Pediatric brain tumors of neuroepithelial tissue

International Nuclear Information System (INIS)

Papanagiotou, P.; Politi, M.; Bergmann, M.; Pekrun, A.; Juergens, K.U.

2014-01-01

Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [de

Tissue engineered tumor models.

Science.gov (United States)

Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

2010-08-01

Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

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Tozeren Aydin

2006-11-01

Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

Effect of brain- and tumor-derived connective tissue growth factor on glioma invasion.

Science.gov (United States)

Edwards, Lincoln A; Woolard, Kevin; Son, Myung Jin; Li, Aiguo; Lee, Jeongwu; Ene, Chibawanye; Mantey, Samuel A; Maric, Dragan; Song, Hua; Belova, Galina; Jensen, Robert T; Zhang, Wei; Fine, Howard A

2011-08-03

Tumor cell invasion is the principal cause of treatment failure and death among patients with malignant gliomas. Connective tissue growth factor (CTGF) has been previously implicated in cancer metastasis and invasion in various tumors. We explored the mechanism of CTGF-mediated glioma cell infiltration and examined potential therapeutic targets. Highly infiltrative patient-derived glioma tumor-initiating or tumor stem cells (TIC/TSCs) were harvested and used to explore a CTGF-induced signal transduction pathway via luciferase reporter assays, chromatin immunoprecipitation (ChIP), real-time polymerase chain reaction, and immunoblotting. Treatment of TIC/TSCs with small-molecule inhibitors targeting integrin β1 (ITGB1) and the tyrosine kinase receptor type A (TrkA), and short hairpin RNAs targeting CTGF directly were used to reduce the levels of key protein components of CTGF-induced cancer infiltration. TIC/TSC infiltration was examined in real-time cell migration and invasion assays in vitro and by immunohistochemistry and in situ hybridization in TIC/TSC orthotopic xenograft mouse models (n = 30; six mice per group). All statistical tests were two-sided. Treatment of TIC/TSCs with CTGF resulted in CTGF binding to ITGB1-TrkA receptor complexes and nuclear factor kappa B (NF-κB) transcriptional activation as measured by luciferase reporter assays (mean relative luciferase activity, untreated vs CTGF(200 ng/mL): 0.53 vs 1.87, difference = 1.34, 95% confidence interval [CI] = 0.69 to 2, P < .001). NF-κB activation resulted in binding of ZEB-1 to the E-cadherin promoter as demonstrated by ChIP analysis with subsequent E-cadherin suppression (fold increase in ZEB-1 binding to the E-cadherin promoter region: untreated + ZEB-1 antibody vs CTGF(200 ng/mL) + ZEB-1 antibody: 1.5 vs 6.4, difference = 4.9, 95% CI = 4.8 to 5.0, P < .001). Immunohistochemistry and in situ hybridization revealed that TrkA is selectively expressed in the most infiltrative glioma cells in situ

Tumor and normal tissue responses to fractioned non-uniform dose delivery

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Kaellman, P; Aegren, A; Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

1996-08-01

The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, {gamma}, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters {alpha} and {beta}. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs.

Fractionation parameters for human tissues and tumors

International Nuclear Information System (INIS)

Thames, H.D.; Turesson, I.; Bogaert, W. van den

1989-01-01

Time-dose factors such as fractionation sensitivity (α/β) can sometimes be estimated from clinical data, when there is a wide variation in dose, fraction size, treatment time, etc. This report summarizes estimates of fractionation parameters derived from clinical results. Consistent with the animal data, α/β is higher for acutely responding than for late-responding normal tissues. While many human tumors seem to be characterized by high α/β values, there are exceptions (e.g. melanomas). Repair kinetics may be slower in human than in rodent skin and mucosa, but there are no hard and fast estimates of the repair halftime. Regeneration in head and neck tumors is equivalent to a daily dose of 1 Gy or less, while in the mucosa it is equivalent to approximately 1.8 Gy/day. (author)

Identification of formaldehyde-responsive genes by suppression subtractive hybridization

International Nuclear Information System (INIS)

Lee, Min-Ho; Kim, Young-Ae; Na, Tae-Young; Kim, Sung-Hye; Shin, Young Kee; Lee, Byung-Hoon; Shin, Ho-Sang; Lee, Mi-Ock

2008-01-01

Formaldehyde is frequently used in indoor household and occupational environments. Inhalation of formaldehyde invokes an inflammatory response, including a variety of allergic signs and symptoms. Therefore, formaldehyde has been considered as the most prevalent cause of sick building syndrome, which has become a major social problem, especially in developing urban areas. Further formaldehyde is classified as a genotoxicant in the respiratory tract of rats and humans. To better understand the molecular mechanisms involved in formaldehyde intoxication, we sought differentially regulated genes by formaldehyde exposure to Hs 680.Tr human trachea cells, using polymerase chain reaction (PCR)-based suppression subtractive hybridization. We identified 27 different formaldehyde-inducible genes, including those coding for the major histocompatibility complex, class IA, calcyclin, glutathione S-transferase pi, mouse double minute 2 (MDM2), platelet-derived growth factor receptor alpha, and which are known to be associated with cell proliferation and differentiation, immunity and inflammation, and detoxification. Induction of these genes by formaldehyde treatment was confirmed by reverse transcription PCR and western blot analysis. Further, the expression of calcyclin, glutathione S-transferase pi, PDGFRA and MDM2 were significantly induced in the tracheal epithelium of Sprague Dawley rats after formaldehyde inhalation. Our results suggest that the elevated levels of these genes may be associated with the formaldehyde-induced toxicity, and that they deserve evaluation as potential biomarkers for formaldehyde intoxication

Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase

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Irina Kuznetsova

2017-12-01

Full Text Available Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA, which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site. We chose this cleavage site because elastase is expressed in the tumor microenvironment. Moreover, the exchange of the cleavage site previously has been shown to attenuate viral growth in lungs. Newly generated elastase-activated influenza viruses (AE viruses grew to similar titers in tumor cells as the trypsin-activated counterparts (AT viruses. Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors in mice reduced tumor growth similar to AT viruses and had a better therapeutic effect in heterologous human PANC-1-derived tumors. Therefore, the introduction of the attenuation marker “elastase cleavage site” in viral HA allows for safe, effective oncolytic virus therapy.

Tumor Engineering: The Other Face of Tissue Engineering

Energy Technology Data Exchange (ETDEWEB)

Ghajar, Cyrus M; Bissell, Mina J

2010-03-09

cancer, the training grounds have largely consisted of small rodents, despite marked differences between human and mouse physiology, or plastic dishes, even though just like our tissues and organs most tumors exist within three-dimensional proteinacious milieus. One could argue that this is comparable to training for a desert war in the arctic. In this special issue of tissue engineering, Fischbach-Teschl and colleagues build a strong case for engineering complex cultures analogous to normal organs to tractably model aspects of the human tumor microenvironment that simply cannot be reproduced with traditional two-dimensional cell culture techniques and that cannot be studied in a controlled fashion in vivo. This idea has gained considerable traction of late as concepts presented and convincingly shown years ago have only now begun to be appreciated. Perhaps, then, it is time to organize those who wish to build complex tumor models to study cancer biology under a common umbrella. Accordingly, we propose that tumor engineering be defined as the construction of complex culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. Inherent in this definition is the collaboration that must occur between physical and life scientists to guide the design of patterning techniques, materials, and imaging modalities for the study of cancer from the subcellular to tissue level in physiologically relevant contexts. To date, the most successful tissue engineering approaches have employed methods that recapitulate the composition, architecture, and/or chemical presentation of native tissue. For instance, induction of blood vessel growth for therapeutic purposes has been achieved with sequential release of vascular endothelial growth factor (VEGF) and platelet derived growth factor to induce and stabilize blood vessels. This approach imitates that which occurs during physiological

In vivo distribution of Mn-hematoporphyrin derivative in tumor bearing mice54

International Nuclear Information System (INIS)

Crone Escanye, M.C.; Anghilleri, L.T.; Robert, J.

1988-01-01

This paper presents results of preliminary studies of the in vivo uptake and biodistribution of manganese labbelled hematoporphyrin derivative (HpD). The results indicate that: (1) Mn-HpD 54 is crhomatographically very similar to HpD; (2) the tissue distribution of Mn-HpD 54 are overal compareble to that reported by other. Authors for C 14 -HpD and H 3 -HpD in tumor bearing mice. It seems therefore that maanganese labelled HpD for the non invasivequantitation of HpD concetration in tumor and normal tissues and may be hepful in assessing the potential usefulness of Mn-HpD in NMR imaging of living animals

NMR imaging of soft tissue tumors

International Nuclear Information System (INIS)

Laval-Jeantet, M.; Tobolsk, F.; Delepine, N.; Delepine, G.; Roger, B.; Cabanis, E.A.

1986-01-01

Preliminary findings on NMR imaging of 30 soft tissue tumors demonstrated the indispensable value of this examination (particularly when a surface antenna is used) for preoperative investigation and diagnosis of tumoral recurrence when compared with other radiologic techniques. The possible potential of NMR imaging for characterization of tissues, apart from lipoma or liposarcoma, cannot be evaluated at the present time [fr

Electroroentgenography in diagnosis of soft tissue tumors

International Nuclear Information System (INIS)

Vintergal'ter, S.F.; Vishevnik, B.I.

1989-01-01

Clinical, electroroentgenographic and X-ray studies of soft tissues were carried out in 425 patients with malignant (75), benign (246) soft tissue tumors and in cases of such soft tissue pathologies of the extremities and body (104). The paper discusses the technicalities of electroroentgenography which produces on one roentgenogram separate images of all components of soft tissues and bones in a given segment. A comparions of image quality assured by electroroentgeno- and roentgenography did not establish any significant difference in soft tissue tumor semiotics

Tumor tissue slice cultures as a platform for analyzing tissue-penetration and biological activities of nanoparticles.

Science.gov (United States)

Merz, Lea; Höbel, Sabrina; Kallendrusch, Sonja; Ewe, Alexander; Bechmann, Ingo; Franke, Heike; Merz, Felicitas; Aigner, Achim

2017-03-01

The success of therapeutic nanoparticles depends, among others, on their ability to penetrate a tissue for actually reaching the target cells, and their efficient cellular uptake in the context of intact tissue and stroma. Various nanoparticle modifications have been implemented for altering physicochemical and biological properties. Their analysis, however, so far mainly relies on cell culture experiments which only poorly reflect the in vivo situation, or is based on in vivo experiments that are often complicated by whole-body pharmacokinetics and are rather tedious especially when analyzing larger nanoparticle sets. For the more precise analysis of nanoparticle properties at their desired site of action, efficient ex vivo systems closely mimicking in vivo tissue properties are needed. In this paper, we describe the setup of organotypic tumor tissue slice cultures for the analysis of tissue-penetrating properties and biological activities of nanoparticles. As a model system, we employ 350μm thick slice cultures from different tumor xenograft tissues, and analyze modified or non-modified polyethylenimine (PEI) complexes as well as their lipopolyplex derivatives for siRNA delivery. The described conditions for tissue slice preparation and culture ensure excellent tissue preservation for at least 14days, thus allowing for prolonged experimentation and analysis. When using fluorescently labeled siRNA for complex visualization, fluorescence microscopy of cryo-sectioned tissue slices reveals different degrees of nanoparticle tissue penetration, dependent on their surface charge. More importantly, the determination of siRNA-mediated knockdown efficacies of an endogenous target gene, the oncogenic survival factor Survivin, reveals the possibility to accurately assess biological nanoparticle activities in situ, i.e. in living cells in their original environment. Taken together, we establish tumor (xenograft) tissue slices for the accurate and facile ex vivo assessment of

Affinity of 167Tm-citrate for tumor and liver tissue

International Nuclear Information System (INIS)

Ando, A.; Ando, I.; Hiraki, T.

1983-01-01

Strong affinity of 167 Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with 167 Tm-citrate because of its strong tumor affinity and because of the suitable physical characteristics of 167 Tm. A large amount of 167 Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. 167 Tm was not seen in necrotic tumor tissue. It was concluded that lysosomes did not play a major role in the tumor concentration of 167 Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumed that lysosomes played a considerably important role in the tumor concentration of 167 Tm, hepatoma AH109A possessing some residual features of the liver. 167 Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which 167 Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate). (orig.)

Gene expression patterns in pancreatic tumors, cells and tissues.

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Anson W Lowe

2007-03-01

Full Text Available Cancers of the pancreas originate from both the endocrine and exocrine elements of the organ, and represent a major cause of cancer-related death. This study provides a comprehensive assessment of gene expression for pancreatic tumors, the normal pancreas, and nonneoplastic pancreatic disease.DNA microarrays were used to assess the gene expression for surgically derived pancreatic adenocarcinomas, islet cell tumors, and mesenchymal tumors. The addition of normal pancreata, isolated islets, isolated pancreatic ducts, and pancreatic adenocarcinoma cell lines enhanced subsequent analysis by increasing the diversity in gene expression profiles obtained. Exocrine, endocrine, and mesenchymal tumors displayed unique gene expression profiles. Similarities in gene expression support the pancreatic duct as the origin of adenocarcinomas. In addition, genes highly expressed in other cancers and associated with specific signal transduction pathways were also found in pancreatic tumors.The scope of the present work was enhanced by the inclusion of publicly available datasets that encompass a wide spectrum of human tissues and enabled the identification of candidate genes that may serve diagnostic and therapeutic goals.

Tumor Imaging in Patients with Advanced Tumors Using a New 99mTc-Radiolabeled Vitamin B12 Derivative

DEFF Research Database (Denmark)

Sah, Bert-Ram; Schibli, Roger; Waibel, Robert

2014-01-01

Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin......, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells. In this prospective study, we investigated cancer-specific uptake of (99m)Tc-PAMA-cobalamin in 10 patients...... with various metastatic tumors. METHODS: Ten patients with biopsy-proven metastatic cancer were included. Dynamic imaging was started immediately after injection of 300-500 MBq of (99m)Tc-PAMA-cobalamin, and whole-body scintigrams were obtained at 10, 30, 60, 120, and 240 min and after 24 h. The relative tumor...

Modeling formalin fixation and histological processing with ribonuclease A: effects of ethanol dehydration on reversal of formaldehyde cross-links.

Science.gov (United States)

Fowler, Carol B; O'Leary, Timothy J; Mason, Jeffrey T

2008-07-01

Understanding the chemistry of protein modification by formaldehyde fixation and subsequent tissue processing is central to developing improved methods for antigen retrieval in immunohistochemistry and for recovering proteins from formalin-fixed, paraffin-embedded (FFPE) tissues for proteomic analysis. Our initial studies of single proteins, such as bovine pancreatic ribonuclease A (RNase A), in 10% buffered formalin solution revealed that upon removal of excess formaldehyde, monomeric RNase A exhibiting normal immunoreactivity could be recovered by heating at 60 degrees C for 30 min at pH 4. We next studied tissue surrogates, which are gelatin-like plugs of fixed proteins that have sufficient physical integrity to be processed using normal tissue histology. Following histological processing, proteins could be extracted from the tissue surrogates by combining heat, detergent, and a protein denaturant. However, gel electrophoresis revealed that the surrogate extracts contained a mixture of monomeric and multimeric proteins. This suggested that during the subsequent steps of tissue processing protein-formaldehyde adducts undergo further modifications that are not observed in aqueous proteins. As a first step toward understanding these additional modifications we have performed a comparative evaluation of RNase A following fixation in buffered formaldehyde alone and after subsequent dehydration in 100% ethanol by combining gel electrophoresis, chemical modification, and circular dichroism spectroscopic studies. Our results reveal that ethanol-induced rearrangement of the conformation of fixed RNase A leads to protein aggregation through the formation of large geometrically compatible hydrophobic beta-sheets that are likely stabilized by formaldehyde cross-links, hydrogen bonds, and van der Waals interactions. It requires substantial energy to reverse the formaldehyde cross-links within these sheets and regenerate protein monomers free of formaldehyde modifications

Low temperature synthesis of no-carrier-added [{sup 11}C]formaldehyde with metal hydrides and preparation of [1-{sup 11}C]1,2,3,4-Tetrahydro-{beta}-Carboline Derivatives

Energy Technology Data Exchange (ETDEWEB)

Nader, M.W.; Zeisler, S.K.; Theobald, A.; Oberdorfer, F

1998-12-01

A comparative study has been performed on the selective reduction of cyclotron-produced [{sup 11}C]carbon dioxide to [{sup 11}C]formaldehyde with solutions of various complex metal hydrides at temperatures between -52 and +25 deg. C. Under optimal reaction conditions, lithium tetrahydridoaluminate gave the highest yield of [{sup 11}C]formaldehyde (58%, decay-corrected), followed by lithium triethylhydridoborate (34%) and sodium tetrahydridoborate (22%). Radiochemically pure [{sup 11}C]formaldehyde could be obtained with lithium tetrahydridoaluminate and sodium tetrahydridoborate, but not with lithium triethyl hydridoborate. The produced [{sup 11}C]formaldehyde was used for the synthesis of [1-{sup 11}C]1,2,3,4-tetrahydro-{beta}-carboline derivatives by the Pictet-Spengler reaction.

