, as assayed using a human breast cancer (MDA-MB-231) xenograft model. These increases in glycolytic fibroblast driven tumor growth were independent of tumor angiogenesis. Mechanistically, TFAM-deficient fibroblasts increased the mitochondrial activity of adjacent epithelial cancer cells in a co-culture system, as seen using MitoTracker. Finally, TFAM-deficient fibroblasts also showed a loss of caveolin-1 (Cav-1), a known breast cancer stromal biomarker. Loss of stromal fibroblast Cav-1 is associated with early tumor recurrence, metastasis

  10. 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.

  11. Radiofrequency Ablation of Liver Tumors

    MedlinePlus

    ... Site Index A-Z Radiofrequency Ablation (RFA) of Liver Tumors Radiofrequency ablation (RFA) is a treatment that ... of Liver Tumors? What is Radiofrequency Ablation of Liver Tumors? Radiofrequency ablation, sometimes referred to as RFA, ...

  12. DMD and IL1RAPL1: two large adjacent genes localized within a common fragile site (FRAXC) have reduced expression in cultured brain tumors.

    PubMed

    McAvoy, S; Ganapathiraju, S; Perez, D S; James, C D; Smith, D I

    2007-01-01

    Common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. Spanning the center of the two most frequently expressed CFS regions, FRA3B (3p14.3) and FRA16D (16q23.2), are the 1.5 Mb FHIT gene and the 1.0 Mb WWOX gene. These genes are frequently deleted and/or altered in many different cancers. Both FHIT and WWOX have been demonstrated to function as tumor suppressors, both in vitro and in vivo. A number of other large CFS genes have been identified and are also frequently inactivated in multiple cancers. Based on these data, several additional very large genes were tested to determine if they were derived from within CFS regions, but DCC and RAD51L1 were not. However, the 2.0 Mb DMD gene and its immediately distal neighbor, the 1.8 Mb IL1RAPL1 gene are CFS genes contained within the FRAXC CFS region (Xp21.2-->p21.1). They are abundantly expressed in normal brain but were dramatically underexpressed in every brain tumor cell line and xenograft (derived from an intracranial model of glioblastoma multiforme) examined. We studied the expression of eleven other large CFS genes in the same panel of brain tumor cell lines and xenografts and found reduced expression of multiple large CFS genes in these samples. In this report we show that there is selective loss of specific large CFS genes in different cancers that does not appear to be mediated by the relative instability within different CFS regions. Further, the inactivation of multiple large CFS genes in xenografts and brain tumor cell lines may help to explain why this type of cancer is highly aggressive and associated with a poor clinical outcome.

  13. Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma.

    PubMed

    Honda, Yuki; Otsuka, Atsushi; Ono, Sachiko; Yamamoto, Yosuke; Seidel, Judith A; Morita, Satoshi; Hirata, Masahiro; Kataoka, Tatsuki R; Takenouchi, Tatsuya; Fujii, Kazuyasu; Kanekura, Takuro; Okubo, Yuko; Takahashi, Kenzo; Yanagi, Teruki; Hoshina, Daichi; Hata, Hiroo; Abe, Riichiro; Fujimura, Taku; Funakoshi, Takeru; Yoshino, Koji; Masuzawa, Mamiko; Amoh, Yasuyuki; Tanaka, Ryota; Fujisawa, Yasuhiro; Honda, Tetsuya; Kabashima, Kenji

    2017-01-01

    Cutaneous angiosarcoma (CAS) is a malignant sarcoma with poor prognosis. Programmed cell death-1 (PD-1)/programmed cell death-1 ligand-1 (PD-L1) expression reflects antitumor immunity, and is associated with patient prognosis in various cancers. The purpose of this study is to investigate the relationship between PD-1/PD-L1 expression and CAS prognosis. CAS cases (n = 106) were immunohistochemically studied for PD-L1 and PD-1 expression, and the correlation with patient prognosis was analyzed. PD-L1 expression was assessed by flow cytometry on three CAS cell lines with or without IFNγ stimulation. A total of 30.2% of patients' samples were positive for PD-L1, and 17.9% showed a high infiltration of PD-1-positive cells. Univariate analysis showed a significant relationship between a high infiltration of PD-1-positive cells with tumor site PD-L1 expression and favorable survival in stage 1 patients (p = 0.014, log-rank test). Multivariable Cox-proportional hazard regression analysis also showed that patients with a high infiltration of PD-1-positive cells with tumor site PD-L1 expression were more likely to have favorable survival, after adjustment with possible confounders (hazard ratio (HR) = 0.38, p = 0.021, 95% confidence interval (CI) 0.16-0.86). Immunofluorescence staining of CAS samples revealed that PD-L1-positive cells were adjacent to PD-1-positive cells and/or tumor stroma with high IFNγ expression. In vitro stimulation with IFNγ increased PD-L1 expression in two out of three established CAS cell lines. Our results suggest that PD-1/PD-L1 expression is related to CAS progression, and the treatment with anti-PD-1 antibodies could be a new therapeutic option for CAS.

  14. Comparison of the effectiveness of high and low LET radiations for the proportion of survivals with liver tumors at every age in (C57BL/6N x C3H/HeN) F1 mice.

    PubMed

    Nitta, Yumiko; Satoh, Kenichi; Suga, Shinji; Endo, Satoru; Nitta, Kohsaku

    2006-07-01

    To investigate the late effects of neutrons at the energy below 1 MeV on the liver carcinogenesis as a function of age, one-week old mice were exposed to 1.0 Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV) or 137Cs gamma rays. Survival and carcinogenesis were examined by 18 months of age. Following radiation, tumor incidences in liver, Harderian gland, lung, ovary and pituitary gland were compared. The proportion of the lifespan with liver tumors exposed to neutrons to that exposed to gamma rays was calculated as a function of age. Survival rates among the three groups exposed to neutrons of different energies were not significantly different from one another but shorter than those treated with gamma rays for both sexes. With regard to liver tumor incidence evaluated at 18 months of age, the effectiveness of neutrons to gamma rays was 2.54 for females, and 2.08 for males by the factor. Levels of estrogen in the serum were similar between mice bearing liver tumors and those devoid of tumors. In conclusion, all three energies of neutrons induced similar effectiveness with respect to liver carcinogenicity. Proportions of the lifespan with liver tumors of neutron-exposed to gamma-exposed were shorter in females than males along with ages over 12 months. To obtain this factor at every age contributed for the evaluation of the biological effectiveness of radiations with the parameter of tumor incidence and latency simultaneously.

  15. Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation

    SciTech Connect

    Plougastel, B.; Zucman, J.; Peter, M.; Thomas, G.; Delattre, O. )

    1993-12-01

    The EWS gene has been identified based on its location at the chromosome 22 breakpoint of the t(11;22)(q24;q12) translocation that characterizes Ewing sarcoma and related neuroectodermal tumors. The EWS gene spans about 40 kb of DNA and is encoded by 17 exons. The nucleotide sequence of the exons is identical to that of the previously described cDNA. The first 7 exons encode the N-terminal domain of EWS, which consists of a repeated degenerated polypeptide of 7 to 12 residues rich in tyrosine, serine, threonine, glycine, and glutamine. Exons 11, 12, and 13 encode the putative RNA binding domain. The three glycine- and arginine-rich motifs of the gene are mainly encoded by exons 8-9, 14, and 16. The DNA sequence in the 5[prime] region of the gene has features of a CpG-rich island and lacks canonical promoter elements, such as TATA and CCAAT consensus sequences. Positions of the chromosome 22 breakpoints were determined for 19 Ewing tumors. They were localized in introns 7 or 8 in 18 cases and in intron 10 in 1 case. 26 refs., 5 figs.

  16. 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.

  17. Insights on organic aerosol aging and the influence of coal combustion at a regional receptor site of Central Eastern China

    NASA Astrophysics Data System (ADS)

    Hu, W. W.; Hu, M.; Yuan, B.; Jimenez, J. L.; Tang, Q.; Peng, J. F.; Hu, W.; Shao, M.; Wang, M.; Zeng, L. M.; Wu, Y. S.; Gong, Z. H.; Huang, X. F.; He, L. Y.

    2013-04-01

    In order to understand the aging and processing of organic aerosols (OA), an intensive field campaign (Campaign of Air Pollution at Typical Coastal Areas In Eastern China, CAPTAIN) was conducted in March-April at a receptor site (Changdao Island) in Central Eastern China. Multiple fast aerosol and gas measurement instruments were used during the campaign, including a high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was applied to measure mass concentrations and non-refractory chemical components of submicron particles (PM1nr). The average mass concentration of PM1 (PM1nr + black carbon) was 47 ± 36 μg m-3 during the campaign and showed distinct variation depending on back trajectories and their overlap with source regions. Organic aerosol (OA) is the largest component of PM1 (30%), followed by nitrate (28%), sulfate (19%), ammonium (15%), black carbon (6%), and chloride (3%). Four OA components were resolved by Positive Matrix Factorization (PMF) of the high-resolution spectra, including low-volatility oxygenated organic aerosol (LV-OOA), semi-volatile oxygenated OA (SV-OOA), hydrocarbon-like OA (HOA) and a coal combustion OA (CCOA), reported here for the first time. The mass spectrum of CCOA has high abundance of fragments from polycyclic aromatic hydrocarbons (PAHs) (m/z 128, 152, 178 etc.). The average atomic ratio of oxygen to carbon in OA (O/C) at Changdao is 0.59, which is comparable to other field studies reported at locations downwind of large pollution sources, indicating the oxidized nature of most OA during the campaign. The evolution of OA elemental composition in the Van Krevelen diagram (H/C vs. O/C) shows a slope of -0.63, however, the OA influenced by coal combution exhibits a completely different evolution that appears dominated by physical mixing. The aging of organic aerosols vs. with photochemical age was investigated. It is shown that OA/ΔCO, as well as LV-OOA/ΔCO and SV-OOA/ΔCO, positively correlated with

  18. Insights on organic aerosol aging and the influence of coal combustion at a regional receptor site of central eastern China

    NASA Astrophysics Data System (ADS)

    Hu, W. W.; Hu, M.; Yuan, B.; Jimenez, J. L.; Tang, Q.; Peng, J. F.; Hu, W.; Shao, M.; Wang, M.; Zeng, L. M.; Wu, Y. S.; Gong, Z. H.; Huang, X. F.; He, L. Y.

    2013-10-01

    In order to understand the aging and processing of organic aerosols (OA), an intensive field campaign (Campaign of Air Pollution at Typical Coastal Areas IN Eastern China, CAPTAIN) was conducted March-April at a receptor site (a Changdao island) in central eastern China. Multiple fast aerosol and gas measurement instruments were used during the campaign, including a high resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) that was applied to measure mass concentrations and non-refractory chemical components of submicron particles (PM1nr). The average mass concentration of PM1(PM1nr+black carbon) was 47 ± 36 μg m-3 during the campaign and showed distinct variation, depending on back trajectories and their overlap with source regions. Organic aerosol (OA) is the largest component of PM1 (30%), followed by nitrate (28%), sulfate (19%), ammonium (15%), black carbon (6%), and chloride (3%). Four OA components were resolved by positive matrix factorization (PMF) of the high-resolution spectra, including low-volatility oxygenated organic aerosol (LV-OOA), semi-volatile oxygenated OA (SV-OOA), hydrocarbon-like OA (HOA) and a coal combustion OA (CCOA). The mass spectrum of CCOA had high abundance of fragments from polycyclic aromatic hydrocarbons (PAHs) (m/z 128, 152, 178, etc.). The average atomic ratio of oxygen to carbon in OA (O / C) at Changdao was 0.59, which is comparable to other field studies reported at locations downwind of large pollution sources, indicating the oxidized nature of most OA during the campaign. The evolution of OA elemental composition in the van Krevelen diagram (H / C vs. O / C) showed a slope of -0.63; however, the OA influenced by coal combustion exhibits a completely different evolution that appears dominated by physical mixing. The aging of organic aerosols vs. photochemical age was investigated. It was shown that OA / ΔCO, as well as LV-OOA / ΔCO and SV-OOA / ΔCO, positively correlated with photochemical age. LV

  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. 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.

  1. Initial excavation and dating of Ngalue Cave: a Middle Stone Age site along the Niassa Rift, Mozambique.

    PubMed

    Mercader, Julio; Asmerom, Yemane; Bennett, Tim; Raja, Mussa; Skinner, Anne

    2009-07-01

    Direct evidence for a systematic occupation of the African tropics during the early late Pleistocene is lacking. Here, we report a record of human occupation between 105-42ka, based on results from a radiometrically-dated cave section from the Mozambican segment of the Niassa (Malawi/Nyasa) Rift called Ngalue. The sedimentary sequence from bottom to top has five units. We concentrate on the so-called "Middle Beds," which contain a Middle Stone Age industry characterized by the use of the discoidal reduction technique. A significant typological feature is the presence of formal types such as points, scrapers, awls, and microliths. Special objects consist of grinders/core-axes covered by ochre. Ngalue is one of the few directly-dated Pleistocene sites located along the biogeographical corridor for modern human dispersals that links east, central, and southern Africa, and, with further study, may shed new light on hominin cave habitats during the late Pleistocene.

  2. miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites.

    PubMed

    Rinnerthaler, Gabriel; Hackl, Hubert; Gampenrieder, Simon Peter; Hamacher, Frank; Hufnagl, Clemens; Hauser-Kronberger, Cornelia; Zehentmayr, Franz; Fastner, Gerd; Sedlmayer, Felix; Mlineritsch, Brigitte; Greil, Richard

    2016-01-26

    For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan(®) Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)(®) microarrays from Agilent(®) was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort.

  3. Use of nano-sized clay crystallites to restore adhesion among tumor and aging stem cells - a molecular simulations approach

    PubMed Central

    Ahmed, Habib-ur-Rehman; Abduljauwad, Sahel N

    2016-01-01

    Adhesion of cells to the ECM is key to the regulation of cellular morphology, migration, proliferation, survival, and differentiation. The decrease in or loss of the cell’s ability of mutual adhesiveness has been considered as one of the specific abnormalities in the surface properties of malignant cells. A change in the association of plasma membrane with cytoskeletal structures also seems to have a close relation with these abnormalities. Similar to the role of adhesions in tumor cells, stem cells’ self-renewal is also tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. This study has demonstrated through molecular simulations the potential use of smectite (Na-montmorillonite) clay crystallites to create adhesions among tumor and stem cells. High electrostatic energies and cohesive energy densities measured in the simulations after the sorption of clay crystallites on cell-cell and cell-ECM complexes validate the concept of using these crystallites for the purposes. As results of this study are quite promising and clay crystallites could be considered as an option to restore adhesions in tumor and stem cells, other confirmatory tests and live cell culture studies are in process for the final validation. PMID:28078181

  4. 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.

  5. 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

  6. 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

  7. Impact of methylenetetrahydrofolate reductase polymorphisms and folate intake on the risk of gastric cancer and their association with Helicobacter pylori infection and tumor site.

    PubMed

    Chen, J; Yuan, L; Duan, Y Q; Jiang, J Q; Zhang, R; Huang, Z J; Xiao, X R

    2014-01-24

    Folic acid and methylenetetrahydrofolate reductase (MTHFR) may both affect the development of human cancer. We conducted a population-based case-control study in a Chinese population to investigate the potential role of folate intake and MTHFR gene polymorphisms in gastric cancer, and their interaction with infection by Helicobacter pylori and tumor location. A total of 767 patients with newly diagnosed gastric cancer and 775 controls were selected for this study. Genotyping of MTHFR C677T and A1298C was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System, and information on folate intake was collected by questionnaire. Compared with the CC genotype of MTHFR C677T, the TT genotype was significantly associated with a decreased risk of gastric cancer when the analysis was adjusted for other potential risk factors. We found a marginal significantly decreased risk of gastric cancer for individuals carrying the T allele [adjusted odds ratio (OR) = 0.83; 95% confidence interval (CI) = 0.65-1.01]. We detected an inverse relationship between folate intake and risk of gastric cancer, and the adjusted ORs (95%CI) for moderate and high folate intake were 0.97 (0.74-1.25) and 0.64 (0.49-0.87), respectively. Moreover, H. pylori infection, folate intake, and location of the tumor showed a significant interaction with the MTHFR C677T polymorphism. Our study suggests a protective role of MTHFR 677TT and high folate intake against gastric cancer, and the effect of the MTHFR C677T genotype may differ by H. pylori infection, folate consumption, and tumor site.

  8. A case report and short review on changing trends in the site of occurrence of adenomatoid odontogenic tumor: Unravelling the past 15 years

    PubMed Central

    Sethi, Sneha; Kumar, Manish; Aggarwal, Pratul; Indra Kumar, H. S.; Sugandhi, Chetan D.; Singh, Silvie

    2016-01-01

    Adenomatoid odontogenic tumor (AOT) is an uncommon benign odontogenic lesion, with debatable histogenesis and variable histopathology. A systematic and diverse insight into the evolution, clinical presentation, histology, and immunohistochemical findings of this lesion is reviewed and presented. We reviewed the data published from 2000 to 2014 of approximately 255 cases that revealed a significant change in the incidence of predominant site involved, in contrast to the findings published by Reichart. We have also included the chronological order of events leading to the coining of the term AOT, which shows the curiosity that has been dedicated to understanding the lesion. Immunohistochemistry is considered to be a hallmark in pathology for learning the molecular pathogenesis and giving a correct final diagnosis. Several markers have been used to investigate and understand this lesion, and a compilation of the findings has been tabulated. PMID:27857774

  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. A high affinity HSF-1 binding site in the 5'-untranslated region of the murine tumor necrosis factor-alpha gene is a transcriptional repressor.

    PubMed

    Singh, Ishwar S; He, Ju-Ren; Calderwood, Stuart; Hasday, Jeffrey D

    2002-02-15

    Tumor necrosis factor-alpha (TNFalpha) is a pivotal early mediator of host defenses that is essential for survival in infections. We previously reported that exposing macrophages to febrile range temperatures (FRT) (38.5-40 degrees C) markedly attenuates TNFalpha expression by causing abrupt and premature cessation of transcription. We showed that this inhibitory effect of FRT is mediated by an alternatively activated repressor form of heat shock factor 1 (HSF-1) and that a fragment of the TNFalpha gene comprising a minimal 85-nucleotide (nt) proximal promoter and the 138-nt 5'-untranslated region (UTR) was sufficient for mediating this effect. In the present study we have used an electrophoretic mobility shift assay (EMSA) to identify a high affinity binding site for HSF-1 in the 5'-UTR of the TNFalpha gene and have used a chromosome immunoprecipitation assay to show that HSF-1 binds to this region of the endogenous TNFalpha gene. Mutational inactivation of this site blocks the inhibitory effect of overexpressed HSF-1 on activity of the minimal TNFalpha promoter (-85/+138) in Raw 264.7 murine macrophages, identifying this site as an HSF-1-dependent repressor. However, the same mutation fails to block repression of a full-length (-1080/+138) TNFalpha promoter construct by HSF-1 overexpression, and HSF-1 binds to upstream sequences in the regions -1080/-845, -533/-196, and -326/-39 nt in EMSA, suggesting that additional HSF-1-dependent repressor elements are present upstream of the minimal -85-nt promoter. Furthermore, although mutation of the HSF-1 binding site in the minimal TNFalpha promoter construct abrogates HSF-1-mediated repression, the same mutation fails to abrogate repression of this construct by high levels of HSF-1 overexpression or exposure to 39.5 degrees C. This suggests that HSF-1 might repress TNFalpha transcription through redundant mechanisms, some of which might not require high affinity binding of HSF-1.

  11. Understanding the diagnostic yield of current endoscopic biopsy for gastric neoplasm: A prospective single-center analysis based on tumor characteristics stratified by biopsy number and site.

    PubMed

    Kwack, Won G; Ho, Won J; Kim, Jae H; Lee, Jin H; Kim, Eo J; Kang, Hyoun W; Lee, Jun K

    2016-07-01

    Although there are general guidelines on endoscopic biopsy for diagnosing gastric neoplasms, they are predominantly based on outdated literature obtained with fiberscopes without analyses specific to tumor characteristics.This study aims to comprehensively characterize the contemporary endoscopic biopsy by determining the diagnostic yield across different lesion morphologies and histological stages, especially exploring how the number and site of biopsy may influence the overall yield.Biopsy samples from suspected gastric neoplasms were collected prospectively from May 2011 to August 2014 in a tertiary care medical center. A standardized methodology was used to obtain a total of 6 specimens from 2 defined sites per lesion. Rate of positive diagnosis based on the biopsy number and site was assessed for specific gastric lesion morphologies and histological stages.A total of 1080 biopsies from 180 pathologically diagnosed neoplastic lesions in 176 patients were obtained during the study. For depressed/ulcerative and polypoid lesions, the yield was already >99% by the fourth biopsy without further gain from additional biopsies. Lower overall yield was observed for infiltrative lesions (57.1% from 4 biopsies). The site of biopsy did not influence the diagnostic yield except for with infiltrative lesions in which biopsies from thickened mucosal folds were of higher yield than erosive regions.Obtaining 4 specimens may be sufficient for accurate diagnosis of a depressed/ulcerative or polypoid gastric lesion regardless of its histological stage. For infiltrative lesions, at least 5 to 6 biopsies per lesion with more representative sampling from thickened mucosal folds may be preferable.

  12. 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.

  13. Age-Specific Gene Expression Signatures for Breast Tumors and Cross-Species Conserved Potential Cancer Progression Markers in Young Women

    PubMed Central

    Colak, Dilek; Nofal, Asmaa; AlBakheet, AlBandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; AL-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Kaya, Namik; Park, Ben H.; Bin Amer, Suad M.

    2013-01-01

    Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross

  14. 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.

  15. Impact of age on access site-related outcomes in 469,983 percutaneous coronary intervention procedures: Insights from the British Cardiovascular Intervention Society.

    PubMed

    Anderson, Simon G; Ratib, Karim; Myint, Phyo K; Keavney, Bernard; Kwok, Chun Shing; Zaman, Azfar; Ludman, Peter F; de Belder, Mark A; Nolan, James; Mamas, Mamas A

    2015-11-15

    We investigate adoption of the TRA in different age groups and study the relationship between age and access site related outcomes in a national cohort of patients undergoing PCI in the UK. Previous studies have reported conflicting data on radial access site adoption between different age groups, with age an independent predictor of failure of procedures undertaken through the radial approach. Age and access site related outcomes (based on transradial (TRA) and transfemoral (TFA) access) were studied in 469,983 PCI procedures undertaken in the UK from 2006 to 2012 in the age groups; <60, 60-<70, 70-<80, and ≥80 in the British Cardiovascular Intervention Society database. We studied access site practice in 469,983 patients who underwent PCI procedures in the United Kingdom. TRA utilization increased from 17.5% to 65.6% in the age group <60, and 16.6% to 54.5% in the age group ≥80 between 2006 and 2012. TRA was independently associated with decreased 30-day mortality in all age groups (<60: OR 0.64; 95% CI 0.54-0.74, P < 0.0001; 60-<70: OR 0.65; 95% CI 0.57-75, P < 0.0001, 70-<80: OR 0.58 (0.52-0.65, P < 0.0001 and ≥80: OR 0.65 (0.57-0.73, P < 0.0001). Adoption of the TRA for PCI has occurred least in older patients in the UK despite similar associations between TRA use and decreased 30-day mortality observed in all age groups.

  16. Methylation of CpG sites in BCL2 major breakpoint region and the increase of BCL2/JH translocation with aging.

    PubMed

    Martin-Guerrero, Idoia; de Prado, Elena; Ardanaz, Maite; Martin-Arruti, Maialen; Garcia-Orad, Cristina; Guerra, Isabel; Ruiz, Irune; Zabalza, Iñaki; Garcia-Orad, Africa

    2015-10-01

    The BCL2 breakage mechanism has been shown to be highly dependent on DNA methylation at the major breakpoint region (MBR) CpG sites. We recently described an increased frequency of BCL2/ JH translocation with aging. It is known that methylation levels change with aging. The present study aimed to determine whether methylation alterations at CpG sites of BCL2 MBR were the cause of increased breakages with aging. We analyzed the methylation levels of three CpG sites on the region by pyrosequencing and studied if methylation levels and/or polymorphisms affecting CpG sites were associated with an increase of translocations. We observed that although the methylation levels of MBR CpG sites were higher in individuals with BCL2/JH translocation, in contrast to our expectations, these levels decreased with the age. Moreover, we show that polymorphisms at those CpG sites leading to absence of methylation seem to be a protective factor for the apparition of translocations.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. CsTNF1, a teleost tumor necrosis factor that promotes antibacterial and antiviral immune defense in a manner that depends on the conserved receptor binding site.