T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor

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Kim Tae-Sik

2011-06-01

Full Text Available Abstract Background Although the graft-versus-tumor (GVT effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB transplantation have not been well studied. Methods We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells. Results We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays. Conclusions Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.

Ultrasonographic findings of benign soft tissue tumors

International Nuclear Information System (INIS)

Kim, Ki Sung; Oh, Dong Heon; Jung, Tae Gun; Kim, Yong Kil; Kwon, Jung Hyeok

1994-01-01

To clarify the characteristic sonographic features of benign soft tissue tumors and to evaluate the usefulness of sonographic imaging. We retrospectively reviewed ultrasonographic images of 70 cases in 68 patients with histologically proved benign soft tissue tumors. The tumors include 33 lipomas, 11 hemangiomas, 11 lymphangiomas, 7 neurilemmomas, 4 epidermoid cysts, 2 fibromas, 1 mesenchymoma, and 1 myxoma. The sonographic appearances of the lesions were mainly solid in 53 cases(33 lipomas, 8 hemangiomas, 2 lymphangiomas, 7 neurilemmomas, 2 fibromas and 1 mesenchymoma), mainly cystic in 14 cases(1 hemangioma, 8 lymphangiomas, 4 epidermoid cysts, and 1 myxomal), and mixed in 3 cases(2 hemangiomas and 1 lymphangioma). Although an accurate histologic prediction could not be made in most cases, certain patterns appeared to be characteristic of specific tumor types. 26 cases(78%) of lipoma were seen as lentiform, iso- or hyperechoic, solid mass. Hemangioma had variable appearance and characteristic calcifications were seen in 3 cases. Unicameral or multiseptated cystic mass with variable thickness of echogenic septa and solid portion was the characteristic finding of lymhangioma. Neurilemmoma showed lobulated, oval to round , relatively hypoechoic mass or with without internal cystic portion. Sonographic evaluation of benign soft tissue tumors is useful in demonstrating the location, size, extent, and internal characteristic of the mass. A relatively confident diagnosis can made when the characteristic features of the benign soft tissue tumor are present on sonographic imaging

Ultrasonographic findings of benign soft tissue tumors

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Kim, Ki Sung; Oh, Dong Heon; Jung, Tae Gun; Kim, Yong Kil; Kwon, Jung Hyeok [Dongkang Genernal Hospital, Ulsan (Korea, Republic of)

1994-05-15

To clarify the characteristic sonographic features of benign soft tissue tumors and to evaluate the usefulness of sonographic imaging. We retrospectively reviewed ultrasonographic images of 70 cases in 68 patients with histologically proved benign soft tissue tumors. The tumors include 33 lipomas, 11 hemangiomas, 11 lymphangiomas, 7 neurilemmomas, 4 epidermoid cysts, 2 fibromas, 1 mesenchymoma, and 1 myxoma. The sonographic appearances of the lesions were mainly solid in 53 cases(33 lipomas, 8 hemangiomas, 2 lymphangiomas, 7 neurilemmomas, 2 fibromas and 1 mesenchymoma), mainly cystic in 14 cases(1 hemangioma, 8 lymphangiomas, 4 epidermoid cysts, and 1 myxomal), and mixed in 3 cases(2 hemangiomas and 1 lymphangioma). Although an accurate histologic prediction could not be made in most cases, certain patterns appeared to be characteristic of specific tumor types. 26 cases(78%) of lipoma were seen as lentiform, iso- or hyperechoic, solid mass. Hemangioma had variable appearance and characteristic calcifications were seen in 3 cases. Unicameral or multiseptated cystic mass with variable thickness of echogenic septa and solid portion was the characteristic finding of lymhangioma. Neurilemmoma showed lobulated, oval to round , relatively hypoechoic mass or with without internal cystic portion. Sonographic evaluation of benign soft tissue tumors is useful in demonstrating the location, size, extent, and internal characteristic of the mass. A relatively confident diagnosis can made when the characteristic features of the benign soft tissue tumor are present on sonographic imaging.

Characterization of Soft Tissue Tumors by Diffusion-Weighted Imaging

International Nuclear Information System (INIS)

Pekcevik, Yeliz; Kahya, Mehmet Onur; Kaya, Ahmet

2015-01-01

Diffusion-weighted imaging (DWI) is a noninvasive method for investigation of tumor histological content. It has been applied for some musculoskeletal tumors and reported to be useful. The aim of the present study was to prospectively evaluate the apparent diffusion coefficient (ADC) values of benign and malignant soft tissue tumors and to determine if ADC can help differentiate these tumors. DWI was performed on 25 histologically proven soft tissue masses. It was obtained with a single-shot echo-planar imaging technique using a 1.5T magnetic resonance (MR) machine. The mean ADC values were calculated. We grouped soft tissue tumors as benign cystic, benign solid or mixed, malignant cystic and malignant solid or mixed tumors and compared mean ADC values between these groups. There was only one patient with a malignant cystic tumor and was not included in the statistical analysis. The median ADC values of benign and malignant tumors were 2.31 ± 1.29 and 0.90 ± 0.70 (median ± interquartile range), respectively. The mean ADC values were different between benign and malignant tumors (P = 0.031). Benign cystic tumors had significantly higher ADC values than benign solid or mixed tumors and malignant solid or mixed tumors (p values were < 0.001 and 0.003, respectively). Malignant solid or mixed tumors had lower ADC values than benign solid or mixed tumors (P = 0.02). Our preliminary results have shown that although there is some overlap between benign and malignant tumors, adding DWI, MR imaging to routine soft tissue tumor protocols may improve diagnostic accuracy

Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

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Erickson-Miller Connie L

2012-09-01

Full Text Available Abstract Background Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Methods Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR, and for TPO-R protein expression by immunohistochemistry (IHC. Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. Results MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43% and malignant (3-17% breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Conclusions Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and

Extravascular transport in normal and tumor tissues.

Science.gov (United States)

Jain, R K; Gerlowski, L E

1986-01-01

The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

Affinity of /sup 167/Tm-citrate for tumor and liver tissue

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Ando, A; Ando, I; Hiraki, T; Sakamoto, K; Hisada, K; Takeshita, M

1983-10-07

Strong affinity of /sup 167/Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with /sup 167/Tm-citrate because of its strong tumor affinity and because of the suitable physical characteristics of /sup 167/Tm. A large amount of /sup 167/Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. /sup 167/Tm was not seen in necrotic tumor tissue. It was concluded that lysosomes did not play a major role in the tumor concentration of /sup 167/Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumed that lysosomes played a considerably important role in the tumor concentration of /sup 167/Tm, hepatoma AH109A possessing some residual features of the liver. /sup 167/Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which /sup 167/Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate).

Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models.

Science.gov (United States)

Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Miyake, Kentaro; Miyake, Masuyo; Singh, Arun S; Eckardt, Mark A; Nelson, Scott D; Russell, Tara A; Dry, Sarah M; Li, Yunfeng; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Singh, Shree Ram; Eilber, Fritz C; Hoffman, Robert M

2018-03-18

Undifferentiated soft tissue sarcoma (USTS) is a recalcitrant and heterogeneous subgroup of soft tissue sarcoma with high risk of metastasis and recurrence. Due to heterogeneity of USTS, there is no reliably effective first-line therapy. We have generated tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R), which previously showed strong efficacy on single patient-derived orthotopic xenograft (PDOX) models of Ewing's sarcoma and follicular dendritic cell sarcoma. In the present study, tumor resected from 4 patients with a biopsy-proven USTS (2 undifferentiated pleomorphic sarcoma [UPS], 1 undifferentiated sarcoma not otherwise specified [NOS] and 1 undifferentiated spindle cell sarcoma [USS]) were grown orthotopically in the biceps femoris muscle of mice to establish PDOX models. One USS model and one UPS model were doxorubicin (DOX) resistant. One UPS and the NOS model were partially sensitive to DOX. DOX is first-line therapy for these diseases. S. typhimurium A1-R arrested tumor growth all 4 models. In addition to arresting tumor growth in each case, S. typhimurium A1-R was significantly more efficacious than DOX in each case, thereby surpassing first-line therapy. These results suggest that S. typhimurium A1-R can be a general therapeutic for USTS and possibly sarcoma in general. Published by Elsevier Inc.

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues

International Nuclear Information System (INIS)

Cifola, Ingrid; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A

2011-01-01

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models

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Wu Xianhua

2012-08-01

Full Text Available Abstract Background Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models. Methods PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC tissues into immunodeficient (SCID/nude mice. HER-2 gene copy number (GCN and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group. Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient’s ESCC tissues. Similarity between the PDECX models and their corresponding patient’s ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation. Results None of the PDECX models (or their corresponding patient’s ESCC tissues harbored HER-2 gene amplification. IHC staining showed HER-2 positivity (IHC 2+ in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+. A second HER-2 positive (IHC 2+ model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model. Conclusions

Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.

Science.gov (United States)

Cho, Yong Beom; Hong, Hye Kyung; Choi, Yoon-La; Oh, Ensel; Joo, Kyeung Min; Jin, Juyoun; Nam, Do-Hyun; Ko, Young-Hyeh; Lee, Woo Yong

2014-04-01

Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples. Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts. From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor. Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice.

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Song, Lin; Zhou, Xin; Jia, Hong-Jun; Du, Mei; Zhang, Jin-Ling; Li, Liang

2016-08-01

To study the effect of hGC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. hGC-MSCs group were given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, mRNA expression of proliferation, invasion, EMT-related molecules were determined. 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of hGC-MSCs group were significantly higher than those of PBS group and the more the number of hGC-MSCs, the higher the tumor tissue volume; mRNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of hGC-MSCs group were higher than those of PBS group, and mRNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. hGC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Exposure to formaldehyde: a challenge of occupational health significance

International Nuclear Information System (INIS)

Kaonga, K.

2009-01-01

The use of formaldehyde as the fixative for general microscopic demonstration of tissues in medical laboratory establishments is as significant as the diagnosis of the underlying ailment. Instantaneous human exposure to formaldehyde elicits symptoms that may include watery eyes, headache, inflamed throat and dyspnea. The gaseous chemical is toxic, allergenic and carcinogenic. A study to determine the incidence of human exposure to formaldehyde was carried out at the University Teaching Hospital in Lusaka, Zambia from January to December, 2007. Anonymous questionnaires on various aspects of human exposure to formaldehyde were given to laboratory technical personnel. Exposure to formaldehyde was determined using general consideration model comprising points awarded to participants according to their responses. Five points represented the maximum level of exposure, while one point denoted the minimum encounter. There were 8 incidents of formaldehyde pollution, with five being emissions from 210-litre formalin receptacles whose stoppers were inadvertently left loose overnight, while three involved accidental breakage of Winchester bottles of formalin. A total of 115 people were exposed during the year. Fifteen (13.0 percent) participants scored one point each, while 20 (17.4 percent) participants obtained 2 points each. Thirty-five (30.4 percent) participants got 3 points each, while 30 (26.0 percent) participants received 4 points each. Twenty-five (21.7 percent) participants attained 5 points each. Human exposure to formaldehyde is an issue of occupational health concern. Participants with a score of 3 points or more need regular medical check ups in order to safeguard their health. Programs on effective management of hazardous chemicals are worth setting up.(author)

Formaldehyde in the Galactic Centre

International Nuclear Information System (INIS)

Cohen, R.J.; Few, R.W.

1981-01-01

Formaldehyde 6-cm absorption in the direction of the Galactic Centre has been surveyed using the Jodrell Bank MK II radio telescope (beam-width 10 x 9 arcmin). The observations sample the region - 2 0 = 0 and - 0 0 .5 = 0 .5, with a velocity range of 620 km s -1 , a velocity resolution of 2.1 km s -1 and an rms noise level of approximately 0.03 K. The data are presented as contour maps showing line temperature as a function of latitude and velocity (b-V maps) and as a function of longitude and velocity (l-V maps). Similar maps of the line-to-continuum ratio are also presented. The radial distribution of formaldehyde (H 2 CO) in the Galactic Centre region is derived using two different kinematic models which give similar results. Formaldehyde is strongly concentrated in the Galactic Centre in a layer of latitude extent approximately 0 0 .5 and longitude extent approximately 4 0 which contains one quarter of all the H 2 CO in the Galaxy. The distribution is centred on l approximately 1 0 . The individual H 2 CO features are described in detail. (author)

BMI-1 targeting interferes with patient-derived tumor-initiating cell survival and tumor growth in prostate cancer

Science.gov (United States)

Yusuff, Shamila; Davis, Stephani; Flaherty, Kathleen; Huselid, Eric; Patrizii, Michele; Jones, Daniel; Cao, Liangxian; Sydorenko, Nadiya; Moon, Young-Choon; Zhong, Hua; Medina, Daniel J.; Kerrigan, John; Stein, Mark N.; Kim, Isaac Y.; Davis, Thomas W.; DiPaola, Robert S.; Bertino, Joseph R.; Sabaawy, Hatem E.

2016-01-01

Purpose Current prostate cancer (PCa) management calls for identifying novel and more effective therapies. Self-renewing tumor-initiating cells (TICs) hold intrinsic therapy-resistance and account for tumor relapse and progression. As BMI-1 regulates stem cell self-renewal, impairing BMI-1 function for TICs-tailored therapies appears to be a promising approach. Experimental design We have previously developed a combined immunophenotypic and time-of-adherence assay to identify CD49bhiCD29hiCD44hi cells as human prostate TICs. We utilized this assay with patient derived prostate cancer cells and xenograft models to characterize the effects of pharmacological inhibitors of BMI-1. Results We demonstrate that in cell lines and patient-derived TICs, BMI-1 expression is upregulated and associated with stem cell-like traits. From a screened library, we identified a number of post-transcriptional small molecules that target BMI-1 in prostate TICs. Pharmacological inhibition of BMI-1 in patient-derived cells significantly decreased colony formation in vitro and attenuated tumor initiation in vivo, thereby functionally diminishing the frequency of TICs, particularly in cells resistant to proliferation- and androgen receptor (AR)-directed therapies, without toxic effects on normal tissues. Conclusions Our data offer a paradigm for targeting TICs and support the development of BMI-1-targeting therapy for a more effective PCa treatment. PMID:27307599

78 FR 44090 - Formaldehyde; Third-Party Certification Framework for the Formaldehyde Standards for Composite...

Science.gov (United States)

2013-07-23

... Formaldehyde; Third-Party Certification Framework for the Formaldehyde Standards for Composite Wood Products..., concerning a third-party certification framework for the formaldehyde standards for composite wood products... Environmental protection, Composite wood products, Formaldehyde, Reporting and recordkeeping, Third-party...

Histology-specific therapy for advanced soft tissue sarcoma and benign connective tissue tumors.

Science.gov (United States)

Silk, Ann W; Schuetze, Scott M

2012-09-01

Molecularly targeted agents have shown activity in soft tissue sarcoma (STS) and benign connective tissue tumors over the past ten years, but response rates differ by histologic subtype. The field of molecularly targeted agents in sarcoma is increasingly complex. Often, clinicians must rely on phase II data or even case series due to the rarity of these diseases. In subtypes with a clear role of specific factors in the pathophysiology of disease, such as giant cell tumor of the bone and diffuse-type tenosynovial giant cell tumor, it is reasonable to treat with newer targeted therapies, when available, in place of chemotherapy when systemic treatment is needed to control disease. In diseases without documented implication of a pathway in disease pathogenesis (e.g. soft tissue sarcoma and vascular endothelial growth factor), clear benefit from drug treatment should be established in randomized phase III trials before implementation into routine clinical practice. Histologic subtype will continue to emerge as a critical factor in treatment selection as we learn more about the molecular drivers of tumor growth and survival in different subtypes. Many of the drugs that have been recently developed affect tumor growth more than survival, therefore progression-free survival may be a more clinically relevant intermediate endpoint than objective response rate using Response Evaluation Criteria In Solid Tumors (RECIST) in early phase sarcoma trials. Because of the rarity of disease and increasing need for multidisciplinary management, patients with connective tissue tumors should be evaluated at a center with expertise in these diseases. Participation in clinical trials, when available, is highly encouraged.

201Tl scintigraphic evaluation of tumor mass and viability of bone and soft-tissue tumors

International Nuclear Information System (INIS)

Tsuda, Takatoshi; Kubota, Masahiro; Yoshida, Satoru; Shibata, Masahito; Wakabayashi, Jun-ichi; Obata, Hiroyuki; Matsuyama, Toshikatsu; Usui, Masamichi; Ishii, Sei-ichi.

1994-01-01

To characterize 201 Tl uptake in patients with bone and soft-tissue tumor, we studied 49 patients with surgically proven tumors and one patient with a tumor diagnosed arteriographically. In 37 of our 50 patients, the tumor was evaluated with 201 Tl and arteriography. Moreover, in 14 of patients with pre-operative chemotherapy, pathologic changes were graded on the basis of percent tumor necrosis as defined histologically. The percent tumor necrosis histologically was compared with changes in the scintigraphic and conventional angiographic studies. Radiologic comparisons demonstrated a high degree of correlation with images of 201 Tl and both arterial and blood pool phase of 99m Tc-HMDP. Ninety-six percent of 28 malignant tumors had positive 201 Tl uptake. None of the patients showed any thallium accumulation in the soft tissues or skeleton adjacent to the lesion. Activity of 201 Tl was mainly dependent upon a tumor blood flow and a vascular density. In of 14 cases with the preoperative chemotherapeutic treatment, 201 Tl scintigraphic changes showed concordance with % tumor necrosis. Thallium-201 was superior to 99m Tc-HMDP in predicting tumor response to chemotherapy. Interestingly, delayed images of 99m Tc-HMDP of 5 responders with >90% tumor necrosis showed decreased uptake in the adjacent bone to the tumor mass lesions. It seems to be quite all right to consider that a major determinant of 201 Tl uptake is intratumoral angiogenecity, which is closely connected with tumor viability. Therefore, 201 Tl is a sensitive radiopharmaceutical for detection of vascular rich bone and soft-tissue tumors, and appears to be a simple and an accurate test for evaluating the response to specific therapeutic regimens of malignant bone and soft-tissue tumors. (author)

Effects of Sodium Selenite on Formaldehyde Induced Renal Toxicity in Mice

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Shabnam Mohammadi 1,2 * , Maryam Moghimian 3, Hanieh Torabzadeh 4, Mahla Langari 4, Roghayeh Nazeri 4, Zahra Karimi 4, Elham Sangari 4, Najmeh Jagarmi 5, Alireza Mohammad Zadeh 3, Mehdi Karimi 7, Kamyar Tavakkoli 8, Ali Delshad 9, Fatemeh Mohammadzadeh 3, Majid Ghayour-Mobarhan 10

2016-12-01

Full Text Available Background: Formaldehyde is widely used for industrial applications. Renal injury is an adverse effect associated with formaldehyde. Few studies have explored the potential benefits of protective factors on formaldehyde induced renal toxicity. This study evaluated the dose dependent effects of sodium selenite on the biochemical and histopathological effects of formaldehyde on murine kidney. Methods: Forty eight adult Balb/c male mice were randomized into six groups: a control group, a formaldehyde group and experimental III-VI groups. Formaldehyde group was injected with 10 mg/kg formaldehyde and groups III-VI received intraperitoneally doses of 0.1, 0.2, 0.4, 0.8 mg/kg selenium. After two weeks, a stereological study was done in accordance with the principle of Cavalieri and serum concentrations of urea and creatinine were measured. Data were analyzed using ANOVA and SPSS software. Results: Glomerosclerosis, necrosis and vacuolization were observed in the convoluted tubules of animals treated with formaldehyde. The biochemical markers, volume and count of glomeruli in the group treated with formaldehyde was significantly difference compared to the control group (P<0.05. The volume of the glomeruli in the group treated with 0.2 and 0.4 mg selenium and urea level in the group treated with 0.4 and 0.1 mg/kg selenium was significantly difference compared to the control group (P <0.05. The count of glomeruli and creatinine level in the selenium group was significantly difference compared to the control group (P ≤ 0.0001. Conclusions: A dose of 0.2 mg/kg of sodium selenite caused partial protective effect on the renal tissue and function in exposed to formaldehyde.

Chemical modification of conventional cancer radiotherapy. Tumor sensitization combined with normal tissue protection

International Nuclear Information System (INIS)

Kagiya, Tsutomu

2006-01-01

Nitrotriazole radiosensitizer, Sanazole (AK-2123, N-(2'-methoxyethyl)-2-(3''-nitro-1''-triazolyl) acetamide) developed by Kyoto University group was studied by 18 groups of 7 countries on fundamental aspects and clinical studies by 30 groups of 12 countries, and reported its effects on tumor sensitization of conventional cancer radiotherapy. On the other hand, the glucosides of vitamin C (Ascorbic acid glucoside, (AsAG) and water soluble derivative of vitamin-E (α-tocopherol glucoside, TMG) developed by Kyoto University group were studied fundamentally by 4 groups of 4 countries and clinically by 2 groups of 2 countries, and reported their effects on normal tissue protection in cancer treatments. These two studies of tumor sensitization and normal tissue protection were proposed as an advanced strategy of conventional cancer radiotherapy. (author)

Initial inventory of alternatives to biocidal products containing formaldehyde of formaldehyde releasers

NARCIS (Netherlands)

Wezenbeek JM; Janssen MPM; Scheepmaker JWA; MSP; M&V

2015-01-01

Formaldehyde is de werkzame stof in veel desinfecteer- en conserveringsmiddelen, maar deze stof is kankerverwekkend. Daarom zal formaldehyde naar verwachting per 1 januari 2016 op Europees niveau als zodanig worden geclassificeerd (carcinogeen 1B). Dit kan betekenen dat formaldehyde-houdende

Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors.

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Trancău, I O; Huică, R; Surcel, M; Munteanu, A; Ursaciuc, C

2015-01-01

EWS/FLI-1 fusion mainly appears in Ewing's sarcoma or the primitive neuroectodermal tumors and represents a genomic marker for these tumors. However, it can appear with lower frequency in other soft tissue tumors. The paper investigates the presence of EWS/FLI-1 fusion in clinically diagnosed sarcoma belonging to different non-Ewing connective tissue tumors in order to search for a possible new biomarker valuable for investigators. 20 patients with soft tissue tumors, who underwent surgery, were tested. Intra-operative samples of normal and tumor tissue were collected for histopathological diagnosis and genetics determinations. The patients' RNA from tumor and normal peritumoral tissue was extracted and EWS/FLI-1 fusion screened by quantitative real-time PCR. The relative expression of the fusion in the tumor sample was compared to the similar expression in normal tissue. The amplification in the threshold zone was shown by 5 samples (25%): 2 clear cell sarcoma, 1 fibrosarcoma, 1 malignant tumor of nerve sheath, 1 metastatic adenocarcinoma. We differentiated between the unspecific amplification and concluded that these are weak positive results. Genomic investigation may establish the tumor malignancy and its possible affiliation earlier than histopathology. It can support the screening of EWS/FLI-1 fusion in a larger variety of clinically diagnosed soft tissue tumors.

Tumor-derived Matrix Metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer

International Nuclear Information System (INIS)

Zhang, Bin; Niu, Yun; Niu, Ruifang; Sun, Baocun; Hao, Xishan; Cao, Xuchen; Liu, Yanxue; Cao, Wenfeng; Zhang, Fei; Zhang, Shiwu; Li, Hongtao; Ning, Liansheng; Fu, Li

2008-01-01

Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression. However, its relevance to the progression of human breast cancer is yet to be established. Furthermore, it is not clear whether MMP-13 can be used as an independent breast cancer biomarker. This study was conducted to assess the expression profile of MMP-13 protein in invasive breast carcinomas to determine its diagnostic and prognostic significance, as well as its correlation with other biomarkers including estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, MMP-2, MMP-9, tissue inhibitor of MMP-1 and -2 (TIMP-1 and TIMP-2). Immunohistochemistry (IHC) was performed on paraffin-embedded tissue microarray containing specimens from 263 breast carcinomas. The intensity and the extent of IHC were scored by pathologists in blind fashion. The correlation of the gene expression profiles with patients' clinicopathological features and clinical outcomes were analyzed for statistical significance. MMP-13 protein was detected in the cytoplasm of the malignant cells and the peritumoral stromal cells. MMP-13 expression by tumor cells (p < 0.001) and stromal fibroblasts (p <0.001) both correlated with carcinoma infiltration of lymph nodes. MMP-13 also correlated with the expression of Her-2/neu (p = 0.015) and TIMP-1 (p < 0.010), respectively in tumor cells. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes. Moreover, high levels of MMP-13 expression were associated with decreased overall survival. In parallel, the prognostic value of MMP-13 expressed by peritumoral fibroblasts seems less significant. Our data suggest that lymph node status, tumor size, Her-2/neu expression, TIMP-1 and MMP-13 expression in cancer cells are independent prognostic factors. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and inversely correlated with the

Tumor-Derived Exosomes and Their Role in Cancer Progression.

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Whiteside, Theresa L

2016-01-01

Tumor cells actively produce, release, and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis, and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as noninvasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation. © 2016 Elsevier Inc. All rights reserved.

Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression

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Viktor Fleming

2018-03-01

Full Text Available The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME, which inhibits antitumor immune responses, supporting the disease progression. Myeloid-derived suppressor cells (MDSC play a crucial role in this immunosuppressive TME. Those cells represent a heterogeneous population of immature myeloid cells with a strong immunosuppressive potential. They inhibit an antitumor reactivity of T cells and NK cells. Furthermore, they promote angiogenesis, establish pre-metastatic niches, and recruit other immunosuppressive cells such as regulatory T cells. Accumulating evidences demonstrated that the enrichment and activation of MDSC correlated with tumor progression, recurrence, and negative clinical outcome. In the last few years, various preclinical studies and clinical trials targeting MDSC showed promising results. In this review, we discuss different therapeutic approaches on MDSC targeting to overcome immunosuppressive TME and enhance the efficiency of current tumor immunotherapies.

Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer.

Science.gov (United States)

Gao, Jing; Wang, Haixing; Zang, Wanchun; Li, Beifang; Rao, Guanhua; Li, Lei; Yu, Yang; Li, Zhongwu; Dong, Bin; Lu, Zhihao; Jiang, Zhi; Shen, Lin

2017-09-01

Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor-2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA-based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

Science.gov (United States)

Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

2011-06-13

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

Treatment of oral soft tissues benign tumors using laser

Science.gov (United States)

Crisan, Bogdan; Baciut, Mihaela; Crisan, Liana; Bran, Simion; Rotar, Horatiu; Dinu, Cristian; Moldovan, Iuliu; Baciut, Grigore

2014-01-01

The present study aimed to assess the efficacy and indications of surgical laser therapy in the treatment of oral soft tissues benign tumors compared to classic surgery. A controlled clinical study was conducted in a group of 93 patients presenting various forms of oral soft tissues benign tumors. These patients were examined pre-and postoperatively and the oral benign tumors were measured linearly and photographed. The surgery of laser-assisted biopsy excision of oral benign tumors was carried out using a diode laser device of 980 nm. In patients who received surgical laser treatment, therapeutic doses of laser to biostimulate the operated area were administered on the first day after the surgery. The interventions of conventional excision of oral soft tissues benign tumors consisted in removing them using scalpel. In patients who have received therapeutic doses of laser for biostimulation of the operated area, a faster healing of wound surfaces and tumor bed was observed during the first days after surgery. Two weeks after the surgical treatment, good healing without scarring or discomfort in the area of excision was documented. Surgical treatment of oral soft tissues benign tumors with laser assisted postoperative therapy confirms the benefits of this surgical procedure. A faster healing process of the excision area due to laser biostimulation of low intensity has been observed in patients with surgical laser assisted treatment in the postoperative period.

Patient-Derived Antibody Targets Tumor Cells

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An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

β class II tubulin predominates in normal and tumor breast tissues

International Nuclear Information System (INIS)

Dozier, James H; Hiser, Laree; Davis, Jennifer A; Thomas, Nancy Stubbs; Tucci, Michelle A; Benghuzzi, Hamed A; Frankfurter, Anthony; Correia, John J; Lobert, Sharon

2003-01-01

Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs

Thallium-201 scintigraphy for bone and soft tissue tumors

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Tokuumi, Yuji; Tsuchiya, Hiroyuki; Sunayama, Chiaki; Matsuda, Eizo; Asada, Naohiro; Taki, Junichi; Sumiya, Hisashi; Miyauchi, Tsutomu; Tomita, Katsuro [Kanazawa Univ. (Japan). School of Medicine

1995-05-01

This study was undertaken to assess the usefulness of thallium-201 scintigraphy in bone and soft tissue tumors. Pre-therapy scintigraphy was undertaken in a total of 136 patients with histologically confirmed diagnosis, consisting of 74 with malignant bone and soft tissue tumors, 39 with benign ones, 12 with diseases analogous to tumors, and 11 others. Thallium activity was graded on a scale of 0-4: 0=background activity, 1=equivocal activity, 2=definitive activity, but less than myocardium, 3=definite activity equal to myocardium, and 4=activity greater than myocardium. In the group of malignant tumors, thallium-201 uptake was found in 80%, although it was low for chondrosarcoma (2/8) and malignant Schwannoma (one/3). The group of benign tumors, however, showed it in only 41%, being restricted to those with giant cell tumors, chondroblastoma, fibromatosis, and osteoid osteoma. Thallium-201 uptake was also found in all 8 patients with metastatic tumors. In 23 patients undergoing thallium imaging before and after chemotherapy, scintigraphic findings revealed a high correlation with histopathological findings. Thus, thallium-201 scintigraphy may be potentially used to distinguish malignant from benign bone and soft tissue tumors, except for a few histopathological cases, as well as to determine loco-regional metastases and response to chemotherapy. (N.K.).

Involvement of host stroma cells and tissue fibrosis in pancreatic tumor development in transgenic mice.