    PubMed

    Li, Mo-fei; Zhang, Jian

    2016-02-01

    Tumor necrosis factor (TNF) is one of the most important cytokines involved in inflammation, apoptosis, cell proliferation, and stimulation of the immune system. The TNF gene has been cloned in teleost fish; however, the in vivo function of fish TNF is essentially unknown. In this study, we report the identification of a TNF homologue, CsTNF1, from tongue sole (Cynoglossus semilaevis) and analysis of its expression and biological effect. CsTNF1 is composed of 242 amino acid residues and possesses a TNF domain and conserved receptor binding sites. Expression of CsTNF1 was detected in a wide range of tissues and up-regulated in a time-dependent manner by experimental challenge with bacterial and viral pathogens. Bacterial infection of peripheral blood leukocytes (PBL) caused extracellular secretion of CsTNF1. Purified recombinant CsTNF1 (rCsTNF1) was able to bind to PBL and stimulate the respiratory burst activity of PBL. In contrast, rCsTNF1M1 and rCsTNF1M2, the mutant CsTNF1 bearing substitutions at the receptor binding site, failed to activate PBL. Fish administered with rCsTNF1, but not with rCsTNF1M1 and rCsTNF1M2, exhibited enhanced expression of IL-1, IL-6, IL-8, IL-27, TLR9 and G3BP in a time-dependent manner and augmented resistance against bacterial and viral infection. These results provide the first evidence that the receptor binding sites are essential to a fish TNF, and that CsTNF1 is involved in the innate immune defense of fish against microbial pathogens.

  3. Bone tumors in a tertiary care hospital of south India: A review 117 cases

    PubMed Central

    Jain, Karun; Sunila; Ravishankar, R.; Mruthyunjaya; Rupakumar, C. S.; Gadiyar, H. B.; Manjunath, G. V.

    2011-01-01

    Background: Bone tumors remain a daunting challenge to orthopedic surgeons. The challenge is heightened in developing countries due to limited diagnostic and therapeutic facilities as well as due to ignorance. The published literature on this subject is sparse in our environment. Objective: To determine the pattern of bone tumors including their relative frequencies, age and sex distributions, anatomical sites of occurrence and clinico-pathological characteristics as seen in a tertiary care hospital of south India. Materials and Methods: This is a retrospective review of all the histologically confirmed bone tumors seen at JSS Medical College and Hospital, Mysore over an 8 year period: 2002 to 2009. Results: A total of 117 patients (aged 5 to 82 years) with a mean of age of 26.87 years were studied. Seventy-six patients (64.96%) were males and 41 (35.04%) were females. The peak age incidence for primary bone tumors was in the age group of 11-20 years and that for metastatic bone tumors was more than 60 years. Sixty-seven (57.26%) of the tumors were benign. Among these, osteochondroma was the most common, accounting for 26 cases (22.22%) followed by Giant cell tumor (24 cases, 20.51%). Osteosarcoma accounted for 35.14% (13 cases) of all the primary malignant tumors in the study. Lower end of femur was the most common site for primary bone tumors and accounted for 30 cases (25.64%) followed by upper end of tibia and fibula (24 cases, 20.51%). The most common site for metastatic bone tumors was upper end of femur including hip joint followed by spine. Conclusion: This study showed that primary bone tumors are mainly benign, occurred predominantly in the second decade of life with a male preponderance. Osteochondroma and osteosarcoma are the most common benign and primary malignant bone tumors, respectively. The most common primary foci for metastatic bone tumor are from the respiratory tract. PMID:22174495

  4. 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

  5. Temporal-spatial distribution of archaeological sites in the Nihewan-Huliu Basin during the Paleolithic-Neolithic and Iron Age in northern China

    NASA Astrophysics Data System (ADS)

    Zhang, J. X.; Wang, X. Y.; Yang, R. X.; Li, X. Z.; Zhang, W.

    2016-11-01

    The Nihewan-Huliu Basin is one of the great regions of human evolution, located in geographical transition zone. This study reveals the temporal-spatial distribution of archaeological sites based on the DEM (Digital Elevation Model) data, and analyses the changes for four periods (Paleolithic-Neolithic transition, Neolithic Age, Bronze Age and Iron Age). These sites expanded from the Sanggan River to the Huliu River and from the central and lower Huliu River to its upper reaches. The population and cultural development in the Nihewan Basin gradually lagged behind the Huliu River Baisin after the Paleolithic-Neolithic transition Age, because of the environmental impacts. The results may aid the understanding and study of the cultural heritage and civilization evolution in northern China.

  6. Renal primitive neuroectodermal tumors.

    PubMed

    Bartholow, Tanner; Parwani, Anil

    2012-06-01

    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  7. CNS and spinal tumors.

    PubMed

    Furtado, Andre D; Panigrahy, Ashok; Fitz, Charles R

    2016-01-01

    Primary CNS tumors consist of a diverse group of neoplasms originating from various cell types in the CNS. Brain tumors are the most common solid malignancy in children under the age of 15 years and the second leading cause of cancer death after leukemia. The most common brain neoplasms in children differ consistently from those in older age groups. Pediatric brain tumors demonstrate distinct patterns of occurrence and biologic behavior according to sex, age, and race. This chapter highlights the imaging features of the most common tumors that affect the child's CNS (brain and spinal cord).

  8. The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes.

    PubMed

    Ksiaa, Feryel; Ziadi, Sonia; Mokni, Moncef; Korbi, Sadok; Trimeche, Mounir

    2010-04-01

    JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P=0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P=0.034) and in the intestinal histological type (P=0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P=0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P=0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.

  9. HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy.

    PubMed

    Campbell, Marcia R; Amin, Dhara; Moasser, Mark M

    2010-03-01

    The human epidermal growth family (HER) of tyrosine kinase receptors underlies the pathogenesis of many types of human cancer. The oncogenic functions of three of the HER proteins can be unleashed through amplification, overexpression, or mutational activation. This has formed the basis for the development of clinically active targeted therapies. However, the third member HER3 is catalytically inactive, not found to be mutated or amplified in cancers, and its role and functions have remained shrouded in mystery. Recent evidence derived primarily from experimental models now seems to implicate HER3 in the pathogenesis of several types of cancer. Furthermore, the failure to recognize the central role of HER3 seems to underlie resistance to epidermal growth factor receptor (EGFR)- or HER2-targeted therapies in some cancers. Structural and biochemical studies have now greatly enhanced our understanding of signaling in the HER family and revealed the previously unrecognized activating functions embodied in the catalytically impaired kinase domain of HER3. This renewed interest and mechanistic basis has fueled the development of new classes of HER3-targeting agents for cancer therapy. However, identifying HER3-dependent tumors presents a formidable challenge and the success of HER3-targeting approaches depends entirely on the development and power of predictive tools.

  10. Aging affect the anti-tumor potential of dendritic cell vaccination, but it can be overcome by co-stimulation with anti-OX40 or anti-4-1BB.

    PubMed

    Sharma, Sanjay; Dominguez, Ana Lucia; Lustgarten, Joseph

    2006-01-01

    It has been well established that there is a decline in immune function with age resulting in a diminished capacity to respond to infections or tumors. Although many studies have demonstrated the efficacy of autologous dendritic cells (DC) vaccines in stimulating an anti-tumor immune response in the young, almost none of these reports consider the effect that aging has on the immune system or test whether DC-vaccination is effective in old hosts. In this study we compared the efficacy of DC-vaccination in young and old mice. Our results showed that DC-vaccination in young animals induced an anti-tumor response resulting in approximately 60% tumor growth inhibition, while minimal protection was observed in old animals. DC vaccination plus rIL-2 further enhanced the anti-tumor response in young animals (approximately 70-75% inhibition), while ineffective in old animals. In contrast, co-administration of anti-OX-40 or anti-4-1BB mAbs vigorously enhanced the anti-tumor immune response in both young (approximately 85-90% inhibition) and old mice (approximately 70-75% inhibition). Our data indicate that although old mice have a decline in immune function, they have the capacity to develop strong anti-tumor responses as long as they are provided with efficient co-stimulation.

  11. [The effect of heavy metal ions and peptide bioregulators on the expression of chromosome fragile sites in the individuals of different age groups and breast cancer patients].

    PubMed

    Dzhokhadze, T A; Ganozishvili, M N; Lezhava, T A

    2008-09-01

    Expression rates of chromosome fragile sites in peripheral blood lymphocytes have been studied in clinically healthy individuals of different age groups (20-38 yrs and 75-86 yrs) and breast cancer patients (8 cases). In individuals with a normal check-up of different age groups the heavy metal (nickel, zinc and cobalt) ions were also examined on their influence on the expression of the fragile sites and the peptide bioregulators (Livagen and Epithalon) were tested on their ability to correct the pattern of expression. Short-term lymphocyte cultures were used as tested material. The analysis showed that the chromosomes of people from young and old age groups differ from each other by the expression pattern of fragile sites - the chromosomes of young individuals were found to be more active by spontaneous formation of fragile sites. They were also sensitive to their induction by heavy metals. Both tested bioregulators lessen heavy metals effect that was statistically reliable only for the young people group. As for the patients with breast cancer general elevated fragility of chromosomes and specific distribution of the fragile sites along the chromosomes were revealed.

  12. Bone tumor

    MedlinePlus

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

  13. The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas.

    PubMed

    Sunaoshi, Masaaki; Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Blyth, Benjamin J; Morioka, Takamitsu; Kaminishi, Mutsumi; Shang, Yi; Nishimura, Mayumi; Shimada, Yoshiya; Tachibana, Akira; Kakinuma, Shizuko

    2015-09-01

    Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear. We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 and at Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus on chromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss was a common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, which lacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after early irradiation (60%) than after young adult-irradiation (30%). Homozygous Pten mutations occurred without DNA copy number change after irradiation starting in infancy, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that while deletions on chromosomes 4 and 11 affecting Cdkn2a and Ikaros are a prominent feature of young adult irradiation-induced T-cell lymphoma, tumors arising after irradiation from infancy suffer a second hit in Pten by mis-segregation or recombination. This is the first report showing an influence of age-at-exposure on genomic alterations of tumor suppressor genes and their relative involvement in radiation-induced T-cell lymphoma. These data are important for considering the risks

  14. 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.

  15. Copper-64-pyruvaldehyde-bis(N(4)-methylthiosemicarbazone) for the prevention of tumor growth at wound sites following laparoscopic surgery: monitoring therapy response with microPET and magnetic resonance imaging.

    PubMed

    Lewis, Jason S; Connett, Judith M; Garbow, Joel R; Buettner, Thomas L; Fujibayashi, Yasuhisa; Fleshman, James W; Welch, Michael J

    2002-01-15

    Laparoscopic colectomy for curable colon cancer may result in the development of abdominal wall implants because of disseminated disease and the favorable environment of the wound site for cell implantation. Injection of disaggregated human GW39 colon cancer cells into the hamster peritoneum represents a model of tumor spillage that may occur during dissection, manipulation, resection, and extraction of tumor during surgery in the clinical setting. Using this well-established animal model, we tested the efficacy of (64)Cu-pyruvaldehyde-bis(N(4)-methylthiosemicarbazone) ((64)Cu-PTSM) in inhibiting tumor cell implantation in trocar wound sites. Anesthetized hamsters had four 5-mm trocars inserted through the anterior abdominal wall. GW39 cells ( approximately 3.2 x 10(4) cells in 0.5 ml) were injected into the peritoneum through a midline incision. Ten min later, hamsters were randomized to receive 5, 3, or 1 mCi of (64)Cu-PTSM through the same midline incision. High-resolution magnetic resonance imaging and microPET were used to monitor tumor volume and morphology after surgery. After 7 weeks, animals were sacrificed, and trocar and midline wounds were harvested for macroscopic and histological analysis. No macroscopic tumor was found in any of the group treated with 5 mCi of (64)Cu-PTSM, whereas 96% of the wound sites in the group treated with saline had macroscopic tumor growth (P < 0.001). This study demonstrates the therapeutic potential of (64)Cu-PTSM in inhibiting cancer cell implantation and growth at doses well below the maximum tolerated dose, with no signs of toxicity to the hamsters.

  16. 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…

  17. Influence of stocking, site quality, stand age, low-severity canopy disturbance, and forest composition on sub-boreal aspen mixedwood carbon stocks

    USGS Publications Warehouse

    Reinikainen, Michael; D’Amato, Anthony W.; Bradford, John B.; Fraver, Shawn

    2014-01-01

    Low-severity canopy disturbance presumably influences forest carbon dynamics during the course of stand development, yet the topic has received relatively little attention. This is surprising because of the frequent occurrence of such events and the potential for both the severity and frequency of disturbances to increase as a result of climate change. We investigated the impacts of low-severity canopy disturbance and average insect defoliation on forest carbon stocks and rates of carbon sequestration in mature aspen mixedwood forests of varying stand age (ranging from 61 to 85 years), overstory composition, stocking level, and site quality. Stocking level and site quality positively affected the average annual aboveground tree carbon increment (CAAI), while stocking level, site quality, and stand age positively affected tree carbon stocks (CTREE) and total ecosystem carbon stocks (CTOTAL). Cumulative canopy disturbance (DIST) was reconstructed using dendroecological methods over a 29-year period. DIST was negatively and significantly related to soil carbon (CSOIL), and it was negatively, albeit marginally, related to CTOTAL. Minima in the annual aboveground carbon increment of trees (CAI) occurred at sites during defoliation of aspen (Populus tremuloides Michx.) by forest tent caterpillar (Malacosoma disstria Hubner), and minima were more extreme at sites dominated by trembling aspen than sites mixed with conifers. At sites defoliated by forest tent caterpillar in the early 2000s, increased sequestration by the softwood component (Abies balsamea (L.) Mill. and Picea glauca (Moench) Voss) compensated for overall decreases in CAI by 17% on average. These results underscore the importance of accounting for low-severity canopy disturbance events when developing regional forest carbon models and argue for the restoration and maintenance of historically important conifer species within aspen mixedwoods to enhance stand-level resilience to disturbance agents and maintain

  18. 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

  19. Comparison of the effects of variable site temperatures and constant incubation temperatures on the biodegradation of petroleum hydrocarbons in pilot-scale experiments with field-aged contaminated soils from a cold regions site.

    PubMed

    Chang, Wonjae; Whyte, Lyle; Ghoshal, Subhasis

    2011-02-01

    Temporal atmospheric temperature changes during summers at sub-Arctic sites often cause periodic fluctuations in shallow landfarm and surface soil temperatures. However, little information is available on the effect of site-relevant variations on biodegradation performance in cold climates. This study compares the rate and extents of biodegradation of petroleum hydrocarbons at variable site temperatures (1-10 °C) representative of summers at a sub-Arctic site reported previously with those obtained under a constant average temperature of 6 °C. The biodegradation was evaluated in pilot-scale landfarming experiments with field-aged petroleum-contaminated soils shipped from Resolution Island (61°30'N, 65°00'W), Nunavut, Canada. Under the variable site temperature conditions biodegradation rate constants of semi- (F2) and non-volatile (F3) hydrocarbon fractions were enhanced by over a factor of two during the 60-d experiment, compared to the constant temperature mode. The decrease in total petroleum hydrocarbons (TPH) under the variable site temperature mode was 55% compared to only 19% under the constant average temperature mode. The enhanced biodegradation is attributable to the non-linear acceleration of microbial activity between 4.7 and 10°C and faster growth of indigenous hydrocarbon-degrading microbial populations. The first-order biodegradation rate constants of 0.018, 0.024 and 0.016 d(-1) for TPH, F2 and F3 fractions at the variable site temperature were in agreement with those determined by an on-site experiment at the same site.

  20. Tuberous sclerosis complex 1: an epithelial tumor suppressor essential to prevent spontaneous prostate cancer in aged mice.

    PubMed

    Kladney, Raleigh D; Cardiff, Robert D; Kwiatkowski, David J; Chiang, Gary G; Weber, Jason D; Arbeit, Jeffrey M; Lu, Zhi Hong

    2010-11-01

    The phosphoinositide 3-kinase (PI3K) pathway regulates mammalian cell growth, survival, and motility and plays a major pathogenetic role in human prostate cancer (PCa). However, the oncogenic contributions downstream of the PI3K pathway made by mammalian target of rapamycin complex 1 (mTORC1)-mediated cell growth signal transduction in PCa have yet to be elucidated in detail. Here, we engineered constitutive mTORC1 activation in prostate epithelium by a conditional genetic deletion of tuberous sclerosis complex 1 (Tsc1), a potent negative regulator of mTORC1 signaling. Epithelial inactivation was not immediately tumorigenic, but Tsc1-deficient mice developed prostatic intraepithelial neoplasia (mPIN) in lateral and anterior prostates by 6 months of age, with increasing disease penetrance over time. Lateral prostate lesions in 16- to 22-month-old mutant mice progressed to two types of more advanced lesions, adenomatous gland forming lesion (Type 1) and atypical glands embedded in massively expanded reactive stroma (Type 2). Both Type 1 and Type 2 lesions contained multiple foci of microinvasive carcinoma. Epithelial neoplastic and atypical stromal lesions persisted despite 4 weeks of RAD001 chemotherapy. Rapalogue resistance was not due to AKT or extracellular signal-regulated kinase 1/2 activation. Expression of the homeobox gene Nkx3.1 was lost in Tsc1-deficient mPIN, and it cooperated with TSC1 loss in mPIN initiation in doubly mutant Tsc1:Nkx3.1 prostatic epithelial knockout mice. Thus, TSC1 inactivation distal to PI3K and AKT activation is sufficient to activate a molecular signaling cascade producing prostatic neoplasia and focal carcinogenesis.

  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. The earliest long-distance obsidian transport: Evidence from the ∼200 ka Middle Stone Age Sibilo School Road Site, Baringo, Kenya.

    PubMed

    Blegen, Nick

    2017-02-01

    This study presents the earliest evidence of long-distance obsidian transport at the ∼200 ka Sibilo School Road Site (SSRS), an early Middle Stone Age site in the Kapthurin Formation, Kenya. The later Middle Pleistocene of East Africa (130-400 ka) spans significant and interrelated behavioral and biological changes in human evolution including the first appearance of Homo sapiens. Despite the importance of the later Middle Pleistocene, there are relatively few archaeological sites in well-dated contexts (n < 10) that document hominin behavior from this time period. In particular, geochemically informed evidence of long-distance obsidian transport, important for investigating expansion of intergroup interactions in hominin evolution, is rare from the Middle Pleistocene record of Africa. The SSRS offers a unique contribution to this small but growing dataset. Tephrostratigraphic analysis of tuffs encasing the SSRS provides a minimum age of ∼200 ka for the site. Levallois points and methods of core preparation demonstrate characteristic Middle Stone Age lithic technologies present at the SSRS. A significant portion (43%) of the lithic assemblage is obsidian. The SSRS obsidian comes from three different sources located at distances of 25 km, 140 km and 166 km from the site. The majority of obsidian derives from the farthest source, 166 km to the south of the site. The SSRS thus provides important new evidence that long-distance raw material transport, and the expansion of hominin intergroup interactions that this entails, was a significant feature of hominin behavior ∼200 ka, the time of the first appearance of H. sapiens, and ∼150,000 years before similar behaviors were previously documented in the region.

  3. Site-specific conjugation of monodispersed DOTA-PEGn to a thiolated diabody reveals the effect of increasing peg size on kidney clearance and tumor uptake with improved 64-copper PET imaging.

    PubMed

    Li, Lin; Crow, Desiree; Turatti, Fabio; Bading, James R; Anderson, Anne-Line; Poku, Erasmus; Yazaki, Paul J; Carmichael, Jenny; Leong, David; Wheatcroft, David; Wheatcroft, Michael P; Raubitschek, Andrew A; Hudson, Peter J; Colcher, David; Shively, John E

    2011-04-20

    Optimal PET imaging of tumors with radiolabeled engineered antibodies requires, among other parameters, matching blood clearance and tumor uptake with the half-life of the engineered antibody. Although diabodies have favorable molecular sizes (50 kDa) for rapid blood clearance (t(1/2) = 30-60 min) and are bivalent, thereby increasing tumor uptake, they exhibit substantial kidney uptake as their major route of clearance, which is especially evident when they are labeled with the PET isotope (64)Cu (t(1/2) = 12 h). To overcome this drawback, diabodies may be conjugated to PEG, a modification that increases the apparent molecular size of the diabody and reduces kidney uptake without adversely affecting tumor uptake or the tumor to blood ratio. We show here that site-specific attachment of monodispersed PEGn of increasing molecular size (n = 12, 24, and 48) can uniformly increase the apparent molecular size of the PEG-diabody conjugate, decrease kidney uptake, and increase tumor uptake, the latter due to the increased residence time of the conjugate in the blood. Since the monodispersed PEGs were preconjugated to the chelator DOTA, the conjugates were able to bind radiometals such as (111)In and (64)Cu that can be used for SPECT and PET imaging, respectively. To allow conjugation of the DOTA-PEG to the diabody, the DOTA-PEG incorporated a terminal cysteine conjugated to a vinyl sulfone moiety. In order to control the conjugation chemistry, we have engineered a surface thiolated diabody that incorporates two cysteines per monomer (four per diabody). The thiolated diabody was expressed and purified from bacterial fermentation and only needs to be reduced prior to conjugation to the DOTA-PEGn-Cys-VS. This novel imaging agent (a diabody with DOTA-PEG48-Cys-VS attached to introduced thiols) gave up to 80%ID/g of tumor uptake with a tumor to blood ratio (T/B) of 8 at 24 h when radiolabeled with (111)In and 37.9% ID/g of tumor uptake (T/B = 8) at 44 h when radiolabeled with

  4. Interpretation of stable isotope, denitrification, and groundwater age data for samples collected from Sandia National Laboratories /New Mexico (SNL/NM) Burn Site Groundwater Area of Concern

    SciTech Connect

    Madrid, V.; Singleton, M. J.; Visser, A.; Esser, B.

    2016-06-02

    This report combines and summarizes results for two groundwater-sampling events (October 2012 and October/November 2015) from the Sandia National Laboratories/New Mexico (SNL/NM) Burn Site Groundwater (BSG) Area of Concern (AOC) located in the Lurance Canyon Arroyo southeast of Albuquerque, NM in the Manzanita Mountains. The first phase of groundwater sampling occurred in October 2012 including samples from 19 wells at three separate sites that were analyzed by the Environmental Radiochemistry Laboratory at Lawrence Livermore National Laboratory as part of a nitrate Monitored Natural Attenuation (MNA) evaluation. The three sites (BSG, Technical Area-V, and Tijeras Arroyo) are shown on the regional hydrogeologic map and described in the Sandia Annual Groundwater Monitoring Report. The first phase of groundwater sampling included six monitoring wells at the Burn Site, eight monitoring wells at Technical Area-V, and five monitoring wells at Tijeras Arroyo. Each groundwater sample was analyzed using the two specialized analytical methods, age-dating and denitrification suites. In September 2015, a second phase of groundwater sampling took place at the Burn Site including 10 wells sampled and analyzed by the same two analytical suites. Five of the six wells sampled in 2012 were resampled in 2015. This report summarizes results from two sampling events in order to evaluate evidence for in situ denitrification, the average age of the groundwater, and the extent of recent recharge of the bedrock fracture system beneath the BSG AOC.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Later Age at Onset of Independent Walking Is Associated with Lower Bone Strength at Fracture-Prone Sites in Older Men.

    PubMed

    Ireland, Alex; Muthuri, Stella; Rittweger, Joern; Adams, Judith E; Ward, Kate A; Kuh, Diana; Cooper, Rachel

    2017-02-09

    Later age at onset of independent walking is associated with lower leg bone strength in childhood and adolescence. However it is unknown whether these associations persist into older age, or whether they are evident at axial (central) or upper limb sites. Therefore we examined walking age obtained at 2y and bone outcomes obtained by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at 60-64y in a nationally-representative cohort study of British people, the MRC National Survey of Health and Development. It was hypothesised that later walking age would be associated with lower bone strength at all sites. Later independent walking age was associated with lower height-adjusted hip (standardised regression coefficients with 95%CI) [-0.179(-0.251,-0.107)], spine [-0.157(-0.232,-0.082)] and distal radius [-0.159(-0.245,-0.073)] bone mineral content (BMC, indicating bone compressive strength) in men (all P < 0.001). Adjustment for covariates partially attenuated these associations, primarily due to lower lean mass and adolescent sporting ability in later walkers. These associations were also evident for a number of hip geometric parameters (including cross-sectional moment of inertia (CSMI), indicating bone bending/torsional strength) assessed by Hip Structural Analysis (HSA) from DXA scans. Similar height-adjusted associations were also observed in women for several hip, spine and upper limb outcomes, although adjustment for fat or lean mass led to complete attenuation for most outcomes, with the exception of femoral shaft CSMI and spine bone area (BA). In conclusion, later independent walking age appears to have a lifelong association with bone strength across multiple skeletal sites in men. These effects may result from direct effects of early life loading on bone growth, and mediation by adult body composition. Results suggest that late walking age may represent a novel risk factor for subsequent low bone strength

  12. Human macrophage inflammatory protein-3alpha/CCL20/LARC/Exodus/SCYA20 is transcriptionally upregulated by tumor necrosis factor-alpha via a non-standard NF-kappaB site.

    PubMed

    Harant, H; Eldershaw, S A; Lindley, I J

    2001-12-14

    The 5'-flanking sequences of the human macrophage inflammatory protein-3alpha/CCL20 gene were cloned and transfected into G-361 human melanoma cells in a luciferase reporter construct. Tumor necrosis factor-alpha (TNF-alpha) treatment stimulated luciferase expression, and promoter truncations demonstrated that TNF-alpha inducibility is conferred by a region between nt -111 and -77, which contains a non-standard nuclear factor-kappaB (NF-kappaB) binding site. The requirement for NF-kappaB was demonstrated as follows: (i) mutations in this NF-kappaB site abrogated TNF-alpha responsiveness; (ii) TNF-alpha activated a construct containing two copies of the CCL20 NF-kappaB binding site; (iii) overexpression of NF-kappaB p65 activated the CCL20 promoter; (iv) NF-kappaB from nuclear extracts of TNF-alpha-stimulated cells bound specifically to this NF-kappaB site.

  13. 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.

  14. 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

  15. Leydig cell tumor

    MedlinePlus

    ... the cells in the testicles that release the male hormone, testosterone . ... seem to be linked to undescended testes . Leydig cell tumors make up a very small number of all testicular tumors. They are most often found in men between 30 and 60 years of age. This ...

  16. Two initiation sites of early detection of colon cancer revealed by localization of pERK1/2 in the nuclei or in aggregates at the perinuclear region of the tumor cells.

    PubMed

    Amsterdam, Abraham; Shezen, Elias; Raanan, Calanit; Schreiber, Letizia; Slilat, Yasmin; Fabrikant, Yakov; Melzer, Ehud; Seger, Rony

    2013-07-01

    We have used human specimens and antibodies to pERK1/2 to detect early development of colon cancer using indirect immunocytochemistry. Two distinct sites were stained; one at the tip of the colon crypts and the other in the stromal tissue associated with the colonic tissue. These foci represent early stages of colon cancer initiation sites as established by enhanced Kirsten Rat Sarcoma Virus (KRAS) and the lack of p53 staining. The enhanced KRAS coincides with the initiation of tumor growth revealed by pERK1/2, both in the tip of the colon crypts, as well as in the stromal initiation site of the colon tumors. Foci of pERK1/2 staining were also detected in 50% of stromal tissue and tips of colon crypts, which were classified as normal tissues, adjacent to the malignant tissue according to general morphology. However, in colon specimens, where no malignancy was observed, no accumulation of pERK1/2 was observed. The staining of pERK1/2 at the stromal foci of the apparently non-malignant tissue appeared as aggregates in the perinuclear region, while in the colon epithelium it appeared in the cell nuclei. In low-grade colon cancer that was still free of induced mutated p53, staining of pERK1/2 was prominent in the cell nuclei, both in the stroma tissue and the tip of the colon crypts. In the intermediate stage, that exhibited significant p53 staining, only a fraction of p53-free tumor cells was labeled with pERK1/2 antibody, while in high-grade tumors, all cells of tumors were labeled with antibodies to p53, but not with antibodies to pERK1/2. We suggest that the down regulation in pERK1/2 labeling is due to the mitogenic capacity of the tumor cells, which are shifted from being driven by nuclear pERK1/2 to mutated p53 expression. We also found that the cytoplasm of low grade tumors was positive for epiregulin, while this labeling decreased in high-grade tumors. We found that the tumors arising from the stroma demonstrated poor structural differentiation, while the

  17. 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.

  18. Changes with age in leucocyte counts, protein and IgG content of lumbar cerebrospinal fluid (CSF) of patients with inflammatory, ischemic, and hemorrhagic diseases or tumors of the central nervous system (CNS).

    PubMed

    Kleine, T O; Weber, L; Zöfel, P

    1988-01-01

    Parameters of blood-brain barrier (BBB) function and of humoral and cellular immune response were determined in lumbar CSF and blood serum samples from 717 patients and statistically compared to "healthy" controls (n = 190). Leucocyte counts (mainly mononuclear cells), total protein and IgG levels in CSF were significantly higher, and prealbumin fraction mostly lower in patients, besides other alterations of protein electrophoresis. Serum fractions (median) of protein electrophoresis were within the reference range. When parameters were correlated with age, a significant increase of total protein of 1.62 mg/dl and of IgG of 0.13 mg/dl per 10 years of age was found in lumbar CSF of controls. Elevated leucocyte counts did not correlate with age of patients, but they increased significantly with age, with respect to controls, to a higher extent in patients with polyneuritis, ischemia and injury; they decreased in patients with brain tumors and polyneuropathy. When compared to controls, elevated total protein levels significantly increased with age only with tumors and injury patients. In multiple sclerosis, IgG increased and beta-globulin fraction decreased significantly in CSF with age. The findings point to age-dependent alterations of BBB and immune response only in some patients groups which were different from those of controls.

  19. On-site removal of antibiotics and antibiotic resistance genes from leachate by aged refuse bioreactor: Effects of microbial community and operational parameters.

    PubMed

    Su, Yinglong; Wang, Jiaxin; Huang, Zhiting; Xie, Bing

    2017-07-01

    The abuse of antibiotics has raised the prevalence of antibiotic resistance, which will pose potential risk to human health. Leachate, generated during the landfill treatment of municipal solid waste, is the important hotspot of the antibiotics and antibiotic resistance genes (ARGs), and no effective on-site treatment has been put forward for preventing ARGs dissemination. Herein, the aged refuse bioreactor was employed to remove antibiotics and ARGs from leachate, and the great removal performance was observed. For the detected antibiotics, the total removal efficiency was about 76.75%, and sulfanilamide and macrolide were removed with high efficiencies (>80%). Among the target ARGs, tetracycline and macrolide resistance genes (tetM, tetQ and ermB) were eliminated with 1.2-2.0 orders of magnitude. The occurrences of ARGs did not correlated with water quality parameters such as COD, total nitrogen, ammonia, nitrate and nitrite, but closely linked to the variations of the bacterial community structure. Redundancy analysis (RDA) indicated the significant correlations between four genera and the distribution of ARGs, which implied that these key genera (including potential pathogens) drove the ARGs removal. Furthermore, the hydraulic loading test confirmed that the aged refuse bioreactor was capable of achieving high removal efficiencies even under shock loading for the higher loading was negative for the proliferations of potential ARGs hosts. This study suggested that aged refuse bioreactor could be a promising way for antibiotics and ARGs on-site removal from leachate.

  20. 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.

  1. Cerebral tumors: specific features in children.

    PubMed

    Koob, M; Girard, N

    2014-10-01

    Brain tumors are the second leading cause of cancer in children. Primary tumors predominate and are of very varied histological types. Their prognosis and treatment depend on the histological type and grade. The diagnostic approach to these includes analysis of the site of the lesion and appearances on computed tomography and MR, and taking account of the age and clinical features of the child. CT is used to diagnose the tumor in an emergency situation. Conventional MR provides a morphological approach and allows a staging assessment to be carried out before surgery. Advanced MR techniques (diffusion-weighted and perfusion imaging, MR spectroscopy) provide further information for the differential diagnosis, presumptive diagnosis of type and grade and to guide biopsy towards the most malignant areas in the lesion.

  2. Giant cell tumor of bone: Multimodal approach

    PubMed Central

    Gupta, AK; Nath, R; Mishra, MP

    2007-01-01

    Background: The clinical behavior and treatment of giant cell tumor of bone is still perplexing. The aim of this study is to clarify the clinico-pathological correlation of tumor and its relevance in treatment and prognosis. Materials and Methods: Ninety -three cases of giant cell tumor were treated during 1980-1990 by different methods. The age of the patients varied from 18-58 yrs with male and female ratio as 5:4. The upper end of the tibia was most commonly involved (n=31), followed by the lower end of the femur(n=21), distal end of radius(n=14), upper end of fibula (n=9), proximal end of femur(n=5), upper end of the humerus(n=3), iliac bone(n=2), phalanx (n=2) and spine(n=1). The tumors were also encountered on uncommon sites like metacarpals (n=4) and metatarsal(n=1). Fifty four cases were treated by curettage and bone grafting. Wide excision and reconstruction was performed in twenty two cases. Nine cases were treated by wide excision while primary amputation was performed in four cases. One case required only curettage. Three inaccessible lesions of ilium and spine were treated by radiotherapy. Results: 19 of 54 treated by curettage and bone grafting showed a recurrence. The repeat curettage and bone grafting was performed in 18 cases while amputation was done in one. One each out of the cases treated by wide excision and reconstruction and wide excision alone recurred. In this study we observed that though curettage and bone grafting is still the most commonly adopted treatment, wide excision of tumor with reconstruction has shown lesser recurrence. Conclusion: For radiologically well-contained and histologically typical tumor, curettage and autogenous bone grafting is the treatment of choice. The typical tumors with radiologically deficient cortex, clinically aggressive tumors and tumors with histological Grade III should be treated by wide excision and reconstruction. PMID:21139762

  3. 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

  4. The cranial analysis of eight skulls from collective grave of the Early Bronze Age Vucedol site (East Slavonia, Croatia).

    PubMed

    Hincak, Zdravka; Cavalli, Fabio; Durman, Aleksandar

    2013-03-01

    The collective grave of the Vucedol culture signed as "grave 3/1985" with skeletons of eight persons, represents the most important burial of this culture on the eponimic site in East Croatia, with several indications of human sacrifice. Anthropological and radiological analysis were performed on crania remains of the individuals, specifically on the skulls of one male and seven females. Nondestructive methods embraced craniometrical analysis, analysis of cranial non-metric traits and multivariate distance analysis, with a help of radiological methods, to detect every distinct anatomical characteristic of the skulls. All methods used in this work tried to present similarities and a possible homogeneity of the analysed individuals.

  5. 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.

    2016-03-02

    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

  6. 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.

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

    PubMed

    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

    2016-02-01

    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 = 0

  8. A seventeenth century mandibular tumor in a North American Indian

    USGS Publications Warehouse

    Kelln, E.E.; McMichael, E.V.; Zimmermann, B.

    1967-01-01

    The oldest tumor so far recorded is believed to have been a hemangioma. It occurred in a bone of a dinosaur’s tail1 and thus considerably antedates the historical period. The oldest known human tumor is much younger, dating back only to the middle of the third century after Christ.1 It was found in the catacombs of Kom el Shougafa in Alexandria, Egypt. This bony tumor (believed to be an osteosarcoma) occurred in the ischium and lower part of the ilium of a pelvic bone. Mention also should be made of a sixteenth century Danish skeleton from Noestried, which had 134 osteomas, and the Bovidal skull, in which there was a sinus osteoma weighing over 12 pounds.2Tumorlike lesions were obviously a problem in Egypt and Assyria, as dissecting instruments and instructions for tumor removal have been found.3 Paleopathologic studies have not yet disclosed bony tumors which occurred in these periods when vigorous embalming techniques were in vogue, and it is possible that only soft-tissue tumors were of concern. Such soft-tissue tumors, of course, would not survive to the present day, and relative accounts of prehistoric neoplasms must be largely based on intraosseus or calcified tumors. Roentgenographic bone patterns, correlated with size, site, age, etc., have led archaeologists and paleopathologists to believe that most surviving ossified tumors are osteomas and osteosarcomas.4

  9. Identification of binding sites on the regulatory A subunit of protein phosphatase 2A for the catalytic C subunit and for tumor antigens of simian virus 40 and polyomavirus.

    PubMed Central

    Ruediger, R; Roeckel, D; Fait, J; Bergqvist, A; Magnusson, G; Walter, G

    1992-01-01

    Protein phosphatase 2A is composed of three subunits: the catalytic subunit C and two regulatory subunits, A and B. The A subunit consists of 15 nonidentical repeats and has a rodlike shape. It is associated with the B and C subunits as well as with the simian virus 40 small T, polyomavirus small T, and polyomavirus medium T tumor antigens. We determined the binding sites on subunit A for subunit C and tumor antigens by site-directed mutagenesis of A. Twenty-four N- and C-terminal truncations and internal deletions of A were assayed by coimmunoprecipitation for their ability to bind C and tumor antigens. It was found that C binds to repeats 11 to 15 at the C terminus of A, whereas T antigens bind to overlapping but distinct regions of the N terminus. Simian virus 40 small T binds to repeats 3 to 6, and polyomavirus small T and medium T bind to repeats 2 to 8. The data suggest cooperativity between C and T antigens in binding to A. This is most apparent for medium T antigen, which can only bind to those A subunit molecules that provide the entire binding region for the C subunit. We infer from our results that B also binds to N-terminal repeats. A model of the small T/medium T/B-A-C complexes is presented. Images PMID:1328865

  10. In vivo magnetic resonance and fluorescence dual imaging of tumor sites by using dye-doped silica-coated iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Jang, Haeyun; Lee, Chaedong; Nam, Gi-Eun; Quan, Bo; Choi, Hyuck Jae; Yoo, Jung Sun; Piao, Yuanzhe

    2016-02-01

    The difficulty in delineating tumor is a major obstacle for better outcomes in cancer treatment of patients. The use of single-imaging modality is often limited by inadequate sensitivity and resolution. Here, we present the synthesis and the use of monodisperse iron oxide nanoparticles coated with fluorescent silica nano-shells for fluorescence and magnetic resonance dual imaging of tumor. The as-synthesized core-shell nanoparticles were designed to improve the accuracy of diagnosis via simultaneous tumor imaging with dual imaging modalities by a single injection of contrast agent. The iron oxide nanocrystals ( 11 nm) were coated with Rhodamine B isothiocyanate-doped silica shells via reverse microemulsion method. Then, the core-shell nanoparticles ( 54 nm) were analyzed to confirm their size distribution by transmission electron microscopy and dynamic laser scattering. Photoluminescence spectroscopy was used to characterize the fluorescent property of the dye-doped silica shell-coated nanoparticles. The cellular compatibility of the as-prepared nanoparticles was confirmed by a trypan blue dye exclusion assay and the potential as a dual-imaging contrast agent was verified by in vivo fluorescence and magnetic resonance imaging. The experimental results show that the uniform-sized core-shell nanoparticles are highly water dispersible and the cellular toxicity of the nanoparticles is negligible. In vivo fluorescence imaging demonstrates the capability of the developed nanoparticles to selectively target tumors by the enhanced permeability and retention effects and ex vivo tissue analysis was corroborated this. Through in vitro phantom test, the core/shell nanoparticles showed a T2 relaxation time comparable to Feridex® with smaller size, indicating that the as-made nanoparticles are suitable for imaging tumor. This new dual-modality-nanoparticle approach has promised for enabling more accurate tumor imaging.

  11. Ear Tumors

    MedlinePlus

    ... Outer Ear Ear Blockages Ear Tumors External Otitis (Swimmer's Ear) Malignant External Otitis Perichondritis Tumors of the ... Outer Ear Ear Blockages Ear Tumors External Otitis (Swimmer's Ear) Malignant External Otitis Perichondritis NOTE: This is ...

  12. 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.

  13. 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.

  14. Updated Magnetostratigraphy of Ice Age Flood Deposits of the Cold Creek Bar at the Hanford Site, Southeastern Washington

    NASA Astrophysics Data System (ADS)

    Pluhar, C. J.; Bjornstad, B. N.; Reidel, S.; Coe, R. S.

    2002-12-01

    Pleistocene cataclysmic flood deposits, informally referred to as the Hanford formation, blanket the Pasco Basin in south-central Washington. This area is a depositional sink for sediments generated by jokulhlaups scouring the channeled scablands during glacial periods. A thick sequence (up to 100 m) of such flood-deposited gravel, sand, and silt underlies much of the USDOE's Hanford Site, within the Pasco Basin. Correlation of these cataclysmic flood deposits is often difficult because of a lack of marker horizons and rapid lateral facies changes. However, paleomagnetic reversals provide an opportunity to establish time-stratigraphic units within flood deposits. We have analyzed about 280 samples derived from 15 boreholes penetrating the giant Cold Creek flood bar. Paleomagnetic samples, obtained from finer-grained facies consisted of silt to coarse-grained sand. Demagnetization experiments consisted of alternating field or thermal demagnetization or a combination of both. Demagnetization revealed both reversed and normal polarities, although a substantial number of samples were of indeterminate polarity. The magnetostratigraphy suggests that these sediments have been accumulating since the Olduvai (1.77-1.95 Ma) normal subchron. This extends the chronology of cataclysmic flooding in Southeastern Washington back by more than a million years over previous studies.

  15. 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

  16. Tumor Types: Understanding Brain Tumors

    MedlinePlus

    ... Resources Tools & Publications Tumor Types: Understanding Brain Tumors World Health Organization (WHO) Updates Official Classification of Tumors ... Central Nervous System On May 9, 2016, the World Health Organization (WHO) published an official reclassification of ...

  17. 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

  18. 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

  19. [Outcome of relaying anterolateral thigh perforator flap in resurfacing the donor site wound following free anteromedial thigh perforator flap transfer for reconstruction of defect after oral tumor radical resection].

    PubMed

    Song, D J; Li, Z; Zhou, X; Zhang, Y X; Peng, X W; Zhou, B; Lyu, C L; Yang, L C; Peng, W

    2017-02-20

    Objective: To observe the outcome of relaying anterolateral thigh (ALT) perforator flap in resurfacing the donor site wound following free anteromedial thigh (AMT) perforator flap transfer for reconstruction of defect after oral tumor radical resection. Methods: From January 2013 to January 2016, 28 patients with oral tumor underwent radical resection in our hospital, leaving defects with size ranged from 6.5 cm×3.5 cm to 11.0 cm×7.5 cm which were reconstructed by free AMT perforator flaps with size ranged from 7.0 cm×4.0 cm to 12.0 cm×8.0 cm. All the arteries of AMT perforators were anastomosed with superior thyroid arteries, while the venae comitants were anastomosed with superior thyroid venae or internal jugular venae. The donor site wounds of free AMT perforator flaps were reconstructed by relaying ALT perforator flaps with size ranged from 8.0 cm×3.5 cm to 14.0 cm×7.5 cm. The relaying ALT perforator flap and wound edge were closed directly with layer interrupted suture. Postoperatively, the patients stayed in bed and received diet through nasal feeding tube, and the ordinary diet and lower extremity exercise were carried out from one week after operation. Results: The AMT and ALT perforators existed consistently in all patients. In 16 patients the venae comitants of AMT perforator arteries were anastomosed with superior thyroid venae in end-to-end fashion, while in 12 patients with internal jugular venae in end-to-side fashion. All flaps survived uneventfully about 2 weeks after operation, and the wounds healed smoothly. All patients were followed up for 6 to 30 months after operation. The sites repaired with free AMT perforator flaps were not bulky in appearance, with two-point discrimination distances ranged from 8 to 15 mm. The movement of tongue was not obviously affected, and patients could speak and eat normally. The texture and color of the sites repaired with relaying ALT perforator flaps were close to those of the adjacent tissue, and the two

  20. γ-secretase binding sites in aged and Alzheimer's disease human cerebrum: the choroid plexus as a putative origin of CSF Aβ.

    PubMed

    Liu, Fei; Xue, Zhi-Qin; Deng, Si-Hao; Kun, Xiong; Luo, Xue-Gang; Patrylo, Peter R; Rose, Gregory M; Cai, Huaibin; Struble, Robert G; Cai, Yan; Yan, Xiao-Xin

    2013-05-01

    Deposition of β -amyloid (Aβ) peptides, cleavage products of β-amyloid precursor protein (APP) by β-secretase-1 (BACE1) and γ-secretase, is a neuropathological hallmark of Alzheimer's disease (AD). γ-Secretase inhibition is a therapeutical anti-Aβ approach, although changes in the enzyme's activity in AD brain are unclear. Cerebrospinal fluid (CSF) Aβ peptides are thought to derive from brain parenchyma and thus may serve as biomarkers for assessing cerebral amyloidosis and anti-Aβ efficacy. The present study compared active γ-secretase binding sites with Aβ deposition in aged and AD human cerebrum, and explored the possibility of Aβ production and secretion by the choroid plexus (CP). The specific binding density of [(3) H]-L-685,458, a radiolabeled high-affinity γ-secretase inhibitor, in the temporal neocortex and hippocampal formation was similar for AD and control cases with similar ages and post-mortem delays. The CP in post-mortem samples exhibited exceptionally high [(3) H]-L-685,458 binding density, with the estimated maximal binding sites (Bmax) reduced in the AD relative to control groups. Surgically resected human CP exhibited APP, BACE1 and presenilin-1 immunoreactivity, and β-site APP cleavage enzymatic activity. In primary culture, human CP cells also expressed these amyloidogenic proteins and released Aβ40 and Aβ42 into the medium. Overall, our results suggest that γ-secretase activity appears unaltered in the cerebrum in AD and is not correlated with regional amyloid plaque pathology. The CP appears to be a previously unrecognised non-neuronal contributor to CSF Aβ, probably at reduced levels in AD.

  1. 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

  2. New 40Ar/39Ar age of the Bishop Tuff from multiple sites and sediment rate calibration for the Matuyama-Brunhes boundary

    USGS Publications Warehouse

    Sarna-Wojcicki, A. M.; Pringle, M.S.; Wijbrans, J.