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Itai Spector

Full Text Available INTRODUCTION: Stroma cells and extracellular matrix (ECM components provide the pivotal microenvironment for tumor development. The study aimed to evaluate the importance of the pancreatic stroma for tumor development. METHODS: Pancreatic tumor cells were implanted subcutaneously into green fluorescent protein transgenic mice, and stroma cells invading the tumors were identified through immunohistochemistry. Inhibition of tumor invasion by stroma cells was achieved with halofuginone, an inhibitor of TGFβ/Smad3 signaling, alone or in combination with chemotherapy. The origin of tumor ECM was evaluated with species-specific collagen I antibodies and in situ hybridization of collagen α1(I gene. Pancreatic fibrosis was induced by cerulean injection and tumors by spleen injection of pancreatic tumor cells. RESULTS: Inhibition of stroma cell infiltration and reduction of tumor ECM levels by halofuginone inhibited development of tumors derived from mouse and human pancreatic cancer cells. Halofuginone reduced the number only of stroma myofibroblasts expressing both contractile and collagen biosynthesis markers. Both stroma myofibroblasts and tumor cells generated ECM that contributes to tumor growth. Combination of treatments that inhibit stroma cell infiltration, cause apoptosis of myofibroblasts and inhibit Smad3 phosphorylation, with chemotherapy that increases tumor-cell apoptosis without affecting Smad3 phosphorylation was more efficacious than either treatment alone. More tumors developed in fibrotic than in normal pancreas, and prevention of tissue fibrosis greatly reduced tumor development. CONCLUSIONS: The utmost importance of tissue fibrosis and of stroma cells for tumor development presents potential new therapy targets, suggesting combination therapy against stroma and neoplastic cells as a treatment of choice.

Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

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Dapkute D

2017-11-01

Full Text Available Dominyka Dapkute,1,2 Simona Steponkiene,1 Danute Bulotiene,1 Liga Saulite,3 Una Riekstina,3 Ricardas Rotomskis1,4 1Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 2Institute of Biosciences, Vilnius University, Vilnius, Lithuania; 3Faculty of Medicine, University of Latvia, Riga, Latvia; 4Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Vilnius, Lithuania Purpose: Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs.Materials and methods: Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used.Results: QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the

Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice

International Nuclear Information System (INIS)

Andres, A.C.; Schoenenberger, C.A.; Groner, B.; Henninghausen, L.; LeMeur, M.; Gelinger, P.

1987-01-01

The activated human Ha-ras oncogene was subjected to the control of the promoter region of the murine whey acidic protein (Wap) gene, which is expressed in mammary epithelial cells in response to lactogenic hormones. The Wap-ras gene was stably introduced into the mouse germ line of five transgenic mice (one male and four females). Wap-ras expression was observed in the mammary glands of lactating females in two lines derived from female founders. The tissue-directed and hormone-dependent Wap expression was conferred on the Ha-ras oncogene. The signals governing Wap expression are located within 2.5 kilobases of 5' flanking sequence. The other two lines derived from female founders did not express the chimeric gene. In the line derived from the male founder the Wap-ras gene is integrated into the Y chromosome. Expression was found in the salivary gland of male animals only. After a long latency, Wap-ras-expressing mice developed tumors. The tumors arose in tissues expressing Wap-ras - i.e., mammary or salivary glands. Compared to the corresponding nonmalignant tissues, Wap-ras expression was enhanced in the tumors

Estimation of formaldehyde concentration in working environment by using 14C-labeled formaldehyde

International Nuclear Information System (INIS)

Hamada, Masana; Kitano, Katsuhiro; Miketa, Daigo

2010-01-01

It became to be ruled to check the concentration of formaldehyde as the estimation of airborne concentration in working environment since March, 2009 and then, liquid chromatography and easily analyzing equipment methods, mainly gas detector tube method, are given as the official methods. When we estimate the airborne formaldehyde concentration in a work place where only formalin is used as a formaldehyde emission source such as a room for pathological examination, it is not necessary to separate formaldehyde and therefore not very reasonable to use liquid chromatography including troublesome procedures. On the other hand, gas detector tube method is convenient but has possibility of causing errors by individual differences. The errors might cause the additional differences of the control classes and of the measures to prevent workers from being exposed to harmful materials. In order to solve these problems and to exam alternative analyzing method for formaldehyde, we tried to measure the concentration by using 14 C-labelled one. After 14 C-labelled formaldehyde solution is put into the emission source of formaldehyde (formalin solution), the vaporized samples are taken by silica gel tubes quantitatively as usual at the estimation of airborne concentration in working environment. By counting the desorpted amount of radioactivity from silica gel, it was revealed that the obtained concentrations of formaldehyde are correspond to both the calculated values and the values indicated on the gas detector tubes at various concentrations. In this study, we used the amount below the lower activity limits of radioactive material. Except the users who have radioisotope controlled area, we are allowed to use 14 C-labeled materials below 10 MBq without being regulated under the Law Concerning Prevention of Radiation Hazards. When we use a little amount of 14 C-formaldehyde at formaldehyde using area to check the concentration of vaporized formaldehyde, this method was found to

Differential diagnosis between benign and malignant soft tissue tumors utilizing ultrasound parameters.

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Morii, Takeshi; Kishino, Tomonori; Shimamori, Naoko; Motohashi, Mitsue; Ohnishi, Hiroaki; Honya, Keita; Aoyagi, Takayuki; Tajima, Takashi; Ichimura, Shoichi

2018-01-01

Preoperative discrimination between benign and malignant soft tissue tumors is critical for the prevention of excess application of magnetic resonance imaging and biopsy as well as unplanned resection. Although ultrasound, including power Doppler imaging, is an easy, noninvasive, and cost-effective modality for screening soft tissue tumors, few studies have investigated reliable discrimination between benign and malignant soft tissue tumors. To establish a modality for discrimination between benign and malignant soft tissue tumors using ultrasound, we extracted the significant risk factors for malignancy based on ultrasound information from 40 malignant and 56 benign pathologically diagnosed soft tissue tumors and established a scoring system based on these risk factors. The maximum size, tumor margin, and vascularity evaluated using ultrasound were extracted as significant risk factors. Using the odds ratio from a multivariate regression model, a scoring system was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.85), confirming the accuracy of the scoring system. Ultrasound is a useful modality for establishing the differential diagnosis between benign and malignant soft tissue tumors.

Tumor-derived circulating endothelial cell clusters in colorectal cancer.

KAUST Repository

Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain B; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess H; Tai, Joyce A; Tan, Joanna H; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte; van Dam, Rob M; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y; Hillmer, Axel M; Tan, Min-Han

2016-01-01

Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

Tumor-derived circulating endothelial cell clusters in colorectal cancer.

KAUST Repository

Cima, Igor

2016-06-29

Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

Ultrasound of musculoskeletal soft-tissue tumors superficial to the investing fascia.

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Hung, Esther Hiu Yee; Griffith, James Francis; Ng, Alex Wing Hung; Lee, Ryan Ka Lok; Lau, Domily Ting Yi; Leung, Jason Chi Shun

2014-06-01

The objective of our study was to evaluate the diagnostic accuracy of ultrasound in assessing musculoskeletal soft-tissue tumors superficial to the investing fascia. Seven hundred fourteen superficial soft-tissue tumors evaluated with ultrasound by two musculoskeletal radiologists were retrospectively reviewed. In all ultrasound reports, the reporting radiologists provided one, two, or three diagnoses depending on their perceived level of diagnostic certainty. Two hundred forty-seven tumors had subsequent histologic correlation, thus allowing the accuracy of the ultrasound diagnosis to be determined. Images of the lesions with a discordant ultrasound diagnosis and histologic diagnosis were reviewed, and the ultrasound features were further classified as concordant with the known histologic diagnosis, concordant with the known histologic diagnosis with atypical features present, or discordant with the known histologic diagnosis. Four hundred sixty-seven tumors without pathologic confirmation were followed up clinically. Overall the accuracy of ultrasound examination for assessing superficial soft-tissue masses was 79.0% when all differential diagnoses were considered and 77.0% when only the first differential diagnosis was considered. The sensitivity and specificity of the first ultrasound diagnosis were 95.2% and 94.3%, respectively, for lipoma; 73.0% and 97.7% for vascular malformation; 80.0% and 95.4% for epidermoid cyst; and 68.8% and 95.2% for nerve sheath tumor. Reduced observer awareness of specific tumor entities tended to contribute to underdiagnosis more than poor specificity of ultrasound findings. Most tumors (236/247, 96%) were benign. The sensitivity and specificity of ultrasound for identifying malignant superficial soft-tissue tumors was 94.1% and 99.7%, respectively. The diagnostic accuracy of ultrasound in the assessment of superficial musculoskeletal soft-tissue tumors is high and can be improved through increased radiologist awareness of less

78 FR 34795 - Formaldehyde; Third-Party Certification Framework for the Formaldehyde Standards for Composite...

Science.gov (United States)

2013-06-10

... Formaldehyde; Third-Party Certification Framework for the Formaldehyde Standards for Composite Wood Products... Certification Framework for the Formaldehyde Standards for Composite Wood Products AGENCY: Environmental... certification, auditing and reporting of third-party certifiers, recordkeeping, enforcement, laminated products...

An Automatic Occlusion Device for Remote Control of Tumor Tissue Ischemia

Science.gov (United States)

El-Dahdah, Hamid; Wang, Bei; He, Guanglong; Xu, Ronald X.

2015-01-01

We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multi-modal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics. PMID:20082532

Helical 3D-CT images of soft tissue tumors in the hand

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Otani, Kazuhiro; Kikuchi, Hiraku; Tan, Akihiro; Hamanishi, Chiaki; Tanaka, Seisuke [Kinki Univ., Osaka-Sayama (Japan). School of Medicine

2000-02-01

X-ray, ultrasonograph CT, MRI and angiography are used to detect tumoral lesions. Recently, helical CT has been revealed to be a useful method for the diagnosis and preoperative evaluation of soft tissue tumors, by which high quality and accurate three dimensional (3D) images can be obtained quickly. We analyzed the preoperative 3D-CT images of soft tissue tumors in the hands of 11 cases (hemangioma in 6 cases, giant cell tumor, lipoma, angiofibroma, chondrosarcoma and malignant fibro-histiocytoma in one case each). Enhanced 3D-CT clearly visualized hemangiomas and solid tumors from the surrounding tissues. The tumors could easily be observed from any direction and color-coded according to the CT number. Helical 3D-CT was thus confirmed to be useful for the diagnosis and preoperative planning by indicating the details of tumor expansion into surrounding tissues. (author)

Acidosis and Formaldehyde Secretion as a Possible Pathway of Cancer Pain and Options for Improved Cancer Pain Control.

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Hoang, Ba X; Shaw, D Graeme; Han, Bo; Fang, Josephine Y; Nimni, Marcel

2015-09-01

The prevalence of cancer pain in patients with cancer is high. The majority of efforts are spent on research in cancer treatment, but only a small fraction focuses on cancer pain. Pain in cancer patients, viewed predominantly as a secondary issue, is considered to be due to the destruction of tissues, compression of the nerves, inflammation, and secretion of biological mediators from the necrotic tumor mass. As a result, opioid drugs have remained as the primary pharmacological therapy for cancer pain for the past hundred years. This report reviews evidence that cancer pain may be produced by the metabolic effects of two byproducts of cancer-high acidity in the cancer microenvironment and the secretion of formaldehyde and its metabolites. We propose the research and development of therapeutic approaches for preemptive, short- and long-term management of cancer pain using available drugs or nutraceutical agents that can suppress or neutralize lactic acid production in combination with formaldehyde scavengers. We believe this approach may not only improve cancer pain control but may also enhance the quality of life for patients.

78 FR 51696 - Formaldehyde; Third-Party Certification Framework for the Formaldehyde Standards for Composite...

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2013-08-21

... Formaldehyde; Third-Party Certification Framework for the Formaldehyde Standards for Composite Wood Products..., concerning a third-party certification framework for the formaldehyde standards for composite wood products... INFORMATION CONTACT. List of Subjects in 40 CFR Part 770 Environmental protection, Composite wood products...

Ultrasonic characterization of three animal mammary tumors from three-dimensional acoustic tissue models

Science.gov (United States)

Mamou, Jonathan M.

This dissertation investigated how three-dimensional (3D) tissue models can be used to improve ultrasonic tissue characterization (UTC) techniques. Anatomic sites in tissue responsible for ultrasonic scattering are unknown, which limits the potential applications of ultrasound for tumor diagnosis. Accurate 3D models of tumor tissues may help identify the scattering sites. Three mammary tumors were investigated: a rat fibroadenoma, a mouse carcinoma, and a mouse sarcoma. A 3D acoustic tissue model, termed 3D impedance map (3DZM), was carefully constructed from consecutive histologic sections for each tumor. Spectral estimates (scatterer size and acoustic concentration) were obtained from the 3DZMs and compared to the same estimates obtained with ultrasound. Scatterer size estimates for three tumors were found to be similar (within 10%). The 3DZMs were also used to extract tissue-specific scattering models. The scattering models were found to allow clear distinction between the three tumors. This distinction demonstrated that UTC techniques may be helpful for noninvasive clinical tumor diagnosis.

The margin of exposure to formaldehyde in alcoholic beverages.

Science.gov (United States)

Monakhova, Yulia B; Jendral, Julien A; Lachenmeier, Dirk W

2012-06-01

Formaldehyde has been classified as carcinogenic to humans (WHO IARC group 1). It causes leukaemia and nasopharyngeal cancer, and was described to regularly occur in alcoholic beverages. However, its risk associated with consumption of alcohol has not been systematically studied, so this study will provide the first risk assessment of formaldehyde for consumers of alcoholic beverages.Human dietary intake of formaldehyde via alcoholic beverages in the European Union was estimated based on WHO alcohol consumption data and literature on formaldehyde contents of different beverage groups (beer, wine, spirits, and unrecorded alcohol). The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMD) for 10 % effect obtained from dose-response modelling of animal experiments.For tumours in male rats, a BMD of 30 mg kg(-1) body weight per day and a "BMD lower confidence limit" (BMDL) of 23 mg kg(-1) d(-1) were calculated from available long-term animal experiments. The average human exposure to formaldehyde from alcoholic beverages was estimated at 8·10(-5) mg kg(-1) d(-1). Comparing the human exposure with BMDL, the resulting MOE was above 200,000 for average scenarios. Even in the worst-case scenarios, the MOE was never below 10,000, which is considered to be the threshold for public health concerns.The risk assessment shows that the cancer risk from formaldehyde to the alcohol-consuming population is negligible and the priority for risk management (e.g. to reduce the contamination) is very low. The major risk in alcoholic beverages derives from ethanol and acetaldehyde.

Ultrasound Shear Wave Simulation of Breast Tumor Using Nonlinear Tissue Elasticity

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Dae Woo Park

2016-01-01

Full Text Available Shear wave elasticity imaging (SWEI can assess the elasticity of tissues, but the shear modulus estimated in SWEI is often less sensitive to a subtle change of the stiffness that produces only small mechanical contrast to the background tissues. Because most soft tissues exhibit mechanical nonlinearity that differs in tissue types, mechanical contrast can be enhanced if the tissues are compressed. In this study, a finite element- (FE- based simulation was performed for a breast tissue model, which consists of a circular (D: 10 mm, hard tumor and surrounding tissue (soft. The SWEI was performed with 0% to 30% compression of the breast tissue model. The shear modulus of the tumor exhibited noticeably high nonlinearity compared to soft background tissue above 10% overall applied compression. As a result, the elastic modulus contrast of the tumor to the surrounding tissue was increased from 0.46 at 0% compression to 1.45 at 30% compression.

Ultrasound Shear Wave Simulation of Breast Tumor Using Nonlinear Tissue Elasticity.

Science.gov (United States)

Park, Dae Woo

2015-01-01

Shear wave elasticity imaging (SWEI) can assess the elasticity of tissues, but the shear modulus estimated in SWEI is often less sensitive to a subtle change of the stiffness that produces only small mechanical contrast to the background tissues. Because most soft tissues exhibit mechanical nonlinearity that differs in tissue types, mechanical contrast can be enhanced if the tissues are compressed. In this study, a finite element- (FE-) based simulation was performed for a breast tissue model, which consists of a circular (D: 10 mm, hard) tumor and surrounding tissue (soft). The SWEI was performed with 0% to 30% compression of the breast tissue model. The shear modulus of the tumor exhibited noticeably high nonlinearity compared to soft background tissue above 10% overall applied compression. As a result, the elastic modulus contrast of the tumor to the surrounding tissue was increased from 0.46 at 0% compression to 1.45 at 30% compression.