    2000-01-01

    Precise dating of sanidine from proximal ash flow Bishop Tuff and air fall Bishop pumice and ash, California, can be used to derive an absolute age of the Matuyama Reversed-Brunhes Normal (M-B) paleomagnetic transition, identified stratigraphically close beneath the Bishop Tuff and ash at many sites in the western United States. An average age of 758.9 ?? 1.8 ka, standard error of the mean (SEM), was obtained for individual sanidine crystals or groups of several crystals, determined from ???70 individual analyses of sanidine separates from 11 sample groups obtained at five localities. The basal air fall pumice (757.7 ?? 1.8 ka) and overlying ash flow tuff (762.2 ?? 4.7 ka) from near the source yield essentially the same dates within errors of analysis, suggesting that the two units were emplaced close in time. A date on distal Bishop air fall ash bed at Friant, California, ???100 km to the west of the source area, is younger, 750.1 ?? 4.3 ka, but not significantly different within analytical error (??1 standard deviation). Previous dates of the Bishop Tuff, obtained by others using conventional K-Ar and the fission track method on zircons, ranged from ???650 ka to ???1.0 Ma. The most recent, generally accepted date by the K-Ar method on sanidine was 738 ?? 3 ka. We infer, as others before, that many K-Ar dates on sanidine feldspar are too young owing to incomplete degassing of radiogenic Ar during fusion in the K-Ar technique and that many older K-Ar dates are too old owing to detrital or xenocrystic contamination in the larger samples that are necessary for the technique. The new dates are similar to recent 40Ar/39Ar ages of the Bishop Tuff determined on individual samples by others but are derived from a larger proximal sample population and from multiple analysis of each sample. The results provide a definitive and precise age calibration of this widespread chronostratigraphic marker in the western United States and northeastern Pacific Ocean. We calculated the

  3. Investigation of the age trends in patients with breast cancer and different sizes of tumors in Breast Cancer Research Center of Isfahan University of Medical Sciences in 2001-2010

    PubMed Central

    Tazhibi, Mehdi; Dehkordi, Zahra Fazeli; Babazadeh, Shadi; Tabatabaeian, Maryam; Rezaei, Parisa; Faghihi, Mehri

    2014-01-01

    Background: Breast cancer is the most common cause of death in women in the age range of 35-55 years. Each year, one or two cases of breast cancer per 1000 women are diagnosed as new cases. Despite the serious prognosis and high rate of morbidity, mortality, and pathogenicity, in the case of early diagnoses, the prognosis will be better. The aim of this study was to investigate the age trends in breast cancer patients with different sizes of tumors in Breast Cancer Research Center of Isfahan University of Medical Sciences in 2001-2010. Materials and Methods: The information in radiotherapy and oncology of Isfahan University of Medical Sciences and Milad Hospital from 2001 to 2010 were coded and analyzed. Frequency of patients’ age groups, tumor sizes and the year of cancer diagnosis were calculated. Correlation test was used for data analysis in statistical analysis in social science (SPSS) software version 18. Findings: Among the 3722 patients with breast cancer, the highest relative frequency distribution, respectively was observed in the age of 40-49 years (34.4%), 50-59 years (26.6%), 30-39 years (17.7%), 60-69 years (13.2%), 20-29 years (2.5%), 70 years and older (5.2%) and less than 20 years. Relative frequency distribution of tumor sizes in a variety of 5 cm (T2) was with the frequency of 59.8%, and then 26% at 5 cm (T3), 10.5% at 2 cm (T1), 3.1% at T4 and 0.6 at In-situ, respectively. Conclusion: The investigation of age trends showed that diagnosis rate of breast cancer increased from 2001 to 2004. It reached its highest value in 2006 at the age range of 30-39 years. Then, the trend has been downward, and it has continued to decline until 2010, which could be the result of the equipping screening system and recording the malignant cases. 85.8% of the examined tumors in T2 and T3 group were visible and may be disturbing. Comparing the frequency distribution of the infected population showed that the highest incidence of breast cancer diagnosis were in the

  4. Tumor development following internal exposures to radionuclides during the perinatal period

    SciTech Connect

    Sikov, M.R.

    1988-07-01

    Exposure to radiation from internally deposited radionuclides during the prenatal and/or neonatal periods involves a distinct oncogenic potential. The fundamental mechanisms for perinatal radionuclide carcinogenesis seem to be generally similar to those that pertain to external radiation exposures and other carcinogenic agents, but unique interactions may be superimposed. Specific dose-effect relationships differ among radionuclides; many studies find dose-related increases in the incidence of tumors or decreases in age at tumor appearance following prenatal or neonatal radiation exposures. Tumor incidences may be decreased, especially at high dose levels; these are usually attributable to cell death, inhibited development of target tissues, or to endocrine malfunction. Age-related differences in predominant tumor types and/or sites of tumor development are often detected, and are explainable by the existence of nuclide-specific target organs or tissues, dosimetric factors, and developmental considerations. 34 refs.

  5. Correlation of the KHS Tuff of the Kibish Formation to volcanic ash layers at other sites, and the age of early Homo sapiens (Omo I and Omo II).

    PubMed

    Brown, Francis H; McDougall, Ian; Fleagle, John G

    2012-10-01

    Hominin specimens Omo I and Omo II from Member I of the Kibish Formation, Ethiopia are attributed to early Homo sapiens, and an age near 196 ka has been suggested for them. The KHS Tuff, within Member II of the Kibish Formation has not been directly dated at the site, but it is believed to have been deposited at or near the time of formation of sapropel S6 in the Mediterranean Sea. Electron microprobe analyses suggest that the KHS Tuff correlates with the WAVT (Waidedo Vitric Tuff) at Herto, Gona, and Konso (sample TA-55), and with Unit D at Kulkuletti in the Ethiopian Rift Valley. Konso sample TA-55 is older than 154 ka, and Unit D at Kulkuletti is dated at 183 ka. These correlations and ages provide strong support for the age originally suggested for the hominin remains Omo I and Omo II, and for correlation of times of deposition in the Kibish region with formation of sapropels in the Mediterranean Sea. The Aliyo Tuff in Member III of the Kibish Formation is dated at 104 ka, and correlates with Gademotta Unit 15 in the Ethiopian Rift Valley.

  6. 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

  7. Completeness of required site-specific factors for brain and CNS tumors in the Surveillance, Epidemiology and End Results (SEER) 18 database (2004-2012, varying).

    PubMed

    Ostrom, Quinn T; Gittleman, Haley; Kruchko, Carol; Louis, David N; Brat, Daniel J; Gilbert, Mark R; Petkov, Valentina I; Barnholtz-Sloan, Jill S

    2016-10-01

    Cancer registries are an important source of population-level information on brain tumor incidence and survival. Surveillance, Epidemiology, and End Results (SEER) registries currently collect data on specific required factors related to brain tumors as defined by the American Joint Commission on Cancer, including World Health Organization (WHO) grade, MGMT methylation and 1p/19q codeletion status. We assessed 'completeness', defined as having valid values over the time periods that they have been collected, overall, by year, histology, and registry. Data were obtained through a SEER custom data request for four factors related to brain tumors for the years 2004-2012 (3/4 factors were collected only from 2010 to 2012). SEER*Stat was used to generate frequencies of 'completeness' for each factor overall, and by year, histology and registry. The four factors varied in completeness, but increased over time. WHO grade has been collected the longest, and showed significant increases in completeness. Completeness of MGMT and 1p/19q codeletion was highest for glioma subtypes for which testing is recommended by clinical practice guidelines. Completeness of all factors varied by histology and cancer registry. Overall, several of the factors had high completeness, and all increased in completeness over time. With increasing focus on 'precision medicine' and the incorporation of molecular parameters into the 2016 WHO CNS tumor classification, it is critical that the data are complete, and factors collected at the population level are fully integrated into cancer reporting. It is critical that cancer registries continue to collect established and emerging prognostic and predictive factors.

  8. Spine cryoablation: A multimodality image-guided approach for tumors adjacent to major neural elements

    PubMed Central

    Guenette, Jeffrey P.; Tuncali, Kemal; Himes, Nathan; Tatli, Servet; Lee, Thomas C.

    2016-01-01

    We report percutaneous cryoablation of spine tumors in 7 consecutive patients (5 males, 2 females; mean age 47 years, range 17-68) using intraprocedural image monitoring of ice ball margins to protect adjacent neural elements. Complete tumor ablation was achieved in all patients without neurological complication. Pain relief was achieved in 4 of 5 (80%) patients; the patient with persistent pain was later found to have enlarging metastases at other sites. PMID:27609619

  9. CT-guided percutaneous microwave ablation of pulmonary malignant tumors

    PubMed Central

    Ko, Wei-Chun; Lee, Yee-Fan; Chen, Yi-Chang; Chien, Ning; Huang, Yu-Sen; Tseng, Yao-Hui; Lee, Jang-Ming; Hsu, Hsao-Hsun; Chen, Jin-Shing

    2016-01-01

    Background Microwave ablation (MWA) of lung tumors is a new approach for local tumor control. The purpose of this retrospective study was to evaluate the preliminary results of safety and efficacy of MWA with a dynamic frequency range (902–928 MHz) and power (10–32 W) for local tumor control of thoracic malignancies. Methods From December 1, 2013 to February 1, 2016, there were total 32 lung tumors among 15 patients (7 men, 8 women, age range 43–82 years, mean 57.8±11.1 years of age) receiving MWA of thoracic neoplasms, including lung adenocarcinoma (n=5), metastatic colorectal cancer (n=7), invasive thymoma (n=1), metastatic uterine leiomyosarcoma (n=1), and metastatic ampullary carcinoma (n=1). Mean tumor size was 13.5 mm (range, 3.0–32.0 mm). The mean sequential ablation during each MWA was 2.3±1.1 times (range, 1–5 times). The outcomes of ablation were evaluated by follow-up computed tomography (CT) scans and the complications were assessed by medical records and CT scan after ablation. Results The mean follow-up interval of each tumor was 446.8 days (range, 196–902 days). Local tumor recurrence was found in 5 of the 32 tumors resulting in a local control rate 84.4%. No MWA-related mortality was noted. After MWA, the incidence of pneumothorax was 37.5% (12/32). Only one patient with pneumothorax required air evacuation. Third-degree skin burn adjacent to the entry site occurred in one patient and required debridement and closure with flap. Conclusions After appropriate patient selection, MWA with a dynamic frequency range (902–928 MHz) and power (10–32 W) is an effective and safe procedure for local tumor control of recurrent and metastatic lung tumors. PMID:28066666

  10. The clinical characteristics of benign oral mucosal tumors

    PubMed Central

    Kaplan, Ilana; Gal, Gavriel; Chaushu, Gavriel; Allon, Dror M.

    2014-01-01

    Objectives: To investigate the clinical characteristics and pre-biopsy provisional diagnoses of benign oral mucosal tumors. Material and Methods: A 10- year retrospective analysis of all benign tumors of the oral mucosa, from a university- affiliated oral and maxillofacial surgery department. Results: 146 benign tumors were included. The mean age was 49.6 years, with an approximately equal gender distribution. The most prevalent tumor types were lipomatous tumors (27.4%), vascular (23.3%), and salivary gland tumors (16.5%). Tongue, labial and buccal mucosa were the most frequently involved sites. The vast majority (98.6%) presented as non-ulcerated masses. Only 2 (1.4%) presented as ulcerated masses. The clinical provisional diagnosis correctly classified lesions as non-malignant in 93.3%. In only 9 (6.7%) suspicion of malignancy was included in the provisional diagnosis. However, benign neoplasia was unsuspected in 42.1% of tumors. These cases were clinically classified as reactive. Conclusions: Benign tumors were most likely to be clinically correctly classified as non-malignant, but even in the setting of experienced oral surgeons, neoplasia was unsuspected in more than 40% of cases. This data strongly supports the need to biopsy every oral mucosal mass, since inaccurate clinical evaluation of the lesion’s biological nature was a frequent event. Key words:Malignant, benign, reactive, ulcerated mass, non-ulcerated mass, clinical diagnosis. PMID:24316705

  11. Extrauterine epithelioid trophoblastic tumor in hysterectomized woman

    PubMed Central

    Kim, Ji-Hye; Lee, Sun Kyung; Hwang, Soo Hyun; Kim, Jung-Sun; Yoon, Gun; Lee, Yoo-Young; Kim, Tae-Joong; Choi, Chel Hun; Kim, Byoung-Gie; Bae, Duk-Soo

    2017-01-01

    Epithelioid trophoblastic tumor (ETT) is a very rare variant of gestational trophoblastic disease (GTD) which arises in reproductive age women with prior gestational history. Although abnormal vaginal bleeding is the most common symptom of ETT, there are no reported pathognomonic symptoms of ETT because of its rarity. ETT is similar to placental site trophoblastic tumor in terms of its slow growing characteristic and microscopic findings. Therefore, it could be misdiagnosed as placental site trophoblastic tumor or other types of GTD. Unlike other types of GTD, primary treatment of ETT is surgical resection because of its chemo-resistant nature. Accordingly, immunohistochemical staining is essential for accurate diagnosis and appropriate treatment. Here, we report a case of a 42-year-old hysterectomized woman with pelvic masses who suffered from abdominal pain. Through laparotomy, tumors were resected completely and they were diagnosed as ETT through immunohistochemical stain. This report provides more evidence about its clinical features, diagnosis, and treatment including a brief review of the literature. PMID:28217684

  12. Age- and size-specific patterns of heavy metals in the organs of freshwater fish Abramis brama L. populating a low-contaminated site.

    PubMed

    Farkas, Anna; Salánki, János; Specziár, András

    2003-03-01

    Concentrations of cadmium, copper, mercury, lead and zinc were determined by atomic absorption spectrophotometry in the muscle, gill and liver of bream Abramis brama L. to study the relationship between the heavy metal load of fish and their age and size, and the seasonal variation of pollutant loads. Fish were collected from the Western basin of Lake Balaton (Hungary) in October 1999 and May 2000. The average metal concentrations of different organs varied in the following ranges: Cd 0.42-2.10; Cu 1.77-56.2; Hg 0.01-0.19; Pb 0.44-3.24; Zn 10.9-82.5 microg g(-1) dry weight. The highest Cd, Cu, Pb and Zn concentrations were detected in the gill or liver of fish, whereas the highest Hg concentrations were measured in the muscle. In the liver of bream for cadmium, copper and mercury the Pearson correlation analysis revealed positive associations related to age and size (length, net weight), as well as for the mercury load of all three investigated organs. In the muscle and gill the copper, lead and zinc concentrations, similarly to the lead and zinc concentrations of the liver, the associations related to age and size were negative. The correlations between the heavy metal concentrations of organs and the individual condition factors of fish samples proved to have opposite trends compared to those related to the age and size of fish. The seasonal variations in the heavy metal load of bream could be attributed rather to the seasonal change in the condition factor of fish than to variations in the pollutant load of the site.

  13. Propofol and remifentanil effect-site concentrations estimated by pharmacokinetic simulation and bispectral index monitoring during craniotomy with intraoperative awakening for brain tumor resection.

    PubMed

    Lobo, Francisco; Beiras, Aldara

    2007-07-01

    Different anesthetic techniques have been suggested for craniotomy with intraoperative awakening. We describe an asleep-awake-asleep technique with propofol and remifentanil infusions, with pharmacokinetic simulation to predict the effect-site concentrations and to modulate the infusion rates of both drugs, and bispectral index (BIS) monitoring. Five critical moments were defined: first loss of consciousness (LOC1), first recovery of consciousness (ROC1), final of neurologic testing (NT), second loss of consciousness (LOC2), and second recovery of consciousness (ROC2). At LOC1, predicted effect-site concentrations of propofol and remifentanil were, respectively, 3.6+/-1.2 microg/mL and 2.4+/-0.4 etag/mL. At ROC1, predicted effect-site concentrations of propofol and remifentanil were, respectively, 2.1+/-0.3 microg/mL and 1.8+/-0.3 etag/mL. At NT, predicted effect-site concentrations of propofol and remifentanil were, respectively, 0.9+/-0.3 microg/mL and 1.8+/-0.2 etag/mL. At LOC2, predicted effect-site concentrations of propofol and remifentanil were, respectively, 2.1+/-0.2 microg/mL and 2.5+/-0.2 etag/mL. At ROC2, predicted effect-site concentrations of propofol and remifentanil were, respectively, 1.2+/-0.5 microg/mL and 1.4+/-0.2 etag/mL (data are mean+/-SE). A significative correlation was found between BIS and predicted effect-site concentrations of propofol (r=0.547, P<0.001) and remifentanil (r=0.533, P<0.001). Multiple regression analysis between BIS and propofol and remifentanil predicted effect-site concentrations at the different critical steps of the procedure was done and found also significative (r=0.7341, P<0.001).

  14. Long-term all-sites cancer mortality time trends in Ohio, USA, 1970–2001: differences by race, gender and age

    PubMed Central

    Tyczynski, Jerzy E; Berkel, Hans J

    2005-01-01

    Background There were significant changes in cancer mortality in the USA over the last several decades, in the whole country and in particular states. However, no in depth analysis has been published so far, dealing with changes in mortality time trends in the state of Ohio. Since the state of Ohio belongs to the states of relatively high level of all-sites mortality in both males and females, it is of interest to analyze recent changes in mortality rates, as well as to compare them with the situation in the rest of the USA. The main aim of this study was to analyze, describe and interpret all-sites cancer mortality time trends in the population of the State of Ohio. Methods Cancer mortality data by age, sex, race and year for the period 1970–2001 were obtained from the Surveillance Research Program of the National Cancer Institute SEER*Stat software. A joinpoint regression methodology was used to provide estimated annual percentage changes (EAPCs) and to detect points in time where significant changes in the trends occurred. Results In both, males and females mortality rates were higher in blacks compared with whites. The difference was bigger in males (39.9%) than in women (23.3%). Mortality rates in Ohio are generally higher than average USA rates – an overall difference was 7.5% in men in 1997–2001, and 6.1% in women. All-sites mortality trends in Ohio and in the whole USA are similar. However, in general, mortality rates in Ohio remained elevated compared with the USA rates throughout the entire analyzed period. The exceptions are the rates in young and middle-aged African Americans. Conclusion Although direction of time trends in Ohio are similar in Ohio and the whole US, Ohio still have cancer mortality rates higher than the US average. In addition, there is a significant discrepancy between white and black population of Ohio in all-sites mortality level, with disadvantage for Blacks. To diminish disparities in cancer mortality between African

  15. 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

  16. 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.

  17. [Aging and gynecologic cancer].

    PubMed

    Arrighi, Arturo A

    2005-01-01

    The interrelation between cancer and ageing in women is emphasized, on its increased incidence, in their molecular background, into the particular biological characteristics of the different tumors and the effects of ageing in the affected women.

  18. 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

  19. 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

  20. Tracheal and bronchial tumors

    PubMed Central

    Pio, Luca; Brandigi, Elisa; Paraboschi, Irene; Khen-Dunlop, Nazhia; Hervieux, Erik; Muller, Cecile; Mattioli, Girolamo; Sarnacki, Sabine; Torre, Michele

    2016-01-01

    Although primary tracheobronchial tumors are extremely rare in children, recurrent respiratory symptoms resistant to conventional therapy require further investigations to exclude possible malignant obstructive causes. As the matter of fact, early diagnosis may allow minimally invasive surgeries, improving the standard of living and the globally survival rate. The aim of this article is to provide an overview of diagnosis and management of tracheobronchial tumors in the early age, since only few reports are reported in the worldwide literature. PMID:28149577

  1. Small mammal utilization by Middle Stone Age humans at Die Kelders Cave 1 and Pinnacle Point Site 5-6, Western Cape Province, South Africa.

    PubMed

    Armstrong, Aaron

    2016-12-01

    Reported here are the results of a taphonomic analysis of the small mammals (between 0.75 kg and 4.5 kg adult body weight) and size 1 bovids (≤20 kg adult body weight) from the Middle Stone Age (MSA) sites of Die Kelders Cave 1 (DK1) and Pinnacle Point Site 5-6 (PP5-6), Western Cape Province, South Africa. This study provides a comprehensive taphonomic analysis of MSA small mammals with a focus on discerning the role of humans in their accumulation and the implications for human behavioral adaptations. Based on comparisons with control assemblages of known accumulation, it is evident that humans accumulated many of the Cape dune mole-rats, hares, and size 1 bovids at DK1. The patterning of cut-marked and burned mole-rat remains at DK1 provides evidence in the MSA for the systematic utilization of small mammals for their skins and as a protein source. Unlike DK1, small mammals and size 1 bovids constitute only a small portion of the PP5-6 mammals and they exhibit little evidence of human accumulation. Nocturnal and diurnal raptors accumulated most of the small fauna at PP5-6. The nominal presence of small mammals in the PP5-6 fauna is atypical of MSA sites in the Cape Floristic Region, where they are abundant and often constitute large portions of MSA archaeofaunas. DK1 humans maximized the environmental yield by exploiting low-quality resources, a strategy employed possibly in response to localized environmental conditions and to greater human population densities. In comparison, the MIS5-4 humans at PP5-6 did not exploit small mammals and instead focused on higher-quality resources like shellfish and large ungulates. Humans and predators accumulated few small mammals at PP5-6, suggesting that these taxa may have been less abundant near the site and/or that humans could afford to concentrate on high-quality resources, perhaps because of a higher-yield local environment. This study suggests that an adaptive response to the environmental conditions of MIS4 was

  2. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor.

    PubMed Central

    Mink, S; Härtig, E; Jennewein, P; Doppler, W; Cato, A C

    1992-01-01

    Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. Images PMID:1328867

  3. Myeloid Cells in the Tumor Microenvironment: Modulation of Tumor Angiogenesis and Tumor Inflammation

    PubMed Central

    Schmid, Michael C.; Varner, Judith A.

    2010-01-01

    Myeloid cells are a heterogeneous population of bone marrow-derived cells that play a critical role during growth and metastasis of malignant tumors. Tumors exhibit significant myeloid cell infiltrates, which are actively recruited to the tumor microenvironment. Myeloid cells promote tumor growth by stimulating tumor angiogenesis, suppressing tumor immunity, and promoting metastasis to distinct sites. In this review, we discuss the role of myeloid cells in promoting tumor angiogenesis. Furthermore, we describe a subset of myeloid cells with immunosuppressive activity (known as myeloid-derived suppressor cells). Finally, we will comment on the mechanisms regulating myeloid cell recruitment to the tumor microenvironment and on the potential of myeloid cells as new targets for cancer therapy. PMID:20490273

  4. A series of collision tumors in the genitourinary tract with a review of the literature.

    PubMed

    Anani, Waseem; Amin, Milon; Pantanowitz, Liron; Parwani, Anil V

    2014-04-01

    Collision tumors, characterized by the coexistence of phenotypically and genotypically distinct tumors at the same site, are distinctly rare in the genitourinary tract and pose a diagnostic challenge. The goal of this study is to present a series of such cases from a single institution highlighting the unusual clinicopathologic features of these tumors. Six cases were retrospectively identified from our surgical pathology files and included internal and consultation cases (2006-2012). All tumors were identified by H&E and selected immunohistochemistry. There were 5 males and 1 female patients ranging in age from 57 to 84 years (average 73 years). The sites of these collision tumors were located in the kidney (3 cases), bladder (2 cases), and prostate. All collision tumors involved at least one malignant neoplasm. The diagnosis of collision tumors in the genitourinary tract is a perplexing task. Awareness of these rare entities, thorough sampling of the tumor mass, and appropriate use of ancillary techniques to demonstrate the different tumor components can help avoid an incorrect diagnosis, as well as with pathologic staging.

  5. Ten-year incident osteoporosis-related fractures in the population-based Canadian Multicentre Osteoporosis Study — Comparing site and age-specific risks in women and men

    PubMed Central

    Prior, Jerilynn C.; Langsetmo, Lisa; Lentle, Brian C.; Berger, Claudie; Goltzman, David; Kovacs, Christopher S.; Kaiser, Stephanie M.; Adachi, Jonathan D.; Papaioannou, Alexandra; Anastassiades, Tassos; Towheed, Tanveer; Josse, Robert G.; Brown, Jacques P.; Leslie, William D.; Kreiger, Nancy

    2016-01-01

    Background Population-based incident fracture data aid fracture prevention and therapy decisions. Our purpose was to describe 10-year site-specific cumulative fracture incidence by sex, age at baseline, and degree of trauma with/without consideration of competing mortality in the Canadian Multicentre Osteoporosis Study adult cohort. Methods Incident fractures and mortality were identified by annual postal questionnaires to the participant or proxy respondent. Date, site and circumstance of fracture were gathered from structured interviews and medical records. Fracture analyses were stratified by sex and age at baseline and used both Kaplan–Meier and competing mortality methods. Results The baseline (1995–97) cohort included 6314 women and 2789 men (aged 25–84 years; mean ± SD 62 ± 12 and 59 ± 14, respectively), with 4322 (68%) women and 1732 (62%) men followed to year-10. At least one incident fracture occurred for 930 women (14%) and 247 men (9%). Competing mortality exceeded fracture risk for men aged 65+ years at baseline. Age was a strong predictor of incident fractures especially fragility fractures, with higher age gradients for women vs. men. Major osteoporotic fracture (MOF) (hip, clinical spine, forearm, humerus) accounted for 41–74% of fracture risk by sex/age strata; in women all MOF sites showed age-related increases but in men only hip was clearly age-related. The most common fractures were the forearm for women and the ribs for men. Hip fracture incidence was the highest for the 75–84 year baseline age-group with no significant difference between women 7.0% (95% CI 5.3, 8.9) and men 7.0% (95% CI 4.4, 10.3). Interpretation There are sex differences in the predominant sites and age-gradients of fracture. In older men, competing mortality exceeds cumulative fracture risk. PMID:25451323

  6. 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

  7. 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 ...

  8. 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.

  9. Wilms Tumor

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Wilms Tumor KidsHealth > For Parents > Wilms Tumor Print A A A What's in this article? ... their child has cancer. Fortunately, most kids with Wilms tumor, a rare kidney cancer, survive and go on ...

  10. Alpha1-antitrypsin inhibits angiogenesis and tumor growth.

    PubMed

    Huang, Hanhua; Campbell, Steven C; Nelius, Thomas; Bedford, Dhugal F; Veliceasa, Dorina; Bouck, Noel P; Volpert, Olga V

    2004-12-20

    Disturbances of the ratio between angiogenic inducers and inhibitors in tumor microenvironment are the driving force behind angiogenic switch critical for tumor progression. Angiogenic inhibitors may vary depending on organismal age and the tissue of origin. We showed that alpha(1)-antitrypsin (AAT), a serine protease inhibitor (serpin) is an inhibitor of angiogenesis, which induced apoptosis and inhibited chemotaxis of endothelial cells. S- and Z-type mutations that cause abnormal folding and defective serpin activity abrogated AAT antiangiogenic activity. Removal of the C-terminal reactive site loop had no effect on its angiostatic activity. Both native AAT and AAT truncated on C-terminus (AATDelta) inhibited neovascularization in the rat cornea and delayed the growth of subcutaneous tumors in mice. Treatment with native AAT and truncated AATDelta, but not control vehicle reduced tumor microvessel density, while increasing apoptosis within tumor endothelium. Comparative analysis of the human tumors and normal tissues of origin showed correlation between reduced local alpha(1)-antitrypsin expression and more aggressive tumor growth.

  11. 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.

  12. 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

  13. Prospective Study of 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography for Detecting Gastro-Entero-Pancreatic Neuroendocrine Tumors and Unknown Primary Sites

    PubMed Central

    Sadowski, Samira M.; Neychev, Vladimir; Millo, Corina; Shih, Joanna; Nilubol, Naris; Herscovitch, Peter; Pacak, Karel; Marx, Stephen J.

    2016-01-01

    Purpose Gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) are increasing in incidence, and accurate staging is important for selecting the appropriate treatment. 68Ga-DOTATATE imaging is a promising approach for detecting GEPNETs and could help in selecting optimal therapeutic strategies. The aim of this study was to prospectively determine the clinical utility of 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) in detecting unknown primary and metastatic GEPNETs. Patients and Methods One hundred thirty-one patients were enrolled in a prospective study of patients undergoing 68Ga-DOTATATE PET/CT, 111In-pentetreotide single-photon emission computed tomography (SPECT)/CT and multiphasic CT scan, and/or magnetic resonance imaging in a blinded fashion with comprehensive biochemical testing. The primary outcome measure was the detection of lesions by each imaging study. Results 68Ga-DOTATATE PET/CT imaging detected 95.1% of lesions (95% CI, 92.4% to 96.8%) with an average maximum standardized uptake value of 65.4 ± 47 (range, 6.9 to 244), anatomic imaging detected 45.3% of lesions (95% CI, 37.9% to 52.9%), and 111In-pentetreotide SPECT/CT detected 30.9% of lesions (95% CI, 25.0% to 37.5%), with a significant difference between imaging modalities (P < .001). In four of 14 patients (28.6%), 68Ga-DOTATATE PET/CT found a previously unknown primary tumor, and detected primary GEPNET, lymph node, and distant metastases correctly in 72 of 113 lesions (63.7%) when compared with histopathology, with 22.1% and 38.9% detected by using 111In-pentetreotide SPECT/CT and anatomic imaging, respectively. On the basis of findings with 68Ga-DOTATATE PET/CT, 43 of 131 patients (32.8%) had a change in management recommendation. In patients with carcinoid symptoms but negative biochemical testing, 68Ga-DOTATATE PET/CT detected lesions in 65.2% of patients, 40% of which were detected neither by anatomic imaging nor by 111In-pentetreotide SPECT/CT. Conclusion

  14. Epididymal Adenomatoid Tumor: A Very Rare Paratesticular Tumor of Childhood

    PubMed Central

    Kaselas, Christos; Theocharides, Constantine; Kalogirou, Maria; Farmakis, Konstantinos; Feidantsis, Thomas

    2016-01-01

    Adenomatoid tumor is an uncommon benign mesothelial neoplasm, usually localized in the epididymis. It is the most common paratesticular tumor of middle-aged patients (average age of clinical presentation: 36 years). However, these tumors in pediatric and pubertal patients are extremely rare. Due to their rarity, we present a case of adenomatoid tumor of the tail of the epididymis in a 16-year-old patient. After systematic research of the current literature, we did not find another case report of epididymal adenomatoid tumor in a male patient aged 16 years old or less. This notice and our concern, as well, about the patient's surveillance protocol during the postoperative period were the motive for this case study. PMID:28003830

  15. Tracheobronchial tumors

    PubMed Central

    Milenkovic, Branislava

    2016-01-01

    Tumors of trachea and bronchi are uncommon and can occur in the form of benign or low- and high-grade malignant tumors. Although tracheobronchial tumors (TBTs) represent only 0.6% of all pulmonary tumors, they are clinically significant. Delays in diagnosis of these tumors commonly occur because the signs and symptoms caused by these tumors are nonspecific and chest radiographs are often considered unremarkable. Therefore, novel radiological techniques and better access to flexible bronchoscopy enable detection of larger number of TBT. The purpose of this article is to provide a review of tracheal and bronchial tumors and discuss significant aspects of the different TBT with focus on clinical manifestations and diagnostic procedures. PMID:28066620

  16. Radiology of juxtaglomerular tumors

    SciTech Connect

    Dunnick, N.R.; Hartman, D.S.; Ford, K.K.; Davis, C.J. Jr.; Amis, E.S. Jr.

    1983-05-01

    Nine cases of proven juxtaglomerular tumor of the kidney are reviewed. Each patient presented with hypertension; elevated peripheral renin levels were found in four patients. As in past studies, this tumor occurred more frequently in women (7/9 cases). Although the patients tended to be younger (mean age, 31 years) than those with essential hypertension, all but two patients were more than 20 years of age. In all cases, the tumor was solitary, well-defined, and curable by surgery. The tumor was identified by excretory urography in 5/8 patients who underwent this procedure. A solid renal mass was detected in each of the seven patients examined by ultrasound. Since the tumor tends to be isodense with normal renal parenchyma, it is sometimes not seen on computed tomography without intravenouse contrast material. Arteriography revealed a hypovascular mass in each of the nine patients. The combination of a hypovascular solid renal mass in a patient with elevated renin but no renal artery lesions should suggest the diagnosis of a juxtaglomerular cell tumor.

  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. 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.

  19. A multicenter study of oral malignant tumors from Thailand

    PubMed Central

    Dhanuthai, Kittipong; Rojanawatsirivej, Somsri; Subarnbhesaj, Ajiravudh; Thosaporn, Watcharaporn; Kintarak, Sompid

    2016-01-01

    Background: Oral malignant tumors in Thailand have not been extensively studied. Hence the following study was conducted. Aims: To determine the prevalence and clinicopathologic data of the oral malignant tumors from Thailand. Subjects and Methods: Biopsy records of the Oral Pathology Department, Chulalongkorn University; Department of Oral Biology and Diagnostic Sciences, Chiang Mai University; Department of Oral Diagnosis, Khon Kaen University and Department of Stomatology, Prince of Songkla University, were reviewed for lesions diagnosed in the category of oral malignant tumors from 2005–2014. Demographic data and site of the lesions were collected. Statistical Analysis Used: Data were analyzed by descriptive statistics using SPSS software version 17.0. Results: Of the 22,639 accessioned cases, 1411 cases (6.23%) were diagnosed as oral malignant tumors. The mean age of the patients was 59.13 ± 17.32 years. A total of 651 cases (46.14%) were diagnosed in males, whereas 759 cases (53.79%) were diagnosed in females. The male-to-female ratio was 0.86:1. The sites of predilection for oral malignant tumors were the gingiva, followed by tongue and alveolar mucosa. The three most common oral malignant tumors in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions: This study provides extensive data on the oral malignant tumors from several university biopsy services located in virtually all parts of Thailand. The data from the present study show some similarities with previous studies; however, differences such as gender and site of predilection still exist. PMID:27721612

  20. Sexy online self-presentation on social network sites and the willingness to engage in sexting: A comparison of gender and age.

    PubMed

    van Oosten, Johanna M F; Vandenbosch, Laura

    2017-01-01

    The present study investigated whether engaging in sexy self-presentations on social network sites (SNSs) or exposure to sexy self-presentations on SNSs predicts the willingness to engage in sexting. A second aim of the present study was to investigate whether adolescent girls demonstrate stronger relationships between (exposure to) sexy online self-presentations on SNSs and willingness to sext than adolescent boys and young adult men and women. A two-wave panel survey among 953 Dutch adolescents (13-17 years old, 50.7% male) and 899 Dutch young adults (18-25 years old, 43.9% male) showed that engaging in sexy self-presentations on SNSs increased the willingness to engage in sexting, but only among adolescent girls. Exposure to sexy self-presentations of others did not predict the willingness to engage in sexting. The findings call for more research on the role of gender and age in the link between sexy self-presentation and sexting.

  1. A Comprehensive Assessment by Tumor Site of Patient Setup Using Daily MVCT Imaging From More Than 3,800 Helical Tomotherapy Treatments

    SciTech Connect

    Schubert, Leah K. Westerly, David C.; Tome, Wolfgang A.; Mehta, Minesh P.; Soisson, Emilie T.; Mackie, Thomas R.; Ritter, Mark A.; Khuntia, Deepak; Harari, Paul M.; Paliwal, Bhudatt R.

    2009-03-15

    Purpose: To assess patient setup corrections based on daily megavoltage CT (MVCT) imaging for four anatomic treatment sites treated on tomotherapy. Method and Materials: Translational and rotational setup corrections, based on registration of daily MVCT to planning CT images, were analyzed for 1,179 brain and head and neck (H and N), 1,414 lung, and 1,274 prostate treatment fractions. Frequencies of three-dimensional vector lengths, overall distributions of setup corrections, and patient-specific distributions of random and systematic setup errors were analyzed. Results: Brain and H and N had lower magnitude positioning corrections and smaller variations in translational setup errors but were comparable in roll rotations. Three-dimensional vector translational shifts of larger magnitudes occurred more frequently for lung and prostate than for brain and H and N treatments, yet this was not observed for roll rotations. The global systematic error for prostate was 4.7 mm in the vertical direction, most likely due to couch sag caused by large couch extension distances. Variations in systematic errors and magnitudes of random translational errors ranged from 1.6 to 2.6 mm for brain and H and N and 3.2 to 7.2 mm for lung and prostate, whereas roll rotational errors ranged from 0.8{sup o} to 1.2{sup o} for brain and H and N and 0.5{sup o} to 1.0{sup o} for lung and prostate. Conclusions: Differences in setup were observed between brain, H and N, lung, and prostate treatments. Patient setup can be improved if daily imaging is performed. This analysis can assess the utilization of daily image guidance and allows for further investigation into improved anatomic site-specific and patient-specific treatments.

  2. A Comprehensive Assessment by Tumor Site of Patient Setup using Daily MVCT Imaging from Over Three Thousand Eight Hundred Helical Tomotherapy Treatments

    PubMed Central

    Schubert, Leah K.; Westerly, David C.; Tomé, Wolfgang A.; Mehta, Minesh P.; Soisson, Emilie T.; Mackie, Thomas R.; Ritter, Mark A.; Khuntia, Deepak; Harari, Paul M.; Paliwal, Bhudatt R.

    2009-01-01

    Purpose To assess patient setup corrections based on daily megavoltage CT (MVCT) imaging for four different anatomical treatment sites treated on tomotherapy. Method and Materials Translational and rotational per-fraction setup corrections, based on registration of daily helical MVCT to planning CT images, were analyzed for 1179 brain and head and neck (H&N), 1414 lung, and 1274 prostate tomotherapy treatment fractions. Frequencies of 3D vector lengths, overall distributions of setup corrections, and patient-specific distributions of random and systematic setup errors were analyzed. Results Brain and H&N had lower magnitude positioning corrections and smaller variations in setup errors in the translational directions, but were comparable in roll rotations. 3D vector translational shifts of larger magnitudes occurred more frequently for lung and prostate than for brain and H&N treatments, yet this was not observed for roll rotations. The global systematic error for prostate was 4.7 mm in the vertical direction, most likely due to couch sag caused by large couch extension distances. Patient-to-patient variations in systematic errors and magnitudes of random translational errors ranged from 1.6-2.6 mm for brain and H&N and 3.2-7.2 mm for lung and prostate while roll rotational errors ranged from 0.8-1.2° for brain and H&N and 0.5-1.0° for lung and prostate. Conclusions Differences in setup were observed between brain, H&N, lung, and prostate treatments. Patient setup can be improved if daily imaging is performed. This analysis can assess the utilization of daily image guidance and allows for further investigation into improved anatomical site-specific and patient-specific treatments. PMID:19251098

  3. Evaluation of the Olduvai Sub-Chron in the Orce Ravine (SE Spain), Implications for the Plio-Pleistocene Mammal Biostratigraphy and the Age of Orce Archaeological Sites

    NASA Astrophysics Data System (ADS)

    Gibert, L.; Scott, G. R.; Ferrandez, C.

    2002-12-01

    association from the BO section has been assigned to a total range of four biozones, MN17 to MmQ3. Another ambiguity exists in the previous magnetostratigraphic interpretation of the age of the BO section as early Matuyama (C2r.1r), in direct conflict with an assignment of late Matuyama (C1r.2r) in the nearby BL section. These adjacent sections can be stratigraphically correlated and are considered contemporaneous on geologic grounds. Our research shows that the Barranco de Orce section: [A] Crosses a mega-landslide, which produces repetition of parts of the sedimentary sequence, so that the seven fossiliferous layers (O-1 to O-7) are actually the repetition of only two (O-6 and O-7, 3m apart in situ in the upper part of the ravine). [B] New paleomagnetic results demonstrate the presence of reverse magnetization throughout this section. The BO magnetostratigraphy can now be directly correlated with the exclusively reverse polarity from the Barranco Leon section (published and new data) and with published reverse data from Fuentenueva-3. Therefore, all lithic artifact and paleontological sites in the Orce area are within a reverse magnetochron (presumably C1r.2r).

  4. The relative frequency of odontogenic tumors: A study of 376 cases in a Brazilian population

    PubMed Central

    Lima-Verde-Osterne, Rafael; Turatti, Eveline; Cordeiro-Teixeira, Renata

    2017-01-01

    Background Odontogenic tumors (OTs) are rare lesions, exclusive of the jaws, that are derived from epithelial and/or ectomesenchymal elements of the tooth-forming apparatus. Their biological behavior is heterogeneous, including hamartomatous tissue proliferation, benign nonaggressive and aggressive neoplasms, and malignant tumors with metastatic capacity. The aim of this study was to describe the relative frequency of odontogenic tumors in a Brazilian population. In addition, a review of the literature identified studies on odontogenic tumors that follow the 2005 World Health Organization. Material and Methods A total of 376 cases of odontogenic tumors from an oral pathology service were reviewed about age, gender, anatomic site and histologic diagnosis. Results Keratocystic odontogenic tumors (31.6%) were the most common, followed by ameloblastoma (28.5%), and odontoma (22.6%). The mean age was 32.2 years, and more than half the patients (52.1%) were in the second and third decades of life. The male to female ratio was 1:1.37, with a maxilla to mandible ratio of 1:2.08. Conclusions The variation in relative frequency of tumors observed among the several series, including the present study, is probably due in part to cultural differences between geographic areas but also to the study design. Key words:Pathology, epidemiology, odontogenic tumors. PMID:28160576

  5. Canine digital tumors: a veterinary cooperative oncology group retrospective study of 64 dogs.

    PubMed

    Henry, Carolyn J; Brewer, William G; Whitley, Elizabeth M; Tyler, Jeff W; Ogilvie, Gregory K; Norris, Alan; Fox, Leslie E; Morrison, Wallace B; Hammer, Alan; Vail, David M; Berg, John

    2005-01-01

    We compared clinical characteristics and outcomes for dogs with various digital tumors. Medical records and histology specimens of affected dogs from 9 veterinary institutions were reviewed. Risk factors examined included age, weight, sex, tumor site (hindlimb or forelimb), local tumor (T) stage, metastases, tumor type, and treatment modality. The Kaplan-Meier product limit method was used to determine the effect of postulated risk factors on local disease-free interval (LDFI), metastasis-free interval (MFI), and survival time (ST). Outcomes were thought to differ significantly between groups when P < or = .003. Sixty-four dogs were included. Squamous cell carcinoma (SCC) accounted for 33 (51.6%) of the tumors. Three dogs presented with or developed multiple digital SCC. Other diagnoses included malignant melanoma (MM) (n = 10; 15.6%), osteosarcoma (OSA) (n = 4; 6.3%), hemangiopericytoma (n = 3; 4.7%), benign soft tissue tumors (n = 5; 7.8%), and malignant soft tissue tumors (n = 9; 14%). Fourteen dogs with malignancies had black hair coats, including 5 of the 10 dogs with MM. Surgery was the most common treatment and, regardless of the procedure, had a positive impact on survival. None of the patient variables assessed, including age, sex, tumor type, site, and stage, had a significant impact on ST. Both LDFI and MFI were negatively affected by higher T stage, but not by type of malignancy. Although metastasis at diagnosis correlated with a shorter LDFI, it did not have a significant impact on ST. On the basis of these findings, early surgical intervention is advised for the treatment of dogs with digital tumors, regardless of tumor type or the presence of metastatic disease.

  6. 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 Central

    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-1α-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

  7. 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.

  8. 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.

  9. Carcinoid Tumors

    MedlinePlus

    Carcinoid tumors are rare, slow-growing cancers. They usually start in the lining of the digestive tract or in the lungs. They grow ... trouble breathing. Surgery is the main treatment for carcinoid tumors. If they haven't spread to other parts of the body, surgery can cure the cancer.

  10. Pituitary Tumors

    MedlinePlus

    ... pituitary is the "master control gland" - it makes hormones that affect growth and the functions of other glands in the body. Pituitary tumors are common, but often they don't cause health ... tumor produces hormones and disrupts the balance of hormones in your ...

  11. 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

  12. 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.

  13. Neuropsychological assessment at school-age and prenatal low-level exposure to mercury through fish consumption in an Italian birth cohort living near a contaminated site.

    PubMed

    Deroma, L; Parpinel, M; Tognin, V; Channoufi, L; Tratnik, J; Horvat, M; Valent, F; Barbone, F

    2013-07-01

    The relative effects of prenatal and postnatal low-level mercury exposure and fish intake on child neurodevelopment are still controversial. Limited evidence is available from Mediterranean populations. In this prospective study, we measured the Verbal and Performance IQ in Italian children at school-age who were resident in an area declared as a National contaminated site because of mercury pollution, taking into account the possible beneficial effect of fish consumption and potential confounders. A mother-child cohort made up of 242 children was established at birth in Northeastern Italy in 2001. Their mothers were interviewed approximately 2 months after delivery to determine type, quantity, and origin of fish consumed during pregnancy and about a number of mother, child and family characteristics. Total mercury (THg) and methyl mercury (MeHg) were assessed in maternal hair and breast milk and in the child's hair. When children reached 7-9 years of age, 154 (63.6%) parents gave consent to participate in a follow-up evaluation. On that occasion, a child's hair sample was collected to determine the current concentration of THg, mothers were asked to complete a self-administered questionnaire, and children underwent neuropsychological testing. Verbal IQ, performance IQ and full scale IQ were measured by the Wechsler Intelligence Scale for Children (WISC III) administered by psychologists at school or local health centers. Demographic, socioeconomic and lifestyle information, medical information of the child's family and the child's dietary habits were collected using a questionnaire filled in by mothers. Multivariable linear regression models were used to evaluate the association between prenatal THg exposure through fish consumption of mothers in pregnancy and children's IQ after adjustment for possible confounders such as fish consumption of mothers in pregnancy, child's fish consumption at follow-up, child's birthweight, maternal cigarette smoking during

  14. 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

  15. 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...

  16. Familiality in brain tumors

    PubMed Central

    Blumenthal, Deborah T.; Cannon-Albright, Lisa A.

    2008-01-01

    Background: Familiality in brain tumors is not definitively substantiated. Methods: We used the Utah Population Data Base (UPDB), a genealogy representing the Utah pioneers and their descendants, record-linked to statewide cancer records, to describe the familial nature of primary brain cancer. We examined the familial clustering of primary brain tumors, including subgroups defined by histologic type and age at diagnosis. The UPDB includes 1,401 primary brain tumor cases defined as astrocytoma or glioblastoma, all with at least three generations of genealogy data. We tested the hypothesis of excess relatedness of brain tumor cases using the Genealogical Index of Familiality method. We estimated relative risks for brain tumors in relatives using rates of brain tumors estimated internally. Results: Significant excess relatedness was observed for astrocytomas and glioblastomas considered as a group (n = 1,401), for astrocytomas considered separately (n = 744), but not for glioblastomas considered separately (n = 658). Significantly increased risks to first- and second-degree relatives for astrocytomas were identified for relatives of astrocytomas considered separately. Significantly increased risks to first-degree relatives, but not second degree, were observed for astrocytoma and glioblastoma cases considered together, and for glioblastoma cases considered separately. Conclusions: This study provides strong evidence for a familial contribution to primary brain cancer risk. There is evidence that this familial aspect includes not only shared environment, but also a heritable component. Extended high-risk brain tumor pedigrees identified in the UPDB may provide the opportunity to identify predisposition genes responsible for familial brain tumors. GLOSSARY GBM = glioblastoma; GIF = Genealogical Index of Familiality; HGG = high-grade gliomas; ICD-O = International Classification of Disease–Oncology; LGG = low-grade gliomas; RR = relative risks; SEER = Surveillance

  17. 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

  18. Magnetostratigraphy of sediments from Lake El'gygytgyn ICDP Site 5011-1: paleomagnetic age constraints for the longest paleoclimate record from the continental Arctic

    NASA Astrophysics Data System (ADS)

    Haltia, E. M.; Nowaczyk, N. R.

    2014-03-01

    Paleomagnetic measurements were performed on sediments drilled from ICDP Site 5011-1 in Lake El'gygytgyn (67°30' N, 172°05' E) located in Far East Russian Arctic. The lake partly fills a crater formed by a meteorite impact 3.58 ± 0.04 Ma ago. Sediments from three parallel cores (5011-1A, 5011-1B and 5011-1C), recovered from the middle part of the lake, yield a total of 355 m of sediment. Sediments are characterized by a variable lithology, where intervals of homogenous and laminated sediments alternate, and mass movement deposits occur frequently along the sediment profile. Mineral magnetic investigation made on sediments enclosed in core catchers suggests that magnetic carrier in these sediments is partly maghemitized Ti-rich pseudo-single domain magnetite. Its detrital origin can be shown by mineral magnetic measurements and SEM-EDS analyses performed on mini-sized cylindrical rock samples, polished rock sections and creek sediments. The intensity of the natural remanent magnetization in the sediments is high with a range from about 1 to 1000 mA m-1. Most of the sediments carry a stable magnetization interpreted as primary depositional remanent magnetization. Characteristic inclination data show alternating intervals of steep positive and negative inclinations that are used to assign magnetic polarity to the lake sediment profile. This is a rather straightforward procedure owing to the mainly high quality of data. The Matuyama/Gauss (M/G) (2.608 Ma) and Brunhes/Matuyama (B/M) (0.780 Ma) reversals were recognized in the sediments. The Mammoth and Kaena reversed subchrons were identified during the Gauss chron, and the Olduvai and Jaramillo normal subchrons as well as the Réunion and Cobb Mountain cryptochrons were identified during the Matuyama chron. Sediments also provide a record of the Olduvai precursor and Intra-Jaramillo geomagnetic excursions. Sediment deposition rate is highest at the base of the sequence laid down in the early Gauss chron, when the

  19. Magnetostratigraphy of sediments from Lake El'gygytgyn ICDP Site 5011-1: paleomagnetic age constraints for the longest paleoclimate record from the continental Arctic

    NASA Astrophysics Data System (ADS)

    Haltia, E. M.; Nowaczyk, N. R.