MRI findings of inflammatory myofibroblastic tumor of the soft tissue

International Nuclear Information System (INIS)

Deng Demao; Meng Quanfei; Chen Yinming; Zhou Chunxiang; Gao Zhenhua; Yang Zheng; Wang Liantang

2008-01-01

Objective: To describe MR findings in inflammatory myofibroblastic tumor (IMT) of the soft tissue. Methods: MR manifestations of 11 cases of IMT of the soft tissue were retrospectively analyzed, and the MR findings were correlated with surgical and histological results. Results: The pathological classification of the tumors was type I in 1 case, type II in 4 cases, mainly type II admixed with type I in 3 cases, and mainly type II admixed with type III in 3 eases. In 4 cases with primary tumor, the tumors were spheroid in shape, with well-defined margin and pseudocapsule. In 2 eases with primary axillary tumor and 5 cases with recurrent tumor, the tumors were irregular in shape, with ill-defined margin and invasion of adjacent structures. The tumors were mainly isointensive in T 1 -weighted images. Tumors of different pathological classifications had different signal intensities in T 2 -weighted images: 1 case of type I tumor was bright; 4 cases of type II tumor and 3 cases of type II tumor admixed with type I tumor were slightly bright; 3 cases of type II tumor admixed with type III were isointense or slightly hypointense in signal. All of the 11 cases in the study exhibited 'pitaya cross-section sign' in T 2 -weighted sequence, which referred to discrete punctuate foci of relatively hypointensity in the background of hyperintensity, slightly hypointensity or isointensity. All of the 11 cases exhibited inhomogeneously significant enhancement after gadolinium administration. In the follow-up of the 6 eases of primary tumor, 4 cases had recurrence, 1 case had no recurrence, and 1 case was lost in the follow-up process. In the follow-up of the 5 cases of recurrent tumor, 4 cases showed recurrence again, and 3 cases were lost in the follow-up process. Conclusions: The IMT of the soft tissue has characteristic MR features. The signal intensity of the tumor on T2-weighted sequence could reflect the pathological type of the tumor' to some extent. 'pitaya cross

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

Science.gov (United States)

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

2009-02-13

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

Soft Tissue Tumor Immunohistochemistry Update: Illustrative Examples of Diagnostic Pearls to Avoid Pitfalls.

Science.gov (United States)

Wei, Shi; Henderson-Jackson, Evita; Qian, Xiaohua; Bui, Marilyn M

2017-08-01

- Current 2013 World Health Organization classification of tumors of soft tissue arranges these tumors into 12 groups according to their histogenesis. Tumor behavior is classified as benign, intermediate (locally aggressive), intermediate (rarely metastasizing), and malignant. In our practice, a general approach to reaching a definitive diagnosis of soft tissue tumors is to first evaluate clinicoradiologic, histomorphologic, and cytomorphologic features of the tumor to generate some pertinent differential diagnoses. These include the potential line of histogenesis and whether the tumor is benign or malignant, and low or high grade. Although molecular/genetic testing is increasingly finding its applications in characterizing soft tissue tumors, currently immunohistochemistry still not only plays an indispensable role in defining tumor histogenesis, but also serves as a surrogate for underlining molecular/genetic alterations. Objective- To provide an overview focusing on the current concepts in the classification and diagnosis of soft tissue tumors, incorporating immunohistochemistry. This article uses examples to discuss how to use the traditional and new immunohistochemical markers for the diagnosis of soft tissue tumors. Practical diagnostic pearls, summary tables, and figures are used to show how to avoid diagnostic pitfalls. - Data were obtained from pertinent peer-reviewed English-language literature and the authors' first-hand experience as bone and soft tissue pathologists. - -The ultimate goal for a pathologist is to render a specific diagnosis that provides diagnostic, prognostic, and therapeutic information to guide patient care. Immunohistochemistry is integral to the diagnosis and management of soft tissue tumors.

Melamine-formaldehyde aerogels

Science.gov (United States)

Pekala, Richard Walter

1992-01-01

Organic aerogels that are transparent and essentially colorless are prepa from the aqueous, sol-gel polymerization of melamine with formaldehyde. The melamine-formaldehyde (MF) aerogels have low densities, high surface areas, continuous porsity, ultrafine cell/pore sizes, and optical clarity.

Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

International Nuclear Information System (INIS)

Hoshiba, Takashi; Tanaka, Masaru

2013-01-01

Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression

Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

Energy Technology Data Exchange (ETDEWEB)

Hoshiba, Takashi [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan); International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan); Tanaka, Masaru, E-mail: tanaka@yz.yamagata-u.ac.jp [Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 (Japan)

2013-09-20

Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

Characterization and Application of Urea-Formaldehyde-Furfural Co-condensed Resins as Wood Adhesives

Directory of Open Access Journals (Sweden)

Jizhi Zhang

2014-08-01

Full Text Available Furfural, as an organic compound derived from biomass materials, was used to partially substitute for formaldehyde in the synthesis of UF resin. Urea-formaldehyde-furfural co-condensed (UFFR resins with different substitute ratios of furfural to formaldehyde (FR/F were prepared. The effects of the FR/F substitute ratio on the performances of UFFR resins were investigated. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS and Fourier transform infrared spectroscopy (FT-IR were applied to characterize the chemical structures of UFFR resins. Plywood bonded by these resins was manufactured, and its bond strength and formaldehyde emission were measured. The results showed that the substitution of furfural in place of formaldehyde could reduce the free formaldehyde content effectively at the expense of prolongation of the curing time. The spectra of MALDI-TOF and FTIR confirmed the co-condensation of urea-formaldehyde-furfural both in uncured and cured resins. Plywood prepared under optimized parameters could yield high bond strength and low formaldehyde emission, which were 0.84 MPa and 0.23 ppm, respectively. The optimized parameters were as follows: a FR/F substitute ratio of 1/3; 1% (NH42S2O8 as the curing agent; and a hot pressing temperature of 130 °C. Hence, it is feasible to substitute partially formaldehyde by furfural to prepare UFFR resins as wood adhesives for plywood.

Formaldehyde in reusable protective gloves.

Science.gov (United States)

Pontén, Ann

2006-05-01

Due to the clinical findings in a single patient's case, formaldehyde was suspected to be present in clinically relevant levels in reusable protective gloves. Therefore, 9 types of gloves were investigated with the semi-quantitative chromotropic acid method. It was found that 6/9 gloves emitted some formaldehyde and that 4/9 gloves emitted > or =40 microg of formaldehyde. Most of the formaldehyde was found on the inside of the gloves. To get an indication of the clinical relevance, a comparison with a protective cream declared to contain the formaldehyde-releasing agent diazolidinyl urea was performed by comparing areas of gloves with areas of cream layers with thickness 1-2 mg/cm(2). It was found that the amounts of formaldehyde emitted from the gloves might be in the same range as emitted from a layer of cream.

Microradioimmunoassay for antibodies to tumor-associated antigens

International Nuclear Information System (INIS)

Huang, J.C.C.; Berczi, I.; Froese, G.; Tsay, H.M.; Sehon, A.H.

1975-01-01

A versatile microradioimmunoassay for the detection of antibodies to tumor-associated and other tissue antigens was described. The method involved: the preparation of solid-phase antigen with cultured (already adhered) or noncultured cells (sedimented by centrifugation) fixed to Micro-Test plates with neutral buffered formaldehyde or absolute methanol; the incubation of the antigen with test or control sera; and the incubation of the antigen with radioiodinated antiglobulin antibody. The nonspecific background of radioactivity was reduced to an acceptable level by the fixed cells being precoated in the wells with 0.5 percent bovine serum albumin in phosphate-buffered saline which was also used for the dilution of sera and labeled antiglobulin antibody. Tumor cells in primary cultures gave a high background, as compared to long-term cultures, which was due to the presence of immunoglobulins (most likely tumor-specific antibody). The specific antibody response to a syngeneic mouse tumor was demonstrated by this technique. (auth)

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage

Science.gov (United States)

Yu, Rui; Lai, Yongquan; Hartwell, Hadley J.; Moeller, Benjamin C.; Doyle-Eisele, Melanie; Kracko, Dean; Bodnar, Wanda M.; Starr, Thomas B.; Swenberg, James A.

2015-01-01

Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N2-hydroxymethyl-dG (N2-HOMe-dG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicity-induced cell proliferation, play important roles in a mutagenic mode of action for cancer. In this study, N2-HOMe-dG was shown to be an excellent biomarker for direct adduction of formaldehyde to DNA and the hydrolysis of DPCs. The use of inhaled [13CD2]-formaldehyde exposures of rats and primates coupled with ultrasensitive nano ultra performance liquid chromatography-tandem mass spectrometry permitted accurate determinations of endogenous and exogenous formaldehyde DNA damage. The results show that inhaled formaldehyde only reached rat and monkey noses, but not tissues distant to the site of initial contact. The amounts of exogenous adducts were remarkably lower than those of endogenous adducts in exposed nasal epithelium. Moreover, exogenous adducts accumulated in rat nasal epithelium over the 28-days exposure to reach steady-state concentrations, followed by elimination with a half-life (t1/2) of 7.1 days. Additionally, we examined artifact formation during DNA preparation to ensure the accuracy of nonlabeled N2-HOMe-dG measurements. These novel findings provide critical new data for understanding major issues identified by the National Research Council Review of the 2010 Environmental Protection Agency’s Draft Integrated Risk Information System Formaldehyde Risk Assessment. They support a data-driven need for reflection on whether risks have been overestimated for inhaled formaldehyde, whereas underappreciating endogenous formaldehyde as the primary source of exposure that results in bone marrow toxicity and leukemia in susceptible humans and rodents deficient in DNA repair. PMID:25904104

Portable formaldehyde monitoring device using porous glass sensor and its applications in indoor air quality studies.

Science.gov (United States)

Maruo, Yasuko Yamada; Nakamura, Jiro

2011-09-30

We have developed a portable device for formaldehyde monitoring with both high sensitivity and high temporal resolution, and carried out indoor air formaldehyde concentration analysis. The absorbance difference of the sensor element was measured in the monitoring device at regular intervals of, for example, one hour or 30 min, and the result was converted into the formaldehyde concentration. This was possible because we found that the lutidine derivative that was formed as a yellow product of the reaction between 1-phenyl-1,3-butandione and formaldehyde was stable in porous glass for at least six months. We estimated the reaction rate and to be 0.049 min(-1) and the reaction occurred quickly enough for us to monitor hourly changes in the formaldehyde concentration. The detection limit was 5 μg m(-3) h. We achieved hourly formaldehyde monitoring using the developed device under several indoor conditions, and estimated the air exchange rate and formaldehyde adsorption rate, which we adopted as a new term in the mass balance equation for formaldehyde, in one office. Copyright © 2011 Elsevier B.V. All rights reserved.

Giant cell tumor of soft tissue: a case report with emphasis on MR imaging

Energy Technology Data Exchange (ETDEWEB)

Lee, Moon Young; Jee, Won-Hee [The Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seocho-gu, Seoul (Korea, Republic of); Jung, Chan Kwon [The Catholic University of Korea, Department of Pathology, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of); Yoo, Ie Ryung [The Catholic University of Korea, Department of Nuclear Medicine, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of); Chung, Yang-Guk [The Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, College of Medicine, Seocho-gu, Seoul (Korea, Republic of)

2015-04-03

Giant cell tumor of soft tissue is a rare neoplasm, histologically resembling giant cell tumor of bone. In this report, we describe a deep and solid giant cell tumor of soft tissue interpreted as a benign soft tissue tumor based on magnetic resonance (MR) findings with hypointense to intermediate signals on T2-weighted images and impeded diffusivity (water movement) on diffusion-weighted imaging (DWI), which could suggest a giant-cell-containing benign soft tissue tumor, despite the malignancy suggested by {sup 18}F-fluorodeoxyglucose positron emission tomography-computed tomography in a 35-year-old male. To our knowledge, this report introduces the first deep, solid giant cell tumor of soft tissue with MR features of a giant-cell-containing benign soft tissue tumor, despite the malignancy-mimicking findings on {sup 18}F-FDG PET-CT. (orig.)

Autocrine Effects of Tumor-Derived Complement

Directory of Open Access Journals (Sweden)

Min Soon Cho

2014-03-01

Full Text Available We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype

Directory of Open Access Journals (Sweden)

Shingo Sato

2016-07-01

Full Text Available The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype.

Treatment of Experimental Brain Tumors with Trombospondin-1 Derived Peptides: an In Vivo Imaging Study

Directory of Open Access Journals (Sweden)

A. Bogdanov, Jr.

1999-11-01

Full Text Available Antiangiogenic and antiproliferative effects of synthetic D-reverse peptides derived from the type 1 repeats of thrombospondin (TSP1 [1,2] were studied in rodent C6 glioma and 9L gliosarcomas. To directly measure tumor size and vascular parameters, we employed in vivo magnetic resonance (MR imaging and corroborated results by traditional morphometric tissue analysis. Rats bearing either C6 or 9L tumors were treated with TSP1-derived peptide (D-reverse amKRFKQDGGWSHWSPWSSac, n=13 or a control peptide (D-reverse am KRAKQAGGASHASPASSac, n=12 at 10 mg/kg, administered either intravenously or through subcutaneous miniosmotic pumps starting 10 days after tumor implantation. Eleven days later, the effect of peptide treatment was evaluated. TSP1 peptide-treated 9L tumors (50.7±44.2 mm3, n=7 and C6 tumors (41.3±34.2 mm3, n=6 were significantly smaller than tumors treated with control peptide (9L: 215.7±67.8 mm3, n=6; C6:184.2±105.2 mm3, n=6. In contrast, the in vivo vascular volume fraction, the mean vascular area (determined by microscopy, and the microvascular density of tumors were not significantly different in any of the experimental groups. In cell culture, TSP1, and the amKRFKQDGGWSHWSPWSSac peptide showed antiproliferative effects against C6 with an IC of 45 nM for TSP1. These results indicate that TSP1derived peptides retard brain tumor growth presumably as a result of slower de novo blood vessel formation and synergistic direct antiproliferative effects on tumor cells. We also show that in vivo MR imaging can be used to assess treatment efficacy of novel antiangiogenic drugs non-invasively, which has obvious implications for clinical trials.

[Fuzzing pattern recognition study on Raman spectrum of tumor peripheral tissue].

Science.gov (United States)

Luo, Lei; Zhao, Yuan-li; Ge, Xiang-hong; Zhang, Xiao-dong; Hao, Zhi-fang; Lü, Jing

2006-06-01

On the basis of some theories about fuzzing pattern recognition, the present article studied the data preprocessing of the Raman spectrum of tumor peripheral tissue, and feature extraction and selection. According to these features the authors improved the leaning towards the bigger membership function of trapezoidal distribution. The authors built the membership function of Raman spectrum of tumor peripheral tissue which belongs to malignant tumor on the basis of 40 specimens, and designed the classifier. The test of other 40 specimens showed that the discrimination of malignant tumor is 82.4%, while that of beginning tumor is 73.9%.

Adsorption of formaldehyde on graphene and graphyne

Science.gov (United States)

Majidi, R.; Karami, A. R.

2014-05-01

The adsorption of formaldehyde on graphene and graphyne was investigated to search high sensitivity sensors for detection of formaldehyde. We have used density functional theory to study the effect of formaldehyde on the electronic properties of graphene and graphyne. It is found that formaldehyde is physisorbed on the graphene and graphyne with small binding energy, large binding distance, and small charge transfer. The calculations also indicate that formaldehyde adsorption modifies the electronic properties of semimetallic graphene, α-graphyne, and β-graphyne and semiconducting γ-graphyne. The graphene and graphyne show semiconducting property in the presence of formaldehyde. The effect of formaldehyde on the electronic properties of graphene and graphyne suggests the potential application of these carbon nanomaterials for formaldehyde detection.

Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

Science.gov (United States)

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

2016-10-01

Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

Formaldehyde Emissions from Urea-Formaldehyde- and no-added-formaldehyde-Bonded particleboard as Influenced by Temperature and Relative Humidity

Science.gov (United States)

Charles R. Frihart; James M. Wescott; Timothy L. Chaffee; Kyle M. Gonner

2012-01-01

It is well documented that temperature and humidity can influence formaldehyde emissions from composite panels that are produced using urea-formaldehyde (UF)–type adhesives. This work investigates the effect of temperature and humidity on newer commercial California Air Resources Board (CARB) phase II–compliant particleboard produced with UF-type adhesives. These...

The expression of Egfl7 in human normal tissues and epithelial tumors.

Science.gov (United States)

Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

2013-04-23

To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

Low-density carbonized resorcinol-formaldehyde foams

International Nuclear Information System (INIS)

Kong, F.M.; Buckley, S.R.; Giles, C.L. Jr.; Haendler, B.L.; Hair, L.M.; Letts, S.A.; Overturf, G.E. III; Price, C.W.; Cook, R.C.

1991-01-01

This report documents research and development on resorcinol- formaldehyde-based foam materials conducted between 1986 and June 1990, when the effort was discontinued. The foams discussed are resorcinol-formaldehyde (RF) foam, carbonized RF (CRF) foam, and two composite foams, a polystyrene/RF (PS/RF) foam and its carbonized derivative (CPR). The RF foams are synthesized by the polycondensation of resorcinol with formaldehyde in a slightly basic solution. Their structure and density depend strongly on the concentration of the sodium carbonate catalyst. The have an interconnected bead structure similar to that of silica aerogels; bead sizes range from 30 to 130 Angstrom, and cell sizes are less than 0.1 μm. We have achieved densities of 16 to 200 mg/cm 3 . The RF foams can be pyrolyzed in an inert atmosphere to form a vitreous carbon foam (CRF), which has a similar microstructure but much higher mechanical strength. The PS/RF foams are obtained by filling the 2- to 3-μm cells of PS foam (a low-density hydrocarbon foam we have developed) with RF. The resultant foams have the outstanding handling and machinability of the PS foam matrix and the small cell size of RF. Pyrolyzing PS/RF foams causes depolymerization and loss of the PS; the resulting CPR foams have a structure similar to the PS foams in which CRF both replicates and fills the PS cells

Detecting somatostatin receptor in breast tumor tissue and its clinical significance

International Nuclear Information System (INIS)

Zhang Yongjian; Yu Xian; Lin Wei; Ding Xuan; Huang Shizhang; Lu Guangming

2002-01-01

The authors observe the difference of somatostatin receptor (SSR) between benign and malignant breast tumor and the relation between SSR and estrogen receptor (ER) or progesterone receptor (PR) in breast tumor tissue, and to predict the clinical value of detecting breast tumor by SSR receptor imaging. These tissues excised from operation in breast tumor were divided into 4 groups: breast malignant tumor group (BMTG) and its control group (C1G), breast benign tumor group (BBTG) and its control group (C2G). SSR was detected by radioligand binding assay (RBA) and ER, PR by LsAB method in these groups. Results is: (1) The SSR express quantity is 108.6 +- 67.3 fmol/mg pr, 37.2 +- 9.6 fmol/mg pr, 43.4 +- 12.6 fmol/mg pr 33.9 +- 10.2 fmol/mg pr respectively in BMTG, C1G, BBTG, C2G. The SSR of BMTG is the most among these groups, the difference is obvious, P 0.05); (2) The correlation coefficient of SSR and ER is 0.859, SSR and PR is 0.750. Most breast tumor tissues express high density SSR, the authors suppose that malignant tumor can been distinguished from benign tumor preliminarily by SSR receptor imaging. There is a good correlation between SSR and ER, PR, detecting SSR may predict the quality of tumor and the prognosis of the patient

Cadmium-109 uptake by tumors derived from Balb C/3T3 cell lines with varying degrees of the transformed phenotype

International Nuclear Information System (INIS)

Morton, K.; Alazraki, N.; Winge, D.; Lynch, R.E.

1986-01-01

To determine if tumors are rich in metallothionein, the authors measured the vivo uptake of subcutaneously-injected carrier-free cadmium-109 in tumors and in normal tissues of Balb/C mice. The tumors were grown in the mice from cultured Balb/3T3 cells transformed by the Moloney murine sarcoma virus. Uptake of cadmium-109 per gram of tissue was greatest for liver, kidney, and spleen. However, tumor uptake of cadmium-109 was markedly greater than that in blood, skeletal muscle, bones, intestine or adipose tissue. B Sephadex G-75 chromatography, the radioactivity in tumor and in liver lysates eluted with cytochrome-C, a molecule similar in molecular weight to metal-lothionein. To determine if metallothionein levels are related to the degree of malignancy of tumors, cadmium-109 uptake in the tumors from the virally-transformed cells was compared to that in tumors from non-transformed Balb/3T3 cells and two derivative chemically transformed cell lines. There was strong correlation between the substrate-independent growth in soft agarose of the four cell lines, the rate of growth of the corresponding tumors, and the amount of cadmium-109 uptake in the tumors. The authors conclude that metallothionein levels may be elevated in tumors as a function of the degree of expression of the transformed phenotype

Formation, Accumulation, and Hydrolysis of Endogenous and Exogenous Formaldehyde-Induced DNA Damage.

Science.gov (United States)

Yu, Rui; Lai, Yongquan; Hartwell, Hadley J; Moeller, Benjamin C; Doyle-Eisele, Melanie; Kracko, Dean; Bodnar, Wanda M; Starr, Thomas B; Swenberg, James A

2015-07-01

Formaldehyde is not only a widely used chemical with well-known carcinogenicity but is also a normal metabolite of living cells. It thus poses unique challenges for understanding risks associated with exposure. N(2-)hydroxymethyl-dG (N(2)-HOMe-dG) is the main formaldehyde-induced DNA mono-adduct, which together with DNA-protein crosslinks (DPCs) and toxicity-induced cell proliferation, play important roles in a mutagenic mode of action for cancer. In this study, N(2)-HOMe-dG was shown to be an excellent biomarker for direct adduction of formaldehyde to DNA and the hydrolysis of DPCs. The use of inhaled [(13)CD2]-formaldehyde exposures of rats and primates coupled with ultrasensitive nano ultra performance liquid chromatography-tandem mass spectrometry permitted accurate determinations of endogenous and exogenous formaldehyde DNA damage. The results show that inhaled formaldehyde only reached rat and monkey noses, but not tissues distant to the site of initial contact. The amounts of exogenous adducts were remarkably lower than those of endogenous adducts in exposed nasal epithelium. Moreover, exogenous adducts accumulated in rat nasal epithelium over the 28-days exposure to reach steady-state concentrations, followed by elimination with a half-life (t1/2) of 7.1 days. Additionally, we examined artifact formation during DNA preparation to ensure the accuracy of nonlabeled N(2)-HOMe-dG measurements. These novel findings provide critical new data for understanding major issues identified by the National Research Council Review of the 2010 Environmental Protection Agency's Draft Integrated Risk Information System Formaldehyde Risk Assessment. They support a data-driven need for reflection on whether risks have been overestimated for inhaled formaldehyde, whereas underappreciating endogenous formaldehyde as the primary source of exposure that results in bone marrow toxicity and leukemia in susceptible humans and rodents deficient in DNA repair. © The Author 2015

Angiofibroma of soft tissue: clinicopathologic study of 2 cases of a recently characterized benign soft tissue tumor.

Science.gov (United States)

Zhao, Ming; Sun, Ke; Li, Changshui; Zheng, Jiangjiang; Yu, Jingjing; Jin, Jie; Xia, Wenping

2013-01-01

Angiofibroma of soft tissue is a very recently characterized, histologically distinctive benign mesenchymal neoplasm of unknown cellular origin composed of 2 principal components, the spindle cell component and very prominent stromal vasculatures. It usually occurs in middle-aged adults, with a female predominance. Herein, we describe the clinical and pathologic details of 2 other examples of this benign tumor. Both patients were middle-aged male and presented with a slow-growing, painless mass located in the deep-seated soft tissue of thigh and left posterior neck region, respectively. Grossly, both tumors were well-demarcated, partial encapsulated of a grayish-white color with firm consistence. Histologically, one case showed morphology otherwise identical to those have been described before, whereas the other case showed in areas being more cellular than most examples of this subtype tumor had, with the lesional cells frequently exhibiting short fascicular, vaguely storiform and occasionally swirling arrangements, which posed a challenging differential diagnosis. Immunostains performed on both tumors did not confirm any specific cell differentiation with lesional cells only reactive for vimentin and focally desmin and negative for all the other markers tested. This report serves to broaden the morphologic spectrum of angiofibroma of soft tumor. Awareness of this tumor is important to prevent misdiagnosis as other more aggressive soft tissue tumor.

Tumors of the connective and supporting tissues

International Nuclear Information System (INIS)

Suit, Herman

1995-01-01

There has been a continuous acceleration of medical/scientific inquiry and of actual improvements in management of patients with neoplasms of the mesenchymal tissues over the last four decades. The number of publications in this field has increased from 1140 in 1970 and then to 1700 in 1990. Important advances discussed over this period include: establishment of sarcoma teams in major oncology centers; staging systems for both soft tissue and osseous sarcomas; demonstration of genetic determinants in the development of, at least, some of the sarcomas; the revolutionary change in quality of diagnostic imaging by the introduction of CT and MRI; use of immunohistochemistry in diagnostic pathology; the drastic gains in survival of patients with osteogenic sarcoma, Ewing's sarcoma and rhabdomyosarcoma due to the efficacy of multi-drug and multi-cycle chemotherapy protocols; major advances in surgical techniques which have made limb salvage practical; cell lines derived from human sarcomas have been shown to have in vitro radiation sensitivity comparable to that of cell lines from epithelial tumors; the combination of conservative surgery and moderate doses of radiation yields local control and survival results equivalent to that of radical surgery with a much improved functional and cosmetic outcome; intra-operative electron beam radiation therapy improves the outcome of patients with retroperitoneal sarcomas when given after grossly complete resection combined with external beam radiation therapy (pre- or post-operatively); radiation is a highly effective alternative to extensive surgery for desmoid tumors; local control of giant cell tumors by modern radiation techniques is ∼ 80% and the incidence of radiation induced tumors at 10 years is ∼ 3%; to decrease the incidence of radiation induced sarcoma, resection has replaced radiation in the management of selected patients with primary Ewing's sarcoma when the response to chemotherapy has been excellent and the

Adipose tissue-derived stem cells in oral mucosa tissue engineering ...

African Journals Online (AJOL)

Jane

2011-10-10

Oct 10, 2011 ... stem cells (ADSCs) may play an important role in this field. In this research ..... Adipose tissue is derived from embryonic mesodermal precursors and .... Clonogenic multipotent stem cells in human adipose tissue differentiate ...

Formaldehyde concentration in diagnostic patch testing

DEFF Research Database (Denmark)

Trattner, A; Johansen, J D; Menné, T

1998-01-01

Exposure to formaldehyde is common from both consumer products and industry. The reliability of the patch test is essential for the diagnosis of formaldehyde allergy as it is difficult to suspect from the patient's history. The recommended formaldehyde patch test concentration has been reduced over...

Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression

Directory of Open Access Journals (Sweden)

Theresa L. Whiteside

2016-10-01

Full Text Available Tumor-derived exosomes (TEX are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions. Although TEX can also stimulate immune activity, in the microenvironments dominated by the tumor, TEX tend to mediate immune suppression thus promoting tumor progression. The TEX content, in part resembling that of the parent cell, may serve as a source of cancer biomarkers. TEX also interfere with immune therapies. A better understanding of TEX and their contribution to cancer progression and cancer patients’ response to immune therapies represents a challenging new field of investigation.

Microfabricated Formaldehyde Gas Sensors

Directory of Open Access Journals (Sweden)

Karen C. Cheung

2009-11-01

Full Text Available Formaldehyde is a volatile organic compound that is widely used in textiles, paper, wood composites, and household materials. Formaldehyde will continuously outgas from manufactured wood products such as furniture, with adverse health effects resulting from prolonged low-level exposure. New, microfabricated sensors for formaldehyde have been developed to meet the need for portable, low-power gas detection. This paper reviews recent work including silicon microhotplates for metal oxide-based detection, enzyme-based electrochemical sensors, and nanowire-based sensors. This paper also investigates the promise of polymer-based sensors for low-temperature, low-power operation.

Phosphorus MRS study in bone and soft-tissue tumors

International Nuclear Information System (INIS)

Du Xiangke; Jiang Baoguo

2000-01-01

Objective: To study the metabolite changes in bone and soft-tissue tumors using phosphorus MRS for better understanding of the phospholipid metabolite and energy metabolite of tumors, which will provide more information for clinical diagnosis and therapy. Methods: Phosphorus MRS and MRI were performed in 14 bone and soft-tissue tumor patients (benign 6, malignant 8) and 19 healthy volunteers at 2.0 T. The areas under the peak of various metabolite in spectra were measured. The ratios of the other metabolite related to β-ATP, ATP, and Pcr were calculated. Intracellular pH was calculated according to the chemical shift change of Pi relative to Pcr. Results: The ratio of PME/β-ATP, PME/ATP, Pcr/PME in both benign and malignant group, intracellular pH in malignant group and LEP/Pcr in benign group were higher than that of the normal group significantly (P < 0.01). the ratios of Pi/Pcr in benign and malignant group, PDE/ATP, PDE/β-ATP, LET/Pcr, Pi/β-ATP in malignant group and LET/β-ATP in benign group were significantly different from that of the normal group (P < 0.05). Between benign and malignant tumors group, the ratios of Pcr/PME and Intracellular pH were different significantly (P < 0.05). Conclusion: The in vivo phosphorus MRS can non-invasively find abnormal phospholipid metabolite, energy metabolite and pH changes in bone and soft tissue tumors

EPIDEMIOLOGY AND SURVIVAL OF PATIENTS WITH MALIGNANT TUMORS OF CONNECTIVE AND SOFT TISSUE

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V. M. Merabishvili

2015-01-01

Full Text Available Introduction. Malignant tumors of connective and soft tissue are met relatively rare, although in general in Russia each year more than 1.500 new cases are registered. On five administrative territories of Russia during a year there are recorded less than 5 new cases of malignant tumors of connective and soft tissue (Yamal-Nenets A.R. – 4; Tuva Republic – 0, Magadan Region – 3; Chukotka A.R. – 0; Jewish A.R. – 4. More seldom data on these patients’ survival are published. Purpose of study. To estimate dynamics of incidence of malignant tumors of connective and soft tissue on the basis of public reporting, to calculate the index accuracy and observed and relative survival rates by histological forms, including sarcomas. Material and methods. To perform a detailed study there were selected, for two periods of observation, respectively 1054 patients (1995–2001 and 919 patients (2002–2008. Estimation of survival was carried out using software, which had been developed together with Ltd. «Novel» (Director – T.L.Tsvetkova, Ph.D.. results of study. The most typical incidence rate for of malignant tumors of connective and soft tissue (S47, 49 that are presented by  cancer registries of different countries is from 1.5 to 2.5 0/   in men and 1.5–2.0 0/   in women. Dynamics  of morbidity of the Russian population, Moscow and St. Petersburg indicates that the level of standardized  incidence rates is in the range of 2.0 0/   in men and within 1.5 0/   in women. The mortality rate in 2013  was respectively for men and women in Russia in total 1.7 0/   and 1.13 0/   , in Moscow – 1.42 0/   and  1.24 0/   , in St. Petersburg – 1.88 0/   and 1.26 0/   . The index accuracy for both sexes in Russia is 0.88,  in Moscow – 1.2; in St. Petersburg – 1.4. This index should be used for the site of these diseases with high fatality. According to official data a one-year lethality of patients with tumors of connective and soft

The potential of tumor-derived exosomes for noninvasive cancer monitoring.