    2013-09-01

    Paleomagnetic measurements were performed on sediments drilled from ICDP Site 5011-1 in Lake El'gygytgyn (67°30' N, 172°05' E) located in Far East Russian Arctic. The lake fills partly a crater formed by a meteorite impact 3.58 ± 0.04 Ma ago. Sediments from three parallel cores (5011-1A, 5011-1B and 5011-1C), recovered from the middle part of the lake, yielded a total of 355 m of sediment. Sediments are characterized by variable lithology, where intervals of homogenous and laminated sediments alternate, and mass movement deposits of variable thickness occur frequently along the sediment profile. Mineral magnetic investigation made on sediments enclosed in core catchers suggests that magnetic carrier in these sediments is partly maghemitized Ti-rich pseudo-single domain magnetite. Its detrital origin could be shown by mineral magnetic measurements and SEM-EDS analyses performed on mini-sized cylindrical rock samples, polished rock sections, creek sediments and magnetic extracts prepared from them. The intensity of the natural remanent magnetization (NRM) in the sediments is mainly high with a range from about 1 to 1000 mA m-1. Most of the sediments carry a stable magnetization component interpreted as primary depositional remanent magnetization. Characteristic inclination data show alternating intervals of steep positive and negative inclinations that were used to assign magnetic polarity to the lake sediment profile. This was a rather straightforward procedure owing to the mainly high quality of data. The Matuyama/Gauss (2.608 Ma) and Brunhes/Matuyama (0.780 Ma) reversals were recognized in the sediments. Furthermore, during the Gauss chron the Mammoth and Kaena reversed subchrons, and during the Matuyama, the Olduvai and Jaramillo normal subchrons, as well as the Réunion and Cobb Mountain cryptochrons were identified. Sediment deposition rate is highest at the base of the sequence laid down in the beginning of Gauss chron, when deposition rate is approximately

  20. 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 ...

  1. Wilms' Tumor

    MedlinePlus

    ... team and have training in child development, recreation, psychology or social work. If your child must remain ... conditions/wilms-tumor/basics/definition/CON-20043492 . Mayo Clinic Footer Legal Conditions and Terms Any use of ...

  2. Tumor Grade

    MedlinePlus

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... much of the tumor tissue has normal breast (milk) duct structures Nuclear grade : an evaluation of the ...

  3. Spinal tumor

    MedlinePlus

    ... Livingstone; 2014:chap 49. Read More Brain tumor - children Hodgkin lymphoma Metastasis Spinal cord trauma Review Date 8/15/2016 Updated by: Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review ...

  4. Wilms tumor

    MedlinePlus

    ... a type of kidney cancer that occurs in children. Causes WT is the most common form of childhood kidney cancer. The exact cause of this tumor in most children is unknown. A missing iris of the eye ( ...

  5. Pituitary tumor

    MedlinePlus

    ... enough of its hormones. This condition is called hypopituitarism . The causes of pituitary tumors are unknown. Some ... Cyst Endocrine glands Gigantism Growth hormone test Hyperthyroidism Hypopituitarism Multiple endocrine neoplasia (MEN) I Prolactin blood test ...

  6. American Brachytherapy Society Task Group Report: Combined external beam irradiation and interstitial brachytherapy for base of tongue tumors and other head and neck sites in the era of new technologies.

    PubMed

    Takácsi-Nagy, Zoltán; Martínez-Mongue, Rafael; Mazeron, Jean-Jacques; Anker, Cristopher James; Harrison, Louis B

    Irradiation plays an important role in the treatment of cancers of the head and neck providing a high locoregional tumor control and preservation of organ functions. External beam irradiation (EBI) results in unnecessary radiation exposure of the surrounding normal tissues increasing the incidence of side effects (xerostomy, osteoradionecrosis, and so forth). Brachytherapy (BT) seems to be the best choice for dose escalation over a short treatment period and for minimizing radiation-related normal tissue damage due to the rapid dose falloff around the source. Low-dose-rate BT is being increasingly replaced by pulsed-dose-rate and high-dose-rate BT because the stepping source technology offers the advantage of optimizing dose distribution by varying dwell times. Pulsed-dose and high-dose rates appear to yield local control and complication rates equivalent to those of low-dose rate. BT may be applied alone; but in case of high risk of nodal metastases, it is used together with EBI. This review presents the results and the indications of combined BT and EBI in carcinoma of the base of tongue and other sites of the head and neck region, as well as the role BT plays among other-normal tissue protecting-modern radiotherapy modalities (intensity-modulated radiotherapy, stereotactic radiotherapy) applied in these localizations.

  7. 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

  8. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF LABOR 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...

  9. Introducing Computed Tomography Standards for Age Estimation of Modern Australian Subadults Using Postnatal Ossification Timings of Select Cranial and Cervical Sites(.).

    PubMed

    Lottering, Nicolene; MacGregor, Donna M; Alston, Clair L; Watson, Debbie; Gregory, Laura S

    2016-01-01

    Contemporary, population-specific ossification timings of the cranium are lacking in current literature due to challenges in obtaining large repositories of documented subadult material, forcing Australian practitioners to rely on North American, arguably antiquated reference standards for age estimation. This study assessed the temporal pattern of ossification of the cranium and provides recalibrated probabilistic information for age estimation of modern Australian children. Fusion status of the occipital and frontal bones, atlas, and axis was scored using a modified two- to four-tier system from cranial/cervical DICOM datasets of 585 children aged birth to 10 years. Transition analysis was applied to elucidate maximum-likelihood estimates between consecutive fusion stages, in conjunction with Bayesian statistics to calculate credible intervals for age estimation. Results demonstrate significant sex differences in skeletal maturation (p < 0.05) and earlier timings in comparison with major literary sources, underscoring the requisite of updated standards for age estimation of modern individuals.

  10. 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

  11. 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

  12. Spinal Cord Tumor

    MedlinePlus

    Spinal cord tumor Overview By Mayo Clinic Staff A spinal tumor is a growth that develops within your ... as vertebral tumors. Tumors that begin within the spinal cord itself are called spinal cord tumors. There are ...

  13. What Is Wilms Tumor?

    MedlinePlus

    ... Treatment? Wilms Tumor About Wilms Tumor What Is Wilms Tumor? Cancer starts when cells in the body begin ... live normal, healthy lives with just one kidney. Wilms tumors Wilms tumors are the most common cancers in ...

  14. 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.

  15. 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

  16. Computed tomography of Krukenberg tumors

    SciTech Connect

    Cho, K.C.; Gold, B.M.

    1985-08-01

    Computed tomography (CT) of three patients with Kurkenberg tumor was reviewed retrospectively. CT showed large, lobulated, multicystic masses with soft-tissue components, indistinguishable from primary ovarian carcinoma. Much has been written about metastatic ovarian tumor, but this is the first report in the radiologic literature about their CT features. The authors emphasize the importance of recognizing the ovary as a frequent site of metastases and the proper approach to this problem. In patients with a history of colon or gastric carcinoma, the mixed cystic and solid ovarian mass on CT should be regarded as metastatic tumor until proven otherwise. A careful search for gastrointestinal tract signs or symptoms should be done in any patient with a pelvic tumor. When CT is done for evaluation of ovarian tumor, the stomach and colon should be carefully evaluated, and the ovaries routinely examined in the preoperative CT staging of gastric or colon carcinoma.

  17. Minor intraoral salivary gland tumors: a clinical-pathological study

    PubMed Central

    Sarmento, Dmitry José de Santana; Morais, Maria de Lourdes Silva de Arruda; Costa, Antonio de Lisboa Lopes; da Silveira, Éricka Janine Dantas

    2016-01-01

    ABSTRACT Objective To evaluate the clinical-pathological profile of patients with minor salivary gland neoplasms. Methods A retrospective study of specific cases diagnosed as benign and malignant tumors of the minor salivary glands was performed. The data were collected from medical records of patients seen at a hospital over a period of 15 years. The sample was made up of 37 cases. For the pathological study, slides containing 5μm thick sections stained with hematoxylin and eosin were used. The data were tabulated using descriptive statistics. Results Malignant neoplasms represented 70.3% of cases. The mucoepidermoid carcinoma was the most common neoplasm (45.9%), followed by pleomorphic adenoma (24.4%). Most patients were female (70.3%), aged between 71 and 80 years. The palate (67.6%) and the retromolar region (10.8%) were the most affected sites. Conclusion Mucoepidermoid carcinoma was the most common tumor in minor salivary glands. These tumors are more common in females aged over 40 years. The palate was the most common affected site. PMID:28076598

  18. Platelets effects on tumor growth.

    PubMed

    Goubran, Hadi A; Stakiw, Julie; Radosevic, Mirjana; Burnouf, Thierry

    2014-06-01

    Unlike other blood cells, platelets are small anucleate structures derived from marrow megakaryocytes. Thought for almost a century to possess solely hemostatic potentials, platelets, however, play a much wider role in tissue regeneration and repair and interact intimately with tumor cells. On one hand, tumor cells induce platelet aggregation (TCIPA), known to act as the trigger of cancer-associated thrombosis. On the other hand, platelets recruited to the tumor microenvironment interact, directly, with tumor cells, favoring their proliferation, and, indirectly, through the release of a wide palette of growth factors, including angiogenic and mitogenic proteins. In addition, the role of platelets is not solely confined to the primary tumor site. Indeed, they escort tumor cells, helping their intravasation, vascular migration, arrest, and extravasation to the tissues to form distant metastasis. As expected, nonspecific or specific inhibition of platelets and their content represents an attractive novel approach in the fight against cancer. This review illustrates the role played by platelets at primary tumor sites and in the various stages of the metastatic process.

  19. 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

  20. Central nervous system tumors in Mexican children.

    PubMed

    De la Torre Mondragón, L; Ridaura Sanz, C; Reyes Mujica, M; Rueda Franco, F

    1993-08-01

    Five hundred and seventy primary central nervous system (CNS) tumors from the Department of Pathology at the National Institute of Pediatrics in Mexico City, collected from 1970 to 1989, were histologically reclassified in order to find out their relative incidence as well as their outstanding features. With this, we could establish a frame of reference for our local population, contributing to the epidemiological analysis of these entities. All the tumors were examined independently by two pathologists (C.R. and M.R.), using the classification of Rorke et al. Histological type, patient age and sex, and tumor location were analyzed. CNS tumors were the secondmost frequently encountered solid tumors, after lymphomas, and were increasing in incidence at a rate of 2.2 annually. Children in the age group 0-9 years were most often affected, and there was a predominance of male patients. Astrocytoma and medulloblastoma were the most common tumor types. The infratentorial region was the most frequent tumor location in the 2- to 9-year age group. By contrast, in the under 2-year-olds a supratentorial location was more frequent, and the incidence of germ cell tumors was proportionally high. In general, some histological types seemed to be associated with particular age groups. Although we found primitive neuroectodermal tumors to be the fifth most common at all ages (except for medulloblastoma), many other authors do not report a similar finding.

  1. 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.

  2. Final Technical Report: The effects of climate, forest age, and disturbance history on carbon and water processes at AmeriFlux sites across gradients in Pacific Northwest forests

    SciTech Connect

    Law, Beverly E.

    2016-12-03

    Investigate the effects of disturbance and climate variables on processes controlling carbon and water processes at AmeriFlux cluster sites in semi-arid and mesic forests in Oregon. The observations were made at three existing and productive AmeriFlux research sites that represent climate and disturbance gradients as a natural experiment of the influence of climatic and hydrologic variability on carbon sequestration and resulting atmospheric CO2 feedback that includes anomalies during the warm/ dry phase of the Pacific Decadal Oscillation.

  3. Pituitary Tumors

    MedlinePlus

    ... almost always benign (not cancerous), but can cause hormonal imbalances and interfere with the normal function of the pituitary gland. Because the pituitary affects so many functions of the body, ... the tumor mass or hormonal changes (either too much or too little hormone). ...

  4. Sleep and Aging: Insomnia

    MedlinePlus

    ... this page please turn Javascript on. Sleep and Aging Insomnia Insomnia is the most common sleep complaint ... us | Customer Support | site map National Institute on Aging | U.S. National Library of Medicine | National Institutes of ...

  5. 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-.

  6. Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review.

    PubMed

    Shin, Young Duck; Lee, Seul Kee; Kim, Kyu Sun; Park, Mi Ja; Kim, Joo Heon; Yim, Hyun Sun; Choi, Young Jin

    2014-01-08

    There have been some reports of coincidental presentation of breast carcinoma and phyllodes tumor in the same breast. Most of the cases were carcinoma that arose from a phyllodes tumor with a histologically identified transitional area, and they behaved less aggressively than the usually encountered carcinoma. Collision tumors are rare clinical entities in which two histologically distinct tumor types show involvement at the same site. The occurrence of these tumors in the breast is extremely rare. Here, we report a case of 45-year-old woman who had both invasive ductal carcinoma as the finding of inflammatory carcinoma and a malignant phyllodes tumor in the same breast. There was no evidence of a transitional area between the phyllodes tumor and the invasive ductal carcinoma. To our knowledge, this is the first report of a collision tumor of inflammatory breast carcinoma coincident with a malignant phyllodes tumor in same breast.

  7. A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702)

    PubMed Central

    Stokland, Tore; Liu, Jo-Fen; Ironside, James W.; Ellison, David W.; Taylor, Roger; Robinson, Kathryn J.; Picton, Susan V.; Walker, David A.

    2010-01-01

    The purpose of this study was to identify risk factors for the progression of low-grade glioma in children from a large population-based cohort. Patient and tumor details of a national cohort of children with low-grade glioma, recruited into an international multidisciplinary clinical strategy, were subjected to univariate and multivariate analyses of progression-free survival and overall survival. From the cohort of 798 patients, 639 patients were eligible, with a median age 6.71 years (0.26–16.75 years); 49% were males; 15.9% had neurofibromatosis type 1, 63.7% pilocytic astrocytoma, 5.9% fibrillary astrocytoma, 4.2% mixed neuronal-glial tumors, and 3.6% others; 21.1% were diagnosed clinically. Anatomically implicated were 31.6% cerebellum, 24.6% chiasma/hypothalamus, 16.0% cerebral hemispheres, 9.9% brain stem, 6.1% other supratentorial midline structures, 5.9% optic nerve only, 4.5% spinal cord, and 1.4% others. The 5-year overall survival and progression-free survival in the whole cohort were 94.6% and 69.4%, respectively. There was a significant association between age and site (P < .001) and extent of tumor resection and site (P < .001). Multivariate analysis identified young age, fibrillary astrocytoma, and extent of surgical resection as significant independent risk factors for progression. Hypothalamic/chiasmatic tumors demonstrated the most sustained tendency to progress. In conclusion, the influence of age and anatomical site upon the risk of tumor progression suggests that these factors strongly influence tumor behavior for the majority of pilocytic tumors. Age <1 year and 1–5 years, fibrillary histology, completeness of resection, and chiasmatic location are candidates for stratification in future studies. PMID:20861086

  8. 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

  9. "Cancer tumor".

    NASA Astrophysics Data System (ADS)

    Bronshtehn, V. A.

    The title is a phrase borrowed from a speech by a Leningrad pressman, V. E. Lvov, who called upon those attending a theoretical conference on ideological issues in astronomy held by the Leningrad Branch of the All-Union Astronomic and Geodetic Society (13 - 4 December 1948), "to make a more radical emphasis on the negative role of relativistic cosmology which is a cancer tumor disintegrating the contemporary astronomy theory, and a major ideological enemy of a materialist astronomy".

  10. Primary spinal tumors in childhood: A single institution 15 year experience

    PubMed Central

    Hung, Po-Cheng; Wu, Chieh-Tsai; Jaing, Tang-Her; Sheen, Jiunn-Ming; Chou, Ming-Liang; Lin, Kuang-Lin

    2016-01-01

    Background: Pediatric primary spinal tumors (PST) are fairly uncommon, with little available data regarding incidence and outcomes. Materials and Methods: We conducted a retrospective review of the 22 consecutive patients less than 18 years old diagnosed with PST between March 1997 and May 2011 and treated at Chang Gung Children Hospital. All patients had undergone magnetic resonance imaging (MRI) for pre-operative evaluation and operations for PST. The extent of tumor removal was assessed by surgical report by the neurosurgeon or by post-operative MRI if available. Results: Ten of them had intramedullary tumors and 12 had intradural extramedullary tumors. All patients were treated with surgery to the primary site. A total of 15 patients underwent gross total tumor resection and seven patients received post-operative radiotherapy. Five patients received adjuvant chemotherapy for their primary tumor. Fourteen patients (64%) survived from study entry without tumor progression. Conclusions: PST encompassed a diverse group of pathologic entities that differ markedly based on the location and age of the children. Total resection of pediatric PST in children could be performed with acceptable risk and satisfactory long-term results. PMID:27695552

  11. 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.

  12. Epigenetic Regulation of Ovarian Tumor Immunity

    DTIC Science & Technology

    2010-11-01

    immunity PRINCIPAL INVESTIGATOR: Protul A. Shrikant, Ph.D. CONTRACTING ORGANIZATION : Health Research Inc., Roswell Park Cancer...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Roswell Park Cancer...intraperitoneal injection on day 10 post-tumor challenge. 2. The cells harvested from the tumor draining LN’s, spleen and the tumor site starting on day 2

  13. 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, ...

  14. 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 ...

  15. 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 ...

  16. Adrenal Gland Tumors: Statistics

    MedlinePlus

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  17. 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 ...

  18. Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8+ T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer

    PubMed Central

    Vassilev, L; Ranki, T; Joensuu, T; Jäger, E; Karbach, J; Wahle, C; Partanen, K; Kairemo, K; Alanko, T; Turkki, R; Linder, N; Lundin, J; Ristimäki, A; Kankainen, M; Hemminki, A; Backman, C; Dienel, K; von Euler, M; Haavisto, E; Hakonen, T; Juhila, J; Jäderberg, M; Priha, P; Vuolanto, A; Pesonen, S

    2015-01-01

    Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8+ lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8+ T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study. PMID:26140248

  19. Abdominal tumors in children

    PubMed Central

    Oh, Chaeyoun; Youn, Joong Kee; Han, Ji-Won; Kim, Hyun-Young; Jung, Sung-Eun

    2016-01-01

    Abstract The use of minimally invasive surgery (MIS) in pediatric patients has been steadily increasing in recent years. However, its use for diagnosing and treating abdominal tumors in children is still limited compared with adults, especially when malignancy is a matter of debate. Here, we describe the experience at our center with pediatric abdominal tumors to show the safety and feasibility of MIS. Based on a retrospective review of patient records, we selected for study those pediatric patients who had undergone diagnostic exploration or curative resection for abdominal tumors at a single center from January 2010 through August 2015. Diagnostic exploration for abdominal tumors was performed in 32 cases and curative resection in 173 cases (205 operations). MIS was performed in 11 cases of diagnostic exploration (34.4%) and 38 cases of curative resection (21.9%). The mean age of the children who underwent MIS was 6.09 ± 5.2 years. With regard to diagnostic exploration, patient characteristics and surgical outcomes were found to be similar for MIS and open surgery. With regard to curative resection, however, the mean age was significantly lower among the patients who underwent open surgery (4.21 ± 4.20 vs 6.02 ± 4.99 for MIS, P = 0.047), and the proportion of malignancies was significantly higher (80% vs 39.4% for MIS, P < 0.001). MIS compared favorably with open surgery with respect to the rate of recurrence (6.7% vs 35.1%, P = 0.035), the rate of intraoperative transfusions (34.2% vs 58.5%, P = 0.01), the median amount of blood transfused (14 vs 22 mL/kg, P = 0.001), and the mean number of hospital days (4.66 ± 2.36 vs 7.21 ± 5.09, P < 0.001). Complication rates did not differ significantly between the MIS and open surgery groups. The operation was converted to open surgery in 3 cases (27.2%) of diagnostic MIS and in 5 cases (13.1%) of curative MIS. MIS was found to be both feasible and effective for the

  20. Gonadal germ cell tumors in children and adolescents

    PubMed Central

    Cecchetto, Giovanni

    2014-01-01

    Pediatric germ cell tumors (GCT) are rare tumors: 80% are benign, 20% malignant (2-3% of all malignant pediatric tumors). The gonadal sites (ovary and testis) account for 40% of cases. Ovarian GCTs: Represent 30% of GCTs and 70% of neoplastic ovarian masses, being the most common ovarian neoplasms in children and teenagers. Benign and immature forms (teratomas) constitute about 80% of all ovarian GCTs, malignant forms represent 20% increasing during adolescence. The most common malignant entity in children is the yolk sac tumors (YST); dysgerminoma is frequent during adolescence and being bilateral in 10% of cases. Presentation is similar in malignant and benign lesions; abdominal pain (70-80%) and lower abdominal mass are common symptoms. Evaluation of alpha-fetoprotein (αFP) or beta subunit of human chorionic gonadotropin (βHCG) is essential to address the nature of the tumors: Their elevation means presence of malignancy. Surgery includes intraoperative staging procedures and requires ovariectomy or ovarosalpingectomy for malignant lesions, but may be conservative in selected benign tumors. Since malignant GCTs are very chemosensitive, primary chemotherapy is recommended in metastatic or locally advanced tumors. Testicular GCT: Represent 10% of pediatric GCT, and about 30% of malignant GCT with two age peaks: Children <3 years may experience mature teratoma and malignant GCTs, represented almost exclusively by YST, while adolescents may also show seminomas or other mixed tumors. The main clinical feature is a painless scrotal mass. Surgery represents the cornerstone of the management of testicular GCTs, with an inguinal approach and a primary high orchidectomy for malignant tumors, while a testis-sparing surgery can be considered for benign lesions. A retroperitoneal lymph node (LN) biopsy may be necessary to define the staging when the involvement of retroperitoneal LN is uncertain at imaging investigations. Conclusion: Patients with gonadal malignant GCTs

  1. WWOX: A fragile tumor suppressor

    PubMed Central

    Schrock, Morgan S

    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, 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 a 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 the human WWOX locus 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 chromosomal fragile sites 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

  2. Loss of calcitonin receptors: A genetically transmitted defect in rats with high incidence of C-cell tumors

    SciTech Connect

    Bouizar, Z.; Minvielle, S.; Treilhou-Lahille, F.; Rostene, W.H.; Pidoux, E.; Feingold, N.; Milhaud, G.; Moukhtar, M.S. )

    1989-09-15

    C-cell tumors (medullary thyroid carcinoma) occur in humans and several other mammalian species. This tumor develops spontaneously with a high incidence (50%) in old Wag/Rij (Wistar-derived strain) rats. We have recently shown that calcitonin binding sites, which are present in the Wistar rats, are lost from renal medulla of the Wag/Rij rats before they reach the age of 1 month. In the present work, we investigated the distribution of calcitonin binding sites in the kidneys of first and second generation hybrids of Wistar x Wag/Rij rats. The absence of calcitonin binding sites from the renal medullas of 25% of F2 hybrids indicates that the deficiency is inherited in a Mendelian fashion and opens the way to establishing inbred strains lacking renal medullary calcitonin binding sites.

  3. Evaluation of the Olduvai subchron in the Orce ravine (SE Spain). Implications for Plio-Pleistocene mammal biostratigraphy and the age of Orce archeological sites

    NASA Astrophysics Data System (ADS)

    Gibert, L.; Scott, G.; Ferràndez-Cañadell, C.

    2006-03-01

    The Barranco de Orce (BO) section in the Baza basin (SE Spain) exposes several fossiliferous layers (O-1 to O-7) with Plio-Pleistocene micro- and macromammals. Biostratigraphic and magnetostratigraphic data from this and other sections in the basin have been extensively used to calibrate the Plio-Pleistocene chronology based on mammal biozonations. Because of its stratigraphic and geographic proximity, the BO section has also been used to date the paleontological and archeological sites of Barranco León, Fuentenueva-3 and Venta Micena. This study shows that the BO section crosses a mega-landslide that produces partial repetitions of the sedimentary sequence. The seven fossiliferous layers are actually the repetition of only two (O-6 and O-7) which are found in situ in the upper part of the ravine. New paleomagnetic results demonstrate the presence of Reverse magnetization throughout this section, contradicting the Normal event previously reported and assigned to the 'Olduvai' subchron (C2n). Published and new magnetostratigraphic data show that all archeological and paleontological sites in the Orce area are within a Reverse magnetochron, presumably C1r.2r (late Matuyama). The use of BO in the magnetobiostratigraphical calibration of the Pliocene/Pleistocene boundary for western Europe is not advised.

  4. Structure shows that a glycosaminoglycan and protein recognition site in factor H is perturbed by age-related macular degeneration-linked single nucleotide polymorphism.

    PubMed

    Herbert, Andrew P; Deakin, Jon A; Schmidt, Christoph Q; Blaum, Bärbel S; Egan, Claire; Ferreira, Viviana P; Pangburn, Michael K; Lyon, Malcolm; Uhrín, Dusan; Barlow, Paul N

    2007-06-29

    A common single nucleotide polymorphism in the factor H gene predisposes to age-related macular degeneration. Factor H blocks the alternative pathway of complement on self-surfaces bearing specific polyanions, including the glycosaminoglycan chains of proteoglycans. Factor H also binds C-reactive protein, potentially contributing to noninflammatory apoptotic processes. The at risk sequence contains His (rather than Tyr) at position 402 (384 in the mature protein), in the seventh of the 20 complement control protein (CCP) modules (CCP7) of factor H. We expressed both His(402) and Tyr(402) variants of CCP7, CCP7,8, and CCP6-8. We determined structures of His(402) and Tyr(402) CCP7 and showed them to be nearly identical. The side chains of His/Tyr(402) have similar, solvent-exposed orientations far from interfaces with CCP6 and -8. Tyr(402) CCP7 bound significantly more tightly than His(402) CCP7 to a heparin affinity column as well as to defined-length sulfated heparin oligosaccharides employed in gel mobility shift assays. This observation is consistent with the position of the 402 side chain on the edge of one of two glycosaminoglycan-binding surface patches on CCP7 that we inferred on the basis of chemical shift perturbation studies with a sulfated heparin tetrasaccharide. According to surface plasmon resonance measurements, Tyr(402) CCP6-8 binds significantly more tightly than His(402) CCP6-8 to immobilized C-reactive protein. The data support a causal link between H402Y and age-related macular degeneration in which variation at position 402 modulates the response of factor H to age-related changes in the glycosaminoglycan composition and apoptotic activity of the macula.

  5. Decline of tactile acuity in aging: a study of body site, blood flow, and lifetime habits of smoking and physical activity.

    PubMed

    Stevens, Joseph C; Alvarez-Reeves, Marty; Dipietro, Loretta; Mack, Gary W; Green, Barry G

    2003-01-01

    Tactile acuity of 60 older subjects (> or = 65 years) and 19 younger subjects (18-28 years) was assessed by two-point gap thresholds at the upper and lower surfaces of the forefinger, at the upper and lower surfaces of the feet, and at the volar surface of the forearm. The older subjects were assigned to one of four groups of 15 subjects each, depending on reported lifetime habits of physical activity and smoking: (1) active smokers, (2) active nonsmokers, (3) inactive smokers, and (4) inactive nonsmokers. Peripheral blood flow was assessed at the forefinger, foot, and forearm by means of laser-Doppler imaging and skin temperature recordings, under resting conditions and during and after a 5-min exposure to mild cooling (28 degrees C). Consistent with previous studies, tactile acuity thresholds in the foot and finger averaged about 80% higher in the older subjects than in the younger subjects, but only about 22% higher in the forearm. Although the upper surface of the fingertip was more sensitive than the lower surface in both younger and older subjects, the age-related decline in tactile acuity was nearly identical on both sides of the finger and foot. The latter finding refutes the hypothesis that the larger effect of aging in the extremities results from greater physical wear and tear on the contact surfaces of the hands and feet. Self-reported lifetime histories of physical activity and smoking were not significantly associated with measures of cutaneous blood flow or tactile thresholds. Possible reasons for this lack of association are discussed, including the inherent limitations of testing only healthy older subjects, and the concept of "successful aging".

  6. 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

  7. Spectrum of pediatric tumors diagnosed by fine-needle aspiration cytology

    PubMed Central

    Shirian, Sadegh; Daneshbod, Yahya; Haghpanah, Sezaneh; Khademi, Bijan; Noorbakhsh, Farshid; Ghaemi, Amir; Mosayebi, Ziba

    2017-01-01

    Abstract Pediatric tumors differ markedly from adult tumors in their nature, distribution, and prognosis. In this 10-year retrospective study, we present our experience with fine-needle aspiration (FNA) in pediatric patients 18 years of age and younger and correlate relationship between gender with organ, diagnosis, malignancy, and age. In our study, FNA material of pediatric tumors or masses with 18 years aged and younger were analyzed retrospectively. All FNAs in pediatric patients during this time period were identified and analyzed for age, gender, cytologic diagnosis, and site of aspiration. A total 1000 FNAs were performed from January 2007 to October 2015 in 499 children. Regardless the gender, the most frequently aspirated organ was lymph node, comprising 129 of the 499 cases followed by thyroid (112), neck cyst (79), and parotid (35) cases. The majority of the cases were diagnosed as benign lesions (436 of 499 cases). Other 63 cases comprising 40 female and 23 male cases had malignant lesions. There was significant age difference between people with or without malignancy. In malignant cases, there was a significant difference between the age on males and females. In regard to gender and diagnosis, cytologic diagnosis was stratified into 9 broad diagnostic categories: lymphadenitis, benign and malignant thyroid, cyst contents, benign breast, benign and malignant salivary, and negative for malignancy. In conclusion, our study supports the use of FNA cytology (FNAC) in lesions of various anatomic sites in the children less than 18 years old. As a simple, minimally invasive, and rapid procedure, cytopathologists can reliably utilize FNAC in children. The mean age of children receiving a malignant diagnosis was significantly higher than that of benign lesions. The mean age of malignancy in boys is significantly lower than that of girls with malignancy. PMID:28178123

  8. Clinical and pathologic relevance of p53 index in canine osseous tumors.

    PubMed

    Loukopoulos, P; Thornton, J R; Robinson, W F

    2003-05-01

    The clinicopathologic value of the immunohistochemical (IHC) expression of p53 protein was evaluated in 167 canine osseous tumors. p53 staining frequency and intensity in tumor cells was expressed as a p53 index. p53 index was significantly higher in osteosarcomas than in other sarcomas, chondrosarcoma, multilobular tumor of bone, and tumors initially misdiagnosed as osteosarcomas as well as in appendicular versus axial and in distal versus proximal osteosarcomas. A strong correlation is demonstrated between the p53 index and a range of clinicopathologic parameters in osteosarcoma, including the tumor site, histologic grade and score, mitotic index, degree of tumor necrosis, and pleomorphism. Chondroblastic osteosarcomas had significantly higher and telangiectatic osteosarcomas significantly lower p53 index than did osteosarcomas belonging to other histopathologic subtypes, a fact that tends to reinforce the perception of these osteosarcomas as distinct clinicopathologic entities. Entire males had higher p53 index than did neutered males. p53 index was higher in Rottweilers than in Great Danes and Terriers, confirming breed susceptibilities to osteosarcoma. p53 index showed no association with age, primary or secondary site status, or the presence of metastases or other tumor types. Biopsy samples had a higher p53 index than did postmortem samples, either because of differences in sample processing or the possibility that p53 overexpression is more evident at the earlier stages of osteosarcoma pathogenesis, presumably represented by the biopsy material. IHC examination for p53 and the derived index has the potential to be used as an additional diagnostic tool and prognostic indicator for osseous tumors.

  9. Cartilaginous Tumors of the Larynx and Trachea in the Dog: Literature Review and 10 Additional Cases (1995-2014).

    PubMed

    Ramírez, G A; Altimira, J; Vilafranca, M

    2015-11-01

    Cartilaginous tumors of the larynx and trachea are uncommon in the dog. The authors describe 10 cases diagnosed between 1995 and 2014 and review 16 cases in the literature. Seven of our cases were tracheal and 3 were laryngeal. Two of the laryngeal tumors were chondromas, which have not been previously reported in this site. The third laryngeal tumor was a myxochondroma. Of the 7 tracheal tumors, 6 arose from the ventral tracheal wall, including 2 that were extraluminal. Tracheal tumor types included chondrosarcoma (n = 3), chondroma (n = 2), and osteochondroma (n = 2). All of the laryngeal tumors and 5 of 7 of the tracheal tumors occurred in adult dogs (aged 5-11 years). The 2 tracheal osteochondromas were in young dogs (3-4 months) and were intrathoracic, while the remaining tracheal tumors were cervical. Surgical excision had a good outcome in most cases. Combining our 10 cases with the 16 previously reported cases showed that 6 (27%) of the affected dogs were Arctic breeds (Alaskan Malamute or Siberian Husky) suggesting a predisposition in this type of dog.

  10. Brain tumor immunotherapy: an immunologist's perspective.

    PubMed

    Lampson, Lois A

    2003-01-01

    Key concepts in brain tumor immunotherapy are reviewed. "Immunotherapy" can refer to a fully-developed, tumor-specific immune response, or to its individual cellular or molecular mediators. The immune response is initiated most efficiently in organized lymphoid tissue. After initiation, antigen-specific T lymphocytes (T cells) survey the tissues--including the brain. If the T cells re-encounter their antigen at a tumor site, they can be triggered to carry out their effector functions. T cells can attack tumor in many ways, directly and indirectly, through cell-cell contact, secreted factors, and attraction and activation of other cells, endogenous or blood-borne. Recent work expands the list of candidate tumor antigens: they are not limited to cell surface proteins and need not be absolutely tumor-specific. Once identified, tumor antigens can be targeted immunologically, or in novel ways. The immune response is under complex regulatory control. Most current work aims to enhance initiation of the response (for example, with tumor vaccines), rather than enhancing the effector phase at the tumor site. The effector phase includes a rich, interactive set of cells and mediators; some that are not usually stressed are of particular interest against tumor in the brain. Within the brain, immune regulation varies from site to site, and local neurochemicals (such as substance P or glutamate) can contribute to local control. Given the complexity of a tumor, the brain, and the immune response, animal models are essential, but more emphasis should be given to their limitations and to step-by-step analysis, rather than animal "cures".

  11. C.N.S. tumors in eastern Saudi Arabia.

    PubMed

    Ibrahim, A W

    1992-01-01

    In Saudi Arabia, there were no attempts previously to describe a population based frequency or incidence, particularly so the age adjusted incidence of various CNS tumors. This paper presents the primary CNS tumors from a population based tumor registry over two years period, from January 1987 till December 1988. There was a total of 85 cases representing 5.4% of the total captured cases (1,568 cases of malignant tumors at all sites). The population of the Eastern Province is estimated to be 1.37 million, the Saudis forming 80% of the total population. Out of the 85 cases captured over two years, there were 64 cases diagnosed in indigenous Saudi population forming 75%. The remaining occurred in non-Saudi residents. The male/female ratio in Saudis was 1:1.1 with a slight predominance of the female, while the reverse is true in the non-Saudis (2:1). The total captured cases per annum is 43, making the incidence of primary CNS neoplasms in the Eastern Province of Saudi Arabia 3.1/100,000 of all the population and 2.9/100,000 in Saudi nationals. Comparing this incidence to the international figure, it was clear that it is far less than the incidence reported from North America and Europe, particularly in the Caucasian population, but similar to incidences reported in the Chinese, black Americans, Romanians and Yugoslavians, but certainly less than the Ashkenazi or Safari Jews, and slightly higher than the incidence reported in Japan and Southeast Asia. Malignant brain tumors of various types dominated the primary CNS neoplasms reported over these two years forming 69% of the cases and 52% of the primary brain tumors.

  12. 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

  13. Pío del Río-Hortega: A Visionary 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

  14. 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.

  15. 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

  16. Rectal and appendiceal inflammatory myofibroblastic tumors.

    PubMed

    Khoddami, Maliheh; Sanae, Shahram; Nikkhoo, Bahram

    2006-07-01

    Inflammatory myofibroblastic tumors are neoplasms characterized by spindle cell proliferation and a fiboinflammatory vascular stroma. Herein, we presented the successful treatment of a rectal inflammatory myofibroblastic tumor in an 11-year-old boy who presented with diarrhea and abdominal pain of 1(1/2) months duration and an appendiceal inflammatory myofibroblastic tumor in a 29-year-old man presented with recurrent abdominal pain of two months duration with associated tenderness and rebound tenderness in the right lower abdomen. Histologically, our cases had inflammatory myofibroblastic tumors very similar to that of other sites; the spindle cells were positive for vimentin and muscle-specific actin.

  17. Neck Rhabdoid Tumors: Clinical Features and Consideration of Autologous Stem Cell Transplant.

    PubMed

    Wolfe, Adam D; Capitini, Christian M; Salamat, Shahriar M; DeSantes, Kenneth; Bradley, Kristin A; Kennedy, Tabassum; Dehner, Louis P; Patel, Neha J

    2017-04-03

    Extrarenal malignant rhabdoid tumors (MRT) have a poor prognosis despite aggressive therapy. Adding high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) as consolidative therapy for MRT is controversial. We describe 2 patients, age 13 years and 19 months, with unresectable neck MRT. After chemotherapy and radiotherapy, both underwent HDC-ASCR and remain in remission over 4 years later. We reviewed all published cases of neck MRT, and found poorer outcomes and more variable age of presentation and time to progression than MRT at other sites. Neck MRT may represent a higher-risk subset of MRT, and addition of HDC-ASCR merits consideration.

  18. 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

  19. The rare malignancy of the hepatobiliary system: ampullary carcinoid tumor.

    PubMed

    Ozsoy, Mustafa; Ozsoy, Yucel; Canda, Aras Emre; Nalbant, Olcay Ak; Haskaraca, Fatih

    2011-01-01

    Introduction. Carcinoid tumors are low-grade tumors originating from endoderm and mostly involving the gastrointestinal system. However; they may be seen in any site within the gastrointestinal system. Case Presentation. A 69-year-old female patient. The results of blood tests were observed to be consistent with obstructive jaundice. A mass appearance was not encountered on tomographic examination. Papilla that was tumor-like macroscopically was seen in the second part of the duodenum in diagnostic endoscopy. Pylorus-preserving pancreaticoduodenectomy surgical procedure was applied. On pathological examination of the mass, a tumoral mass was detected in ampulla vateri localization, 1.5 × 1 × 0.8 cm in size, which, in immunohistochemical staining, was evaluated as a neuroendocrine tumor. Also, Metastasis was observed. Conclusion. The rarest type of carcinoid tumor is ampullary located carcinoid tumor, and tumor size is not a reliable indicator for tumor aggressivity in ampullary carcinoid tumors.

  20. Skeletal metastasis of carcinoid tumors: Two case reports and review of the literature.

    PubMed

    Hori, Takeshi; Yasuda, Taketoshi; Suzuki, Kayo; Kanamori, Masahiko; Kimura, Tomoatsu

    2012-05-01

    Carcinoid tumors are neuroendocrine neoplasms derived from enterochromaffin cells. Skeletal metastases from carcinoid tumors are considered to be extremely rare. In this study, we present two cases of carcinoid tumors that metastasized to the bone. Furthermore, we review 50 published case reports and reveal the features of skeletal metastasis of carcinoid tumors. The first case involved a 59-year-old man with a history of multiple metastases of a lung carcinoid tumor. The patient complained of back pain and numbness in the lower limbs. Magnetic resonance imaging revealed metastases in the thoracic spine. A spinal decompression was performed and the symptoms were resolved. The second case involved a 74-year-old man had been diagnosed with a lung carcinoid tumor 15 years previously and complained of left thigh pain. A radiograph showed osteolytic lesions in the shaft of the left femur. We repaired the femur using an intramedullary nail following curettage of the tumor. A radiograph of the femur revealed a callus on the pathological fracture. The patient was able to walk using a crutch 3 months after surgery. We reviewed 50 cases that described skeletal metastasis from carcinoid tumors. The average age of the patients was 54.9 years and 33 patients (66%) were male. The most common site of skeletal metastasis was the spine. We also investigated the survival rate of patients who developed skeletal metastasis from carcinoid tumors. The findings showed that survival of patients who developed osteolytic skeletal metastasis was worse than that of patients who developed osteosclerotic skeletal metastasis.

  1. Proliferating trichilemmal tumor of the nose*

    PubMed Central

    Rosmaninho, Aristóteles; Caetano, Mónica; Oliveira, Ana; de Almeida, Teresa Pinto; Selores, Manuela; Alves, Rosário

    2012-01-01

    Proliferating trichilemmal tumor is a rare tumor originating in the external root sheath, that is usually found in the scalp of middle-aged or elderly females. Its histologic appearance may not correlate with its clinical behavior. In addition, there are no guidelines available for the treatment of these tumors, making its management a challenge for physicians. We report the case of a 53 year-old woman with a proliferating trichilemmal tumor on her nose, which is a very uncommon location for these lesions. PMID:23197215

  2. How Are Wilms Tumors Diagnosed?

    MedlinePlus

    ... Tumor Early Detection, Diagnosis, and Staging How Are Wilms Tumors Diagnosed? Wilms tumors are usually found when a ... Your Child’s Doctor About Wilms Tumor? More In Wilms Tumor About Wilms Tumor Causes, Risk Factors, and Prevention ...

  3. 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

  4. 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…

  5. 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.

  6. 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

  7. 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

  8. Metastatic carcinoid tumor--atypical presentation.

    PubMed

    Pleşa, Alina; Sarca, Emanuela; Maxim, Roxana

    2014-01-01

    Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating in the enterochromaffin cells and secreting mainly serotonin. Neuroendocrine tumors (NETs) are found throughout the intestinal tract, the appendix and terminal ileum being the most common locations, and are classified by site of origin and by degree of differentiation, with well-differentiated lesions representing those tumors formerly referred to as carcinoid tumors. The clinical symptoms are characterized by flushing, diarrhea, abdominal pain, and/or bronchial constriction and occur almost exclusively in patients with liver metastases due to the release of bioactive peptides and amines directly into the systemic circulation. We report the clinical, serological and histological diagnosis of a 67-years-old male patient with congestive heart failure secondary to carcinoid heart disease in the context of liver metastases of an ileum carcinoid tumor.

  9. Incidence of orbital, conjunctival and lacrimal gland malignant tumors in USA from Surveillance, Epidemiology and End Results, 1973-2009

    PubMed Central

    Hassan, Waleed M.; Bakry, Mohamed S.; Hassan, Housam M.; Alfaar, Ahmad S.

    2016-01-01

    AIM To determine the types and incidence of tumors affecting the orbit, conjunctiva and lacrimal glands and to study the trend line of these tumors in the United States from 1973 to 2009. METHODS We used the publicly available Surveillance, Epidemiology and End Results (SEER) database registries to determine the incidence rates. Age was adjusted to the 2000 US Standard Population. Patients were stratified according to age group, gender, race and histological grouping of tumor lesions. Three age groups were defined: 0-19, 20-49 and ≥50y. Annual percentage changes were calculated to examine trends. RESULTS The overall age adjusted incidence rate was 3.39 (95%CI: 3.27-3.52) per million person-years. The tumors were more prevalent in age group ≥50 counting 9.51 (95%CI: 9.11-9.92) per million person-years. Most of the soft tissue sarcomas occurred in the young age with incidence rate of 0.35 (95%CI: 0.28-0.42) per million person-years. Lymphomas were the dominant subtype in the adult population with incidence rate of 5.74 (95%CI: 5.43-6.06) per million person-years. Incidence rates were higher in males than females with an overall rate ratio of 1.31 (95%CI: 1.21-1.41) mainly caused by the increase in carcinoma subtypes. White race had a higher tumor incidence with a rate ratio of 1.47(95%CI: 1.25-1.73) driven by the higher incidence of most histological subtypes. Orbital tumors showed a higher incidence rate followed by conjunctival and lacrimal gland tumors with incidence rates of 1.59, 1.37 and 0.43 per million person-years respectively. The trend line of overall incidence of tumors showed a significant increase (APC=3.11, 95%CI: 2.61-3.61) mainly due to increase of lymphomas. This increase was higher than the increase of lymphomas at other sites. CONCLUSION Orbital, conjunctival and lacrimal gland malignant tumors differ among children and adults. Over the years there has been a noticeable increase in incidence rates of orbital and lacrimal gland tumors mainly

  10. Malignant phyllodes tumor of the breast: a case study.

    PubMed

    Keim-Malpass, Jessica; Mills, Anne M; Showalter, Shayna L

    2014-10-01

    Malignant phyllodes tumors of the breast are rare, fast-growing tumors that can be difficult to diagnose. A case study is featured about a young adult patient who lacked insurance and received a delayed diagnosis of malignant phyllodes tumor of the breast. This article includes pertinent clinical and age-specific considerations for comprehensive management.

  11. Brain Tumors (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old 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 ...

  12. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... Pediatric Brain Tumor Foundation Board Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  13. 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 ...

  14. 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. ...

  15. Neuroendocrine Tumor: Statistics

    MedlinePlus

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on how many people survive this type of ...

  16. 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

  17. 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 ...

  18. Hand and Wrist Tumors

    MedlinePlus

    ... Guide Journal of Hand Surgery (JHS) Home Anatomy Hand Tumors and Wrist Tumors Email to a friend * ... are seen commonly. CAUSES Common Types of Wrist Hand Tumors Ganglion Cysts (Figure 1): This is the ...

  19. Brain Tumors (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Brain Tumors KidsHealth > For Parents > Brain Tumors A A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  20. Lung Carcinoid Tumor: Surgery

    MedlinePlus

    ... Tumor Treating Lung Carcinoid Tumors Surgery to Treat Lung Carcinoid Tumors Surgery is the main treatment for ... often be cured by surgery alone. Types of lung surgery Different operations can be used to treat ( ...

  1. 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.

  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. 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.

  4. 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.

  5. Bone Transport for Reconstruction in Benign Bone Tumors

    PubMed Central

    Oh, Chang Seon; Cho, Yong Jin; Ahn, Yeong Seub; Na, Bo Ram

    2015-01-01

    Background The aim of this study was to assess the results of using the Ilizarov apparatus to transport bones in the treatment of benign bone tumors. Methods Seven patients (six males and one female) with benign bone tumors were treated by bone transport with an Ilizarov apparatus at our institution. Their mean age at surgery was 14.4 years (range, 4.8 to 36.9 years). The histological diagnoses were osteofibrous dysplasia (4), giant-cell tumor (1), intraosseous cavernous hemangioma (1), and aneurysmal bone cyst (1). Three radiological indices were used for evaluating the results: an external fixation index, a distraction index, and a maturation index. The bone and functional results were evaluated according to the Association for the Study and Application of the Method of Ilizarov classification. Results Five patients had bone union at the reconstructed site, one patient had a local recurrence, and the other had a nonunion at the docking site. The mean length of distraction was 7.3 cm (range, 5.1 to 12.1 cm). The mean external fixation index was 26.0 day/cm (range, 19.8 to 32.5 day/cm), the distraction index was 9.6 day/cm (range, 6.8 to 12.0 day/cm), and the maturation index was 14.9 day/cm (range, 8.0 to 22.5 day/cm). Ultimately, the bone and the functional results were rated excellent in six cases and good in one case. Conclusions Bone transport using the Ilizarov apparatus is a good treatment option in patients with bone defects after the resection of an active or aggressive benign bone tumor. PMID:26217473

  6. 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.

  7. Novel Homozygous Mutation of the Internal Translation Initiation Start Site of VHL is Exclusively Associated with Erythrocytosis: Indications for Distinct Functional Roles of von Hippel-Lindau Tumor Suppressor Isoforms.