Science.gov (United States)

Whiteside, Theresa L

2015-01-01

Tumor-derived exosomes (TEX) are emerging as a new type of cancer biomarker. TEX are membrane-bound, virus-size vesicles of endocytic origin present in all body fluids of cancer patients. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by tumor cells and cancer cell-specific molecular and genetic contents, TEX are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of tumor cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma of cancer patients responding to therapies appear to correlate with clinical endpoints. However, methods for TEX isolation and separation from the bulk of human plasma-derived exosomes are not yet established and their role as biomarkers remains to be confirmed. Further development and validation of TEX as noninvasive, liquid equivalents of tumor biopsies are necessary to move this effort forward.

Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formmaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages

Science.gov (United States)

ABSTRACT Formaldehyde, a nasal carcinogen, is also an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde rely on internal dose calculations in the upper respiratory tract which ...

SU-D-18A-04: Quantifying the Ability of Tumor Tracking to Spare Normal Tissue

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Burger, A; Buzurovic, I; Hurwitz, M; Williams, C; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical Sc, Boston, MA (United States); Mishra, P [Varian Medical Systems, Palo Alto, CA (United States); Seco, J [Mass General Hospital, Harvard Medical, Boston, MA (United States)

2014-06-01

Purpose: Tumor tracking allows for smaller tissue volumes to be treated, potentially reducing normal tissue damage. However, tumor tracking is a more complex treatment and has little benefit in some scenarios. Here we quantify the benefit of tumor tracking for a range of patients by estimating the dose of radiation to organs at risk and the normal tissue complication probability (NTCP) for both standard and tracking treatment plans. This comparison is performed using both patient 4DCT data and extended Cardiac-Torso (XCAT) digital phantoms. Methods: We use 4DCT data for 10 patients. Additionally, we generate digital phantoms with motion derived from measured patient long tumor trajectories to compare standard and tracking treatment plans. The standard treatment is based on the average intensity projection (AIP) of 4DCT images taken over a breath cycle. The tracking treatment is based on doses calculated on images representing the anatomy at each time point. It is assumed that there are no errors in tracking the target. The NTCP values are calculated based on RTOG guidelines. Results: The mean reduction in the mean dose delivered was 5.5% to the lungs (from 7.3 Gy to 6.9 Gy) and 4.0% to the heart (from 12.5 Gy to 12.0 Gy). The mean reduction in the max dose delivered was 13% to the spinal cord (from 27.6 Gy to 24.0 Gy), 2.5% to the carina (from 31.7 Gy to 30.9 Gy), and 15% to the esophagus (from 69.6 Gy to 58.9 Gy). The mean reduction in the probability of 2nd degree radiation pneumonitis (RP) was 8.7% (3.1% to 2.8%) and the mean reduction in the effective volume was 6.8% (10.8% to 10.2%). Conclusions: Tumor tracking has the potential to reduce irradiation of organs at risk, and consequentially reduce the normal tissue complication probability. The benefits vary based on the clinical scenario. This study is supported by Varian Medical Systems, Inc.

Prevalence of Malignant Soft Tissue Tumors inExtremities: An Epidemiological Study in Syria

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Habib Reshadi

2014-06-01

Full Text Available Background:   Although the majority of soft tissue masses are benign, it is important to consider malignancy in differential diagnoses. Because most soft tissue sarcomas present as a painless mass, clinicians must watch for signs suggestive of malignancy, including large size, rapid growth, and site deep into the deep fascia.The purpose of this study was to determine the relative prevalence according to sex and age, site of tumor, skeletal distribution, and treatment (surgery, chemotherapy and radiotherapy before and after surgery, and ascertain the relative frequency of these tumors in specific anatomic sites and age groups based on pathological studies. Methods: A total of 308 patients, with a musculoskeletal tumor were evaluated retrospectively. All of the patients enrolled into this study were referred to the Beirouni Hospital of Damascus University with a proven diagnosis of alignant soft tissue tumors from the beginning of January 2008 until the end of 2010. The prevalence of the malignant soft tissue tumors in these patients was analyzed. For purposes of analysis, all lesions were placed in 1 of 9 categories: hand and wrist, forearm, humorous (arm, proximal limb girdle (axilla and shoulder, foot and ankle, thigh, hip and buttocks region, trunk, and other lesions. Age and sex also were recorded. Results: Malignant tumors consisted of seven diagnostic categories: malignant fibrous histiocytoma (23%, liposarcoma (22%, rhabdomyosarcoma (9%, leiomyosarcoma (8%, malignant schwannoma (5%, dermatofibrosarcoma protuberans (5%, synovial sarcoma (10%, fibrosarcoma (13%, extraskeletal chondrosarcoma (1%, and extraskeletal Ewing sarcoma (4%. Conclusions: Despite the multitude of pathologic possibilities, most malignant soft-tissue tumors are classified into a small number of diagnoses. These may be further defined when the site of the lesion and the age of the patient are considered. Knowledge of tumor prevalence will assist radiologists in

Prevalence of Malignant Soft Tissue Tumors inExtremities: An Epidemiological Study in Syria

Directory of Open Access Journals (Sweden)

Habib Reshadi

2014-06-01

Full Text Available Background:   Although the majority of soft tissue masses are benign, it is important to consider malignancy in differential diagnoses. Because most soft tissue sarcomas present as a painless mass, clinicians must watch for signs suggestive of malignancy, including large size, rapid growth, and site deep into the deep fascia.The purpose of this study was to determine the relative prevalence according to sex and age, site of tumor, skeletal distribution, and treatment (surgery, chemotherapy and radiotherapy before and after surgery, and ascertain the relative frequency of these tumors in specific anatomic sites and age groups based on pathological studies. Methods: A total of 308 patients, with a musculoskeletal tumor were evaluated retrospectively. All of the patients enrolled into this study were referred to the Beirouni Hospital of Damascus University with a proven diagnosis of alignant soft tissue tumors from the beginning of January 2008 until the end of 2010. The prevalence of the malignant soft tissue tumors in these patients was analyzed. For purposes of analysis, all lesions were placed in 1 of 9 categories: hand and wrist, forearm, humorous (arm, proximal limb girdle (axilla and shoulder, foot and ankle, thigh, hip and buttocks region, trunk, and other lesions. Age and sex also were recorded. Results: Malignant tumors consisted of seven diagnostic categories: malignant fibrous histiocytoma (23%, liposarcoma (22%, rhabdomyosarcoma (9%, leiomyosarcoma (8%, malignant schwannoma (5%, dermatofibrosarcoma protuberans (5%, synovial sarcoma (10%, fibrosarcoma (13%, extraskeletal chondrosarcoma (1%, and extraskeletal Ewing sarcoma (4%. Conclusions: Despite the multitude of pathologic possibilities, most malignant soft-tissue tumors are classified into a small number of diagnoses. These may be further defined when the site of the lesion and the age of the patient are considered. Knowledge of tumor prevalence will assist radiologists in

Scintigraphic evaluation of soft tissue tumors with technetium(V)-99m dimercaptosuccinic acid, a new tumor seeking radiopharmaceutical

International Nuclear Information System (INIS)

Ohta, H.; Yoshizumi, M.; Endo, K.; Torizuka, K.; Yokoyama, A.; Yamamoto, K.

1984-01-01

Recently, a very promising tumor seeking agent, a Tc(V)-99m dimercaptosuccinic acid (Tc(V)-DMS), which was labelled under optimal pH 8 and very low SnCl/sub 2/ concentrations, has been developed. An equilibrium between a stable form and a dissociated form of anion TcO/sub 4//sup 3-/, structural similarity to PO/sub 4//sup 3-/, postulated for tumor uptake. And the authors have previously reported that Tc(V)-DMS scintigram would be useful in the diagnosis of medullary thyroid carcinoma. In an attempt to widen its applicability, the scintigraphic examinations of soft tissue tumors with Tc(V)-DMS and comparative study with Ga-67 citrate were performed in 58 patients. Scintigrams were made 60-120 min after i.v. administration of 10 mCi Tc(V)-DMS using a conventional gamma camera. Tc(V)-DMS was found to have superior sensitivity of 90% for malignant tumors (including aggressive fibromatosis) to that with Ga-67 citrate of 56%, but inferior specificity of 71% to that with Ga-67 citrate of 80%. And the accuracy of the scan in soft tissue tumors with Tc(V)-DMS and Ga-67 citrate was 78% and 71%, respectively. Although the accumulation of Tc(V)-DMS has been detected in some benign soft tissue tumors and the exact mechanism of Tc(V)-DMS accumulation remains to be elucidated, these data indicated that Tc(V)-DMS scintigraphy would be of great use in the detection of extension or location of malignant soft tissue tumors

Dosimetric precision requirements and quantities for characterizing the response of tumors and normal tissues

Energy Technology Data Exchange (ETDEWEB)

Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

1996-08-01

Based on simple radiobiological models the effect of the distribution of absorbed dose in therapy beams on the radiation response of tumor and normal tissue volumes are investigated. Under the assumption that the dose variation in the treated volume is small it is shown that the response of the tissue to radiation is determined mainly by the mean dose to the tumor or normal tissue volume in question. Quantitative expressions are also given for the increased probability of normal tissue complications and the decreased probability of tumor control as a function of increasing dose variations around the mean dose level to these tissues. When the dose variations are large the minimum tumor dose (to cm{sup 3} size volumes) will generally be better related to tumor control and the highest dose to significant portions of normal tissue correlates best to complications. In order not to lose more than one out of 20 curable patients (95% of highest possible treatment outcome) the required accuracy in the dose distribution delivered to the target volume should be 2.5% (1{sigma}) for a mean dose response gradient {gamma} in the range 2 - 3. For more steeply responding tumors and normal tissues even stricter requirements may be desirable. (author). 15 refs, 6 figs.

Regional perfusion and oxygenation of tumors upon methylxanthine derivative administration

International Nuclear Information System (INIS)

Kelleher, Debra K.; Thews, Oliver; Vaupel, Peter

1998-01-01

Purpose: The use of methylxanthine derivatives has been postulated as a means of increasing tumor perfusion and thus ameliorating tumor hypoxia. The aim of this study was to quantify and compare the effects of three methylxanthine derivatives: pentoxifylline (PX), torbafylline (TB), and HWA 138 (HW) on tumor perfusion and oxygenation. Methods and Materials: Anesthetized Sprague Dawley rats with DS-sarcomas implanted subcutaneously onto the hind foot dorsum were used in this study. Mean arterial blood pressure (MABP) was measured throughout experiments. Regional red blood cell (RBC) flux was monitored using a multichannel laser Doppler device and tumor oxygenation on a more global level was assessed polarographically using an O 2 -sensitive catheter electrode. The methylxanthine derivatives were administered as a single dose intraperitoneally (for PX 50 mg/kg; for TB and HW 75 mg/kg). Results: Following drug administration, initial decreases in MABP down to 75% of baseline values were observed for all three substances. PX, HW, and TB caused initial transient reductions in mean RBC flux followed by gradual increases to values of 137 ± 27 %, 139 ± 14 %, and 122 ± 14 % respectively at t = 60 min. Following a small initial decrease upon drug administration, O 2 partial pressure (pO 2 ) rose to 160 ± 31 %, 153 ± 34 %, and 121 ± 11 % for PX, HW, and TB, respectively at t = 60 min. At the end of the observation period (t = 90 min), increases in RBC flux and pO 2 were still evident. When individual tumors were considered, a variety of patterns (including opposing effects) for changes in RBC flux were seen, not necessarily reflected in the mean values. Thus, while the methylxanthine derivatives caused an increased average tumor perfusion, there is evidence suggesting that a redistribution of tumor blood flow occurs which may amplify preexisting heterogeneity. Conclusions: Substantial improvements in tumor oxygenation and perfusion were observed after administration of

On Predicting lung cancer subtypes using ‘omic’ data from tumor and tumor-adjacent histologically-normal tissue

International Nuclear Information System (INIS)

Pineda, Arturo López; Ogoe, Henry Ato; Balasubramanian, Jeya Balaji; Rangel Escareño, Claudia; Visweswaran, Shyam; Herman, James Gordon; Gopalakrishnan, Vanathi

2016-01-01

Adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most prevalent histological types among lung cancers. Distinguishing between these subtypes is critically important because they have different implications for prognosis and treatment. Normally, histopathological analyses are used to distinguish between the two, where the tissue samples are collected based on small endoscopic samples or needle aspirations. However, the lack of cell architecture in these small tissue samples hampers the process of distinguishing between the two subtypes. Molecular profiling can also be used to discriminate between the two lung cancer subtypes, on condition that the biopsy is composed of at least 50 % of tumor cells. However, for some cases, the tissue composition of a biopsy might be a mix of tumor and tumor-adjacent histologically normal tissue (TAHN). When this happens, a new biopsy is required, with associated cost, risks and discomfort to the patient. To avoid this problem, we hypothesize that a computational method can distinguish between lung cancer subtypes given tumor and TAHN tissue. Using publicly available datasets for gene expression and DNA methylation, we applied four classification tasks, depending on the possible combinations of tumor and TAHN tissue. First, we used a feature selector (ReliefF/Limma) to select relevant variables, which were then used to build a simple naïve Bayes classification model. Then, we evaluated the classification performance of our models by measuring the area under the receiver operating characteristic curve (AUC). Finally, we analyzed the relevance of the selected genes using hierarchical clustering and IPA® software for gene functional analysis. All Bayesian models achieved high classification performance (AUC > 0.94), which were confirmed by hierarchical cluster analysis. From the genes selected, 25 (93 %) were found to be related to cancer (19 were associated with ADC or SCC), confirming the biological relevance of our

Radiologic diagnosis of malignant soft-tissue tumors of the extremities

International Nuclear Information System (INIS)

Peters, P.E.; Friedmann, G.

1983-01-01

In malignant soft-tissue tumors of the extremities the radiologist is asked to define size and extent of the lesion and it's relationship to adjacent structures. The assessment of the nature of the lesion is of utmost importance, however, the contribution of the different imaging modalities varies considerably. In a review article the current roles of conventional radiography, xeroradiography, real-time ultrasonography, computed tomography and arteriography in the diagnostic workup of malignant soft-tissue tumors of the extremities are discussed. The statements made are based upon own comparative studies as well as on a review of the literature. In the assessment of the nature of a soft-tissue mass the contribution of all radiologic imaging methods is rather limited, although arteriography may add valuable information if performed complementary to CT. Real-time ultrasonography is well suited to define size, location and extent of peripheral soft-tissue masses. It is therefore recommended as the first imaging method and for follow-up studies. Equivocal findings by real-time sonography and new cases for treatment planning must be confirmed by computed tomography which proved to be the most reliable and the best reproducible imaging method for soft-tissue tumors of the extremities. (orig.)

Tumor imaging and targeting potential of an Hsp70-derived 14-mer peptide.