    PubMed

    Bartels, Marije; van der Zalm, Marieke M; van Oirschot, Brigitte A; Lee, Frank S; Giles, Rachel H; Kruip, Marieke J H A; Gitz-Francois, Jerney J J M; Van Solinge, Wouter W; Bierings, Marc; van Wijk, Richard

    2015-11-01

    Congenital secondary erythrocytosis is a rare disorder characterized by increased red blood cell production. An important cause involves defects in the oxygen sensing pathway, in particular the PHD2-VHL-HIF axis. Mutations in VHL are also associated with the von Hippel-Lindau tumor predisposition syndrome. The differences in phenotypic expression of VHL mutations are poorly understood. We report on three patients with erythrocytosis, from two unrelated families. All patients show exceptionally high erythropoietin (EPO) levels, and are homozygous for a novel missense mutation in VHL: c.162G>C p.(Met54Ile). The c.162G>C mutation is the most upstream homozygous VHL mutation described so far in patients with erythrocytosis. It abolishes the internal translational start codon, which directs expression of VHLp19, resulting in the production of only VHLp30. The exceptionally high EPO levels and the absence of VHL-associated tumors in the patients suggest that VHLp19 has a role for regulating EPO levels that VHLp30 does not have, whereas VHLp30 is really the tumor suppressor isoform.

  8. 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.

  9. Endobronchial solitary fibrous tumor

    PubMed Central

    de Moraes, Marcelo Padovani Toledo; Colby, Thomas; Oliveira, Gilmar Felisberto; Hasimoto, Erica Nishida; Cataneo, Daniele Cristina; Cataneo, Antônio José Maria; De Faveri, Julio

    2016-01-01

    Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that appears primarily in the pleura and rarely in intrapulmonary or endobronchial topography. The authors report the case of a 47-year-old woman who presented obstructive respiratory symptoms for 4 years. The chest computed tomography and bronchoscopy showed an obstructive polypoid lesion located between the trachea and the left main bronchus associated with distal atelectasis of the left lung. A resection of the lesion was performed and, macroscopically, the mass was oval, encapsulated, and firm, measuring 2.3 × 1.7 × 1.5 cm. Histology revealed low-grade mesenchymal spindle cell neoplasm, with alternating cellularity, myxoid areas, and mature adipose tissue outbreaks, as well as blood vessels with irregular walls. The immunohistochemical study was positive for CD34, CD99, and BCL2. The diagnosis was SFT in an unusual topography. The patient’s symptoms remitted after tumor excision, and no systemic problems were evident. SFTs primarily affect adults and often follow a benign course; however, their behavior is unpredictable. The presence of necrosis and mitotic activity may portend a poor prognosis. Endobronchial SFTs are rare but should be evaluated and monitored similar to SFTs at other sites, with a long-term follow-up. PMID:28210572

  10. 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

  11. 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

    2015-12-04

    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.

  12. Evaluation of the effects of methotrexate released from polymeric implants in solid Ehrlich tumor.

    PubMed

    de Fátima Pereira, Adriana; Mara da Costa, Vivian; Cristina Magalhães Santos, Millene; Maciel de A Ribeiro, Rosy Iara; Gabriela Silva, Ana; Carmo Horta Pinto, Flávia; Vieira Teixeira Vidigal, Paula; Rodrigues Da Silva, Gisele

    2014-04-01

    In this study, the effects of the controlled and sustained release of methotrexate from poly(ɛ-caprolactone) implants were evaluated in the solid Ehrlich tumor. The drug locally leached from the implantable devices was capable of reducing the tumor growth and the necrotic areas of the tumor site. Furthermore, the methotrexate exerted its anti-tumor effect probably by the recruitment of neutrophils at the tumor site, which assisted in modulating the growth of the tumor. The polymeric implants containing methotrexate could be a chemotherapic alternative to treat locally solid tumors with lower systemic side effects.

  13. Max Wilms and his tumor.

    PubMed

    Raffensperger, John

    2015-02-01

    The most common cancer of the kidney in infants and children is named for Max Wilms, a German surgeon. How did this eponym come about? There were excellent reviews of this lesion before Wilms, a second year surgical assistant, published "Die Mischgeschwulste Der Niere" or The Mixed Tumors of the Kidney in 1899. At thirty two years of age, he demonstrated a masterful knowledge of pathology and embryology. Wilms' career was cut short when he became septic after operating on a prisoner of war during WWI. The survival rate for children with Wilms tumor was dismal until William Ladd, at the Boston Children's hospital introduced rational surgical treatment. By mid century, Robert Gross achieved a 47% survival rate with surgery combined with postoperative radiation. Sydney Farber treated Wilms tumors with Actinomycin-d and opened the door to cancer chemotherapy. With protocols developed by the National Wilms Tumor Study Group, the survival rate of children with Wilms tumors reached 90% by the end of the twentieth century.

  14. 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

  15. Gestational age

    MedlinePlus

    Fetal age - gestational age; Gestation; Neonatal gestational age; Newborn gestational age ... Gestational age can be determined before or after birth. Before birth, your health care provider will use ultrasound to ...

  16. Aging Skin

    MedlinePlus

    ... email address Submit Home > Healthy Aging > Wellness Healthy Aging Aging skin More information on aging skin When it ... treated early. Return to top More information on Aging skin Read more from womenshealth.gov Varicose Veins ...

  17. Epidemiology of Brain Tumors.

    PubMed

    McNeill, Katharine A

    2016-11-01

    Brain tumors are the commonest solid tumor in children, leading to significant cancer-related mortality. Several hereditary syndromes associated with brain tumors are nonfamilial. Ionizing radiation is a well-recognized risk factor for brain tumors. Several industrial exposures have been evaluated for a causal association with brain tumor formation but the results are inconclusive. A casual association between the common mutagens of tobacco, alcohol, or dietary factors has not yet been established. There is no clear evidence that the incidence of brain tumors has changed over time. This article presents the descriptive epidemiology of the commonest brain tumors of children and adults.

  18. Quality of Life Following Endoscopic Resection of Skull Base Tumors

    PubMed Central

    Cavel, Oren; Abergel, Avraham; Margalit, Nevo; Fliss, Dan M.; Gil, Ziv

    2012-01-01

    The objective of the study is to evaluate patients' quality of life (QOL) after endoscopic resection of skull base tumors. We estimated the QOL of 41 patients who underwent surgery for removal of skull base tumors via the expanded endonasal approach (EEA). The Anterior Skull Base Surgery Questionnaire (ASBS-Q), a multidimensional, disease-specific instrument containing 36 items was used. The rate of meningitis and cerebrospinal fluid leak was 1.4 and 0%, respectively. There was one case of uniocular visual impairment. The internal consistency of the instrument had a correlation coefficient (α-Cronbach score) of 0.8 to 0.92. Of 41 patients, 30 (75%) reported improvement or no change in overall QOL. Improved scores were reported in the physical function domain and worse scores in the specific symptoms domain. The most significant predictor of poor QOL was female gender, which led to a significant decrease in scores of all domains. Site of surgery, histology, age and comorbidity were not significant predictors of outcome. This paper further validates the use of the ASBS-Q for patients undergoing endoscopic skull base resection. The overall QOL of patients following endoscopic extirpation of skull base tumors is good. Female patients experience a significant decline in QOL compared with males. PMID:23542557

  19. [Nutrition, aging, old age].

    PubMed

    Iván, L

    1998-12-06

    In humans there is evidence that the restriction of total caloric intake appears to be more important than the restriction of any particular macronutrient. Today the mechanism of the effect of caloric restriction is unknown. With advancing age and the occurrence of concomitant illness there is an increased risk of developing nutritional deficiencies. Altered nutritional status is associated with the pathogenesis of a number of common diseases of the elderly, thus it would appear that nutritional modulation and manipulation represents one possible approach to successful aging and a healthy longevity. The conceptual framework of the paper suggests the need of a newer light of the aging processes namely by a holistic human-gero-ecological model and a personality oriented geriatry. There are accentuated the role of the nutrients and vitamins, the food intake and drug-nutrients interactions and the meanings of the differences between the normal and pathological aging.

  20. 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.

  1. Reconstruction of the natural history of metastatic cancer and assessment of the effects of surgery: Gompertzian growth of the primary tumor.

    PubMed

    Hanin, Leonid; Bunimovich-Mendrazitsky, Svetlana

    2014-01-01

    This work deals with retrospective reconstruction of the individual natural history of solid cancer and assessment of the effects of treatment on metastatic progression. This is achieved through a mathematical model of cancer progression accounting for the growth of the primary tumor, shedding of metastases, their dormancy and growth at secondary sites. To describe dynamics of the primary tumor, we used the Gompertz law, a parsimonious model of tumor growth accounting for its saturation. Parameters of the model were estimated from the age and volume of the primary tumor at surgery and volumes of detectable bone metastases collected from one breast cancer patient and one prostate cancer patient. This allowed us to estimate, for each patient, the ages at cancer onset and inception of all detected metastases, the expected metastasis latency time, parameters of the Gompertzian growth of the primary tumor, and the rates of growth of metastases before and after surgery. We found that for both patients: (1) onset of metastasis occurred when primary tumor was undetectable; (2) inception of all surveyed metastases except one occurred before surgery; and most importantly, (3) resection of the primary tumor led to a dramatic increase in the rate of growth of metastases. The model provides an excellent fit to the observed volumes of bone metastases in both patients. Our results agree well with those obtained previously based on exponential growth of the primary tumor, which serves as model validation. Our findings support the notion of metastatic dormancy and indirectly confirm the existence of stem-like cancer cells in breast and prostate tumors. We also explored the logistic law of primary tumor growth; however, it degenerated into the exponential law for both patients analyzed. The conclusions of this work are supported by a vast body of experimental, clinical and epidemiological knowledge accumulated over the last century.

  2. 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

  3. 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

  4. 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

  5. New approach to optical imaging of tumors

    NASA Astrophysics Data System (ADS)

    Achilefu, Samuel I.; Bugaj, Joseph E.; Dorshow, Richard B.; Jimenez, Hermo N.; Rajagopalan, Raghavan

    2001-07-01

    Site specific delivery of drugs and contrast agents to tumors protects normal tissues from the cytotoxic effect of drugs, and enhances the contrast between normal and diseased tissues. In optical medicine, biocompatible dyes can be used as phototherapeutics or as contrast agents. Previous studies have shown that the use of covalent or non-covalent dye conjugates of carriers such as antibiodies, liposomes, and polysaccharides improves the delivery of such molecules to tumors. However, large biomolecules can elicit adverse immunogenic reactions and also result in long blood clearance times, delaying visualization of target tissues. A viable alternative to this strategy is to use small bioactive molecule-dye conjugates. These molecules have several advantages over large biomolecules, including ease of synthesis of a variety of high purity compounds for combinatorial screening of new targets, enhanced diffusivity to solid tumors, and the ability to affect the pharmacokinetics of the conjugates by minor structural changes. Thus, we conjugated a near infrared absorbing dye to several bioactive peptides that specifically target overexpressed tumor receptors in established rat tumor lines. High tumor uptake of the conjugates was obtained without loss of either the peptide receptor affinity or the dye fluorescence. These findings demonstrate the efficacy of a small peptide-dye conjugate strategy for in vivo tumor imaging. Site-specific delivery of photodynamic therapy agents may also benefit from this approach.

  6. Innate Immune Cells Induce Hemorrhage in Tumors during Thrombocytopenia

    PubMed Central

    Ho-Tin-Noé, Benoit; Carbo, Carla; Demers, Mélanie; Cifuni, Stephen M.; Goerge, Tobias; Wagner, Denisa D.

    2009-01-01

    Platelets are crucial regulators of tumor vascular homeostasis and continuously prevent tumor hemorrhage through secretion of their granules. However, the reason for tumor bleeding in the absence of platelets remains unknown. Tumors are associated with inflammation, a cause of hemorrhage in thrombocytopenia. Here, we investigated the role of the inflamed tumor microenvironment in the induction of tumor vessel injury in thrombocytopenic mice. Using s.c. injections of vascular endothelial growth factor or tumor necrosis factor-α combined with depletion of neutrophils, we demonstrate that enhancing the opening of endothelial cell junctions was not sufficient to cause bleeding in the absence of platelets; instead, induction of tissue hemorrhage in thrombocytopenia required recruitment of leukocytes. Immunohistology revealed that thrombocytopenia-induced tumor hemorrhage occurs at sites of macrophage and neutrophil accumulation. Mice deficient in β2 or β3 integrins, which have decreased neutrophil and/or macrophage infiltration in their tumor stroma, were protected from thrombocytopenia-induced tumor hemorrhage, indicating that, in the absence of platelets, stroma-infiltrating leukocytes induced tumor vessel injury. This injury was independent of reactive oxygen species generation and of complement activation, as suggested by the persistence of tumor hemorrhage in C3- and nicotinamide adenine dinucleotide phosphate oxidase-deficient thrombocytopenic mice. Our results show that platelets counteract tumor-associated inflammation and that the absence of this platelet function elicits vascular injuries by tumor-infiltrating innate immune cells. PMID:19729481

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. The Fatty Acid Profile Analysis of Cyperus laxus Used for Phytoremediation of Soils from Aged Oil Spill-Impacted Sites Revealed That This Is a C18:3 Plant Species.

    PubMed

    Rivera Casado, Noemí Araceli; Montes Horcasitas, María del Carmen; Rodríguez Vázquez, Refugio; Esparza García, Fernando José; Pérez Vargas, Josefina; Ariza Castolo, Armando; Ferrera-Cerrato, Ronald; Gómez Guzmán, Octavio; Calva Calva, Graciano

    2015-01-01

    The effect of recalcitrant hydrocarbons on the fatty acid profile from leaf, basal corm, and roots of Cyperus laxus plants cultivated in greenhouse phytoremediation systems of soils from aged oil spill-impacted sites containing from 16 to 340 g/Kg total hydrocarbons (THC) was assessed to investigate if this is a C18:3 species and if the hydrocarbon removal during the phytoremediation process has a relationship with the fatty acid profile of this plant. The fatty acid profile was specific to each vegetative organ and was strongly affected by the hydrocarbons level in the impacted sites. Leaf extracts of plants from uncontaminated soil produced palmitic acid (C16), octadecanoic acid (C18:0), unsaturated oleic acids (C18:1-C18:3), and unsaturated eichosanoic (C20:2-C20:3) acids with a noticeable absence of the unsaturated hexadecatrienoic acid (C16:3); this finding demonstrates, for the first time, that C. laxus is a C18:3 plant. In plants from the phytoremediation systems, the total fatty acid contents in the leaf and the corm were negatively affected by the hydrocarbons presence; however, the effect was positive in root. Interestingly, under contaminated conditions, unusual fatty acids such as odd numbered carbons (C15, C17, C21, and C23) and uncommon unsaturated chains (C20:3n6 and C20:4) were produced together with a remarkable quantity of C22:2 and C24:0 chains in the corm and the leaf. These results demonstrate that weathered hydrocarbons may drastically affect the lipidic composition of C. laxus at the fatty acid level, suggesting that this species adjusts the cover lipid composition in its vegetative organs, mainly in roots, in response to the weathered hydrocarbon presence and uptake during the phytoremediation process.

  12. The Fatty Acid Profile Analysis of Cyperus laxus Used for Phytoremediation of Soils from Aged Oil Spill-Impacted Sites Revealed That This Is a C18:3 Plant Species

    PubMed Central

    Montes Horcasitas, María del Carmen; Rodríguez Vázquez, Refugio; Esparza García, Fernando José; Pérez Vargas, Josefina; Ariza Castolo, Armando; Ferrera-Cerrato, Ronald; Gómez Guzmán, Octavio

    2015-01-01

    The effect of recalcitrant hydrocarbons on the fatty acid profile from leaf, basal corm, and roots of Cyperus laxus plants cultivated in greenhouse phytoremediation systems of soils from aged oil spill-impacted sites containing from 16 to 340 g/Kg total hydrocarbons (THC) was assessed to investigate if this is a C18:3 species and if the hydrocarbon removal during the phytoremediation process has a relationship with the fatty acid profile of this plant. The fatty acid profile was specific to each vegetative organ and was strongly affected by the hydrocarbons level in the impacted sites. Leaf extracts of plants from uncontaminated soil produced palmitic acid (C16), octadecanoic acid (C18:0), unsaturated oleic acids (C18:1-C18:3), and unsaturated eichosanoic (C20:2-C20:3) acids with a noticeable absence of the unsaturated hexadecatrienoic acid (C16:3); this finding demonstrates, for the first time, that C. laxus is a C18:3 plant. In plants from the phytoremediation systems, the total fatty acid contents in the leaf and the corm were negatively affected by the hydrocarbons presence; however, the effect was positive in root. Interestingly, under contaminated conditions, unusual fatty acids such as odd numbered carbons (C15, C17, C21, and C23) and uncommon unsaturated chains (C20:3n6 and C20:4) were produced together with a remarkable quantity of C22:2 and C24:0 chains in the corm and the leaf. These results demonstrate that weathered hydrocarbons may drastically affect the lipidic composition of C. laxus at the fatty acid level, suggesting that this species adjusts the cover lipid composition in its vegetative organs, mainly in roots, in response to the weathered hydrocarbon presence and uptake during the phytoremediation process. PMID:26473488

  13. Tumor macroenvironment and metabolism.

    PubMed

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described.

  14. Genomic profiling of multiple sequentially acquired tumor metastatic sites from an “exceptional responder” lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response

    PubMed Central

    Biswas, Romi; Gao, Shaojian; Cultraro, Constance M.; Maity, Tapan K.; Venugopalan, Abhilash; Abdullaev, Zied; Shaytan, Alexey K.; Carter, Corey A.; Thomas, Anish; Rajan, Arun; Song, Young; Pitts, Stephanie; Chen, Kevin; Bass, Sara; Boland, Joseph; Hanada, Ken-Ichi; Chen, Jinqiu; Meltzer, Paul S.; Panchenko, Anna R.; Yang, James C.; Pack, Svetlana; Giaccone, Giuseppe; Schrump, David S.; Khan, Javed; Guha, Udayan

    2016-01-01

    We used next-generation sequencing to identify somatic alterations in multiple metastatic sites from an “exceptional responder” lung adenocarcinoma patient during his 7-yr course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ∼1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies showed increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy because of L869R mutation and increased migration because of ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a subclone metastasized early from the primary site and evolved independently in lymph nodes. PMID:27900369

  15. Conditional inactivation of the mouse Wwox tumor suppressor gene recapitulates the null phenotype†

    PubMed Central

    Abdeen, Suhaib K.; Mare, Sara Del; Hussain, Sadeeq; Remaileh, Muhannad Abu; Salah, Zaidoun; Hagan, John; Rawahneh, Maysoon; Pu, Xin-an; Russell, Stacey; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.; Aqeilan, Rami I.

    2013-01-01

    WW domain-containing oxidoreductase (WWOX) is highly conserved in both humans and murine. WWOX spans the second most common human chromosomal fragile site, FRA16D, and is commonly inactivated in multiple human cancers. Modeling WWOX inactivation in mice revealed a complex phenotype including postnatal lethality, defects in bone metabolism and steroidogenesis and tumor suppressor function resulting in osteosarcomas. For better understanding of WWOX roles in different tissues at distinct stages of development and in pathological conditions, Wwox conditional knockout mice were generated in which loxp sites flank exon 1 in the Wwox allele. We demonstrated that Cre-mediated recombination using EIIA-Cre, a Cre line expressed in germline, results in postnatal lethality by age of three weeks and decreased bone mineralization resembling total ablation of WWOX as in conventional null mice. This animal model will be useful to study distinct roles of WWOX in multiple tissues at different ages. PMID:23254685

  16. Conditional inactivation of the mouse Wwox tumor suppressor gene recapitulates the null phenotype.

    PubMed

    Abdeen, Suhaib K; Del Mare, Sara; Hussain, Sadeeq; Abu-Remaileh, Muhannad; Salah, Zaidoun; Hagan, John; Rawahneh, Maysoon; Pu, Xin-An; Russell, Stacey; Stein, Janet L; Stein, Gary S; Lian, Jane B; Aqeilan, Rami I

    2013-07-01

    WW domain-containing oxidoreductase (WWOX) is highly conserved in both human and murine. WWOX spans the second most common human chromosomal fragile site, FRA16D, and is commonly inactivated in multiple human cancers. Modeling WWOX inactivation in mice revealed a complex phenotype including postnatal lethality, defects in bone metabolism and steroidogenesis and tumor suppressor function resulting in osteosarcomas. For better understanding of WWOX roles in different tissues at distinct stages of development and in pathological conditions, Wwox conditional knockout mice were generated in which loxp sites flank exon 1 in the Wwox allele. We demonstrated that Cre-mediated recombination using EIIA-Cre, a Cre line expressed in germline, results in postnatal lethality by age of 3 weeks and decreased bone mineralization resembling total ablation of WWOX as in conventional null mice. This animal model will be useful to study distinct roles of WWOX in multiple tissues at different ages.

  17. Posterior Fossa Tumors.

    PubMed

    Brandão, Lara A; Young Poussaint, Tina

    2017-02-01

    Pediatric brain tumors are the leading cause of death from solid tumors in childhood. The most common posterior fossa tumors in children are medulloblastoma, atypical teratoid/rhabdoid tumor, cerebellar pilocytic astrocytoma, ependymoma, and brainstem glioma. Location, and imaging findings on computed tomography (CT) and conventional MR (cMR) imaging may provide important clues to the most likely diagnosis. Moreover, information obtained from advanced MR imaging techniques increase diagnostic confidence and help distinguish between different histologic tumor types. Here we discuss the most common posterior fossa tumors in children, including typical imaging findings on CT, cMR imaging, and advanced MR imaging studies.

  18. Superficial Fibromatosis Mimicking Glomus Tumor of the Second Toe

    PubMed Central

    Jo, Hyang Jeong; Kim, Gang Deuk; Kim, Yeung Jin; Choi, Deok Hwa; Park, Jae In

    2015-01-01

    Various types of tumor can occur in the subungual space, including glomus tumors, subungual exostosis, hemangioma, epidermal cysts, and malignant tumors. While fibromatosis can occur at various sites throughout the body, it is very rarely seen in the toe. Here, we are the first to report a case of superficial fibromatosis mimicking a glomus tumor in the subungual space of the second toe. The presentation of this condition shows the possibility of encountering uncommon superficial fibromatosis in the distal phalanx of the toe, and suggests that superficial fibromatosis should be included in the differential diagnosis of a glomus tumor in the toe. PMID:26330970

  19. Effect of tumor microenvironmental factors on tumor growth dynamics modeled by correlated colored noises with colored cross-correlation

    NASA Astrophysics Data System (ADS)

    Idris, Ibrahim Mu'awiyya; Abu Bakar, Mohd Rizam

    2016-07-01

    The effect of non-immunogenic tumor microenvironmental factors on tumor growth dynamics modeled by correlated additive and multiplicative colored noises is investigated. Using the Novikov theorem, Fox approach and Ansatz of Hanggi, an approximate Fokker-Planck equation for the system is obtained and analytic expression for the steady state distribution Pst(x) is derived. Based on the numerical results, we find that fluctuations of microenvironmental factors within the tumor site with parameter θ have a diffusive effect on the tumor growth dynamics, and the tumor response to the microenvironmental factors with parameter α inhibits growth at weak correlation time τ. Moreover, at increasing correlation time τ the inhibitive effect of tumor response α is suppressed and instead a systematic growth promotion is noticed. The result also reveals that the strength of the correlation time τ has a strong influence on the growth effects exerted by the non-immunogenic component of tumor microenvironment on tumor growth.

  20. 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 periphery in patients <5.6 months, in the inferotemporal quadrant of the posterior pole in patients 5.6-8.8 months, in the inferonasal quadrant in patients 8.8-13.2 months, and in the nasal and superotemporal periphery in patients >13.2 months. The distribution of MRI-invisible tumors was consistent with the asymmetry of mapped tumors. Conclusions MRI-based mapping revealed a previously unrecognized pattern of retinoblastoma localization that evolves with age at diagnosis. The structured spatiotemporal distribution of tumors may provide valuable clues about cellular or molecular events associated with tumorigenesis in the developing retina. PMID:26230335