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Mathias Gehrmann

Full Text Available We have previously used a unique mouse monoclonal antibody cmHsp70.1 to demonstrate the selective presence of a membrane-bound form of Hsp70 (memHsp70 on a variety of leukemia cells and on single cell suspensions derived from solid tumors of different entities, but not on non-transformed cells or cells from corresponding 'healthy' tissue. This antibody can be used to image tumors in vivo and target them for antibody-dependent cellular cytotoxicity. Tumor-specific expression of memHsp70 therefore has the potential to be exploited for theranostic purposes. Given the advantages of peptides as imaging and targeting agents, this study assessed whether a 14-mer tumor penetrating peptide (TPP; TKDNNLLGRFELSG, the sequence of which is derived from the oligomerization domain of Hsp70 which is expressed on the cell surface of tumor cells, can also be used for targeting membrane Hsp70 positive (memHsp70+ tumor cells, in vitro.The specificity of carboxy-fluorescein (CF- labeled TPP (TPP to Hsp70 was proven in an Hsp70 knockout mammary tumor cell system. TPP specifically binds to different memHsp70+ mouse and human tumor cell lines and is rapidly taken up via endosomes. Two to four-fold higher levels of CF-labeled TPP were detected in MCF7 (82% memHsp70+ and MDA-MB-231 (75% memHsp70+ cells compared to T47D cells (29% memHsp70+ that exhibit a lower Hsp70 membrane positivity. After 90 min incubation, TPP co-localized with mitochondrial membranes in memHsp70+ tumors. Although there was no evidence that any given vesicle population was specifically localized, fluorophore-labeled cmHsp70.1 antibody and TPP preferentially accumulated in the proximity of the adherent surface of cultured cells. These findings suggest a potential association between membrane Hsp70 expression and cytoskeletal elements that are involved in adherence, the establishment of intercellular synapses and/or membrane reorganization.This study demonstrates the specific binding and rapid

Exposure of tumor-bearing mice to extremely high-frequency electromagnetic radiation modifies the composition of fatty acids in thymocytes and tumor tissue.

Science.gov (United States)

Gapeyev, Andrew B; Kulagina, Tatiana P; Aripovsky, Alexander V

2013-08-01

To test the participation of fatty acids (FA) in antitumor effects of extremely high-frequency electromagnetic radiation (EHF EMR), the changes in the FA composition in the thymus, liver, blood plasma, muscle tissue, and tumor tissue in mice with Ehrlich solid carcinoma exposed to EHF EMR were studied. Normal and tumor-bearing mice were exposed to EHF EMR with effective parameters (42.2 GHz, 0.1 mW/cm2, 20 min daily during five consecutive days beginning the first day after the inoculation of tumor cells). Fatty acid composition of various organs and tissues of mice were determined using a gas chromatography. It was shown that the exposure of normal mice to EHF EMR or tumor growth significantly increased the content of monounsaturated FA (MUFA) and decreased the content of polyunsaturated FA (PUFA) in all tissues examined. Exposure of tumor-bearing mice to EHF EMR led to the recovery of FA composition in thymocytes to the state that is typical for normal animals. In other tissues of tumor-bearing mice, the exposure to EHF EMR did not induce considerable changes that would be significantly distinguished between disturbances caused by EHF EMR exposure or tumor growth separately. In tumor tissue which is characterized by elevated level of MUFA, the exposure to EHF EMR significantly decreased the summary content of MUFA and increased the summary content of PUFA. The recovery of the FA composition in thymocytes and the modification of the FA composition in the tumor under the influence of EHF EMR on tumor-bearing animals may have crucial importance for elucidating the mechanisms of antitumor effects of the electromagnetic radiation.

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

Science.gov (United States)

Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

2016-05-01

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology.

Science.gov (United States)

Gill, Bartley J; West, Jennifer L

2014-06-27

Cancer progression is mediated by complex epigenetic, protein and structural influences. Critical among them are the biochemical, mechanical and architectural properties of the extracellular matrix (ECM). In recognition of the ECM's important role, cancer biologists have repurposed matrix mimetic culture systems first widely used by tissue engineers as new tools for in vitro study of tumor models. In this review we discuss the pathological changes in tumor ECM, the limitations of 2D culture on both traditional and polyacrylamide hydrogel surfaces in modeling these characteristics and advances in both naturally derived and synthetic scaffolds to facilitate more complex and controllable 3D cancer cell culture. Studies using naturally derived matrix materials like Matrigel and collagen have produced significant findings related to tumor morphogenesis and matrix invasion in a 3D environment and the mechanotransductive signaling that mediates key tumor-matrix interaction. However, lack of precise experimental control over important matrix factors in these matrices have increasingly led investigators to synthetic and semi-synthetic scaffolds that offer the engineering of specific ECM cues and the potential for more advanced experimental manipulations. Synthetic scaffolds composed of poly(ethylene glycol) (PEG), for example, facilitate highly biocompatible 3D culture, modular bioactive features like cell-mediated matrix degradation and complete independent control over matrix bioactivity and mechanics. Future work in PEG or similar reductionist synthetic matrix systems should enable the study of increasingly complex and dynamic tumor-ECM relationships in the hopes that accurate modeling of these relationships may reveal new cancer therapeutics targeting tumor progression and metastasis. © 2013 Published by Elsevier Ltd.

MR imaging of uncommon soft tissue tumors in the foot: a pictorial essay

Energy Technology Data Exchange (ETDEWEB)

Lee, Youn Joo; Chun, Kyung Ah; Kim, Jee Young; Sung, Mi Sook; Kim, Ki Tae [The Catholic University of Korea, Uijeongbu (Korea, Republic of)

2007-06-15

The large variety of masses occur in the foot. The foot is a comparatively rare site of soft tissue neoplasms. MRI has greatly improved the ability to detect and delineate soft tissue lesions and is now considered the gold-standard imaging technique in their investigation. Recently, we have encountered rare soft tissue tumors of the foot. The presented cases include benign masses such as granuloma annulare, angiomyoma, neural fibrolipoma, and giant cell tumor of tendon sheath, as well as malignant tumors such as melanoma, synovial sarcoma, rhabdomyosarcoma and extraskeletal myxoid chondrosarcoma. We wish to illustrate the MR findings of these uncommon soft tissue mors to aid in their diagnosis.

Spectral staining of tumor tissue by fiber optic FTIR spectroscopy

Science.gov (United States)

Salzer, Reiner; Steiner, Gerald; Kano, Angelique; Richter, Tom; Bergmann, Ralf; Rodig, Heike; Johannsen, Bernd; Kobelke, Jens

2003-07-01

Infrared (IR) optical fiber have aroused great interest in recent years because of their potential in in-vivo spectroscopy. This potential includes the ability to be flexible, small and to guide IR light in a very large range of wavelengths. Two types - silver halide and chalcogenide - infrared transmitting fibers are investigated in the detection of a malignant tumor. As a test sample for all types of fibers we used a thin section of an entire rat brain with glioblastoma. The fibers were connected with a common infrared microscope. Maps across the whole tissue section with more than 200 spectra were recorded by moving the sample with an XY stage. Data evaluation was performed using fuzzy c-means cluster analysis (FCM). The silver halide fibers provided excellent results. The tumor was clearly discernible from healthy tissue. Chalcogenide fibers are not suitable to distinguish tumor from normal tissue because the fiber has a very low transmittance in the important fingerprint region.

Formaldehyde-related clinical symptoms reported by medical students during gross anatomy cadaver dissection

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Łukasz Pietrzyk

2016-09-01

Full Text Available Introduction . Formaldehyde is a noxious gas used as a tissue preservative of cadavers in autopsy rooms. Therefore, exposure to higher concentrations applies particularly to laboratory staff, anatomists and medical students. Prolonged exposure to formaldehyde is associated with clinical complications. Objective. To assess whether exposure to repeated inhalation of low concentrations of formaldehyde (FA experienced during a gross anatomy course triggers subjective clinical symptoms in medical students. Material and methods . All 198 first-year medical students of the Medical University of Lublin, Poland (28% with allergy history and 72% without allergy history; 69% male and 31% female responded to a questionnaire concerning their subjective FA-related clinical symptoms. Differences in proportions of experienced symptoms between allergic vs. nonallergic, and female vs. males were compared by the Mann-Whitney U test. Results . Even though formaldehyde concentrations in the gross anatomy laboratory were relatively low (0.47–0.57 mg/m3, medical students experienced various reactions (lacrimation in 85.9%, red eyes, dry and itchy eyes, runny nose, sneezing, and headache in > 50% of students, cough in 44%, and dry throat or throat irritation in 42% of students. Among students with a history of allergy, eye, nose, skin and respiratory system symptoms occurred more frequently in comparison to nonallergic students. Female individuals demonstrated higher sensitivity to FA exposure. Conclusions . Exposure to formaldehyde may result in development of clinical symptoms in medical students. Particularly unpleasant symptoms may be experienced by individuals with allergy history. It is necessary to decrease formaldehyde concentrations in the anatomy dissection laboratory.

Wilms tumor arising in extracoelomic paravertebral soft tissues.

LENUS (Irish Health Repository)

Mulligan, Linda

2012-02-01

Extrarenal Wilms tumor (ERWT) is a well-established entity which most commonly arises within the genitourinary tract, including intracoelomic paranephric soft tissue. Rarely, ERWT arises within teratoma, and it tends to occur predominantly in distinct settings, such as females with spinal defects and males with testicular teratomas. We report a unique ERWT arising within an extracoelomic teratoma of the paraspinal musculature, thereby expanding the range of reported locations for this unusual tumor.

Field Derived Emission Factors For Formaldehyde and other Volatile Organic Compounds in FEMA Temporary Housing Units

Energy Technology Data Exchange (ETDEWEB)

Parthasarathy, Srinandini; Maddalena, Randy L.; Russell, Marion L.; Apte, Michael G.

2010-10-01

Sixteen previously occupied temporary housing units (THUs) were studied to assess emissions of volatile organic compounds. The whole trailer emission factors wereevaluated for 36 VOCs including formaldehyde. Indoor sampling was carried out in the THUs located in Purvis staging yard in Mississippi, USA. Indoor temperature andrelative humidity (RH) were also measured in all the trailers during sampling. Indoor temperatures were varied (increased or decreased) in a selection of THUs using theheating, ventilation and air conditioning (HVAC) systems. Indoor temperatures during sampling ranged from 14o C to 33o C, and relative humidity (RH) varied between 35percentand 74percent. Ventilation rates were increased in some trailers using bathroom fans and vents during some of the sampling events. Ventilation rates measured during some aselection of sampling events varied from 0.14 to 4.3 h-1. Steady state indoor formaldehyde concentrations ranged from 10 mu g-m-3 to 1000 mu g-m-3. The formaldehyde concentrations in the trailers were of toxicological significance. The effects of temperature, humidity and ventilation rates were also studied. A linearregression model was built using log of percentage relative humidity, inverse of temperature (in K-1), and inverse log ACH as continuous independent variables, trailermanufacturer as a categorical independent variable, and log of the chemical emission factors as the dependent variable. The coefficients of inverse temperature, log relativehumidity, log inverse ACH with log emission factor were found to be statistically significant for all the samples at the 95percent confidence level. The regression model wasfound to explain about 84percent of the variation in the dependent variable. Most VOC concentrations measured indoors in the Purvis THUs were mostly found to be belowvalues reported in earlier studies by Maddalena et al.,1,2 Hodgson et al.,3 and Hippelein4. Emissions of TMPB-DIB (a plasticizer found in vinyl products) were found

The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas

International Nuclear Information System (INIS)

Nordsmark, Marianne; Hoeyer, Morten; Keller, Johnny; Nielsen, Ole Steen; Jensen, Oluf Myhre; Overgaard, Jens

1996-01-01

Purpose: In malignant tumors the oxygenation status and tumor cell proliferation are known to influence local tumor control after radiotherapy. However, the relationship between oxygenation status and tumor cell kinetics in human tumors has not yet been described. Newly developed clinically applicable techniques such as oxygen electrode measurements and assessment of tumor cell proliferation rates have been suggested as promising predictive assays. The purpose of the present study was to characterize tumor oxygenation status in soft tissue sarcomas and to compare this with tumor cell kinetics and clinical parameters. Methods and Materials: Pretreatment tumor oxygenation status was measured by polarographic oxygen needle electrodes and evaluated as the median pO 2 and the percentage of pO 2 values ≤ 5 mmHg and ≤ 2.5 mmHg in 22 patients with primary soft tissue sarcomas. All tumors were characterized by histology, grade of malignancy, the level of microscopic necrosis, the level of effective hemoglobin, and magnetic resonance imaging estimation of tumor volume. The tumor cell potential doubling time and labeling index were measured by flow cytometric and immunohistochemical analysis of tumor biopsy specimens after in vivo incorporation of iododeoxyuridine. Results: There was a significant correlation between the median pO 2 and the tumor cell potential doubling time (p = 0.041), whereas no correlation was found between the level of hypoxia expressed by the percentage of pO 2 values ≤ 2.5 and ≤ 5 mmHg, respectively, and tumor cell potential doubling time. Furthermore, no correlation was found between either of the three tumor oxygenation parameters and labeling index. The material represented large intertumor heterogeneity in oxygenation status, cell kinetics, and tumor volume, and no correlation was found between oxygenation status and either volume, histopathology, grade of malignancy, or effective hemoglobin. Conclusion: This report is the first to suggest

Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression

Directory of Open Access Journals (Sweden)

Rute M.M. Ferreira

2017-10-01

Full Text Available The cell of origin of pancreatic ductal adenocarcinoma (PDAC has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs, duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development.

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue

International Nuclear Information System (INIS)

Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

1983-01-01

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy

Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization.

Science.gov (United States)

Wang, Sheng; Huang, Peng; Chen, Xiaoyuan

2016-09-01

Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modern concepts for basic radiobiological factors characterizing tumor tissue radiosensitivity

International Nuclear Information System (INIS)

Gocheva, L.; Sergieva, K.

2002-01-01

Traditionally radiotherapy is prescribed at doses consistent with the expected therapeutic response and tolerance of tumor and normal tissues without consideration to individual differences in radiosensitivity. However, the basic radiobiological knowledge and clinical experience along this line point to significant variations in the observed therapeutic results. It has been established that cells and tissues under experimental and clinical conditions manifest a wide spectrum of individual radiosensitivity. The aim of this survey is to outline the current concepts for the basic radiobiological factors influencing tumor radiosensitivity. A thorough discussion is done of the essence, mechanisms of action, methods of determination and measurement, and effect on the prognosis in patients with malignant diseases of a number of radiobiological factors, such as: tumor-cell proliferation, apoptosis, tumor hypoxia and neovascularization. Although the knowledge of the mechanisms of radiosensitivity is constantly expanding, its clinical implementation is still rather limited. The true role of radiosensitivity in predicting the therapeutic response should be more accurately defined. (authors)

NUTM1 Gene Fusions Characterize a Subset of Undifferentiated Soft Tissue and Visceral Tumors.

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Dickson, Brendan C; Sung, Yun-Shao; Rosenblum, Marc K; Reuter, Victor E; Harb, Mohammed; Wunder, Jay S; Swanson, David; Antonescu, Cristina R

2018-05-01

NUT midline carcinoma is an aggressive tumor that occurs mainly in the head and neck and, less frequently, the mediastinum and lung. Following identification of an index case of a NUTM1 fusion positive undifferentiated soft tissue tumor, we interrogated additional cases of primary undifferentiated soft tissue and visceral tumors for NUTM1 abnormalities. Targeted next-generation sequencing was performed on RNA extracted from formalin-fixed paraffin-embedded tissue, and results validated by fluorescence in situ hybridization using custom bacterial artificial chromosome probes. Six patients were identified: mean age of 42 years (range, 3 to 71 y); equal sex distribution; and, tumors involved the extremity soft tissues (N=2), kidney (N=2), stomach, and brain. On systemic work-up at presentation all patients lacked a distant primary tumor. Morphologically, the tumors were heterogenous, with undifferentiated round-epithelioid-rhabdoid cells arranged in solid sheets, nests, and cords. Mitotic activity was generally brisk. Four cases expressed pancytokeratin, but in only 2 cases was this diffuse. Next-generation sequencing demonstrated the following fusions: BRD4-NUTM1 (3 cases), BRD3-NUTM1, MXD1-NUTM1, and BCORL1-NUTM1. Independent testing by fluorescence in situ hybridization confirmed the presence of NUTM1 and partner gene rearrangement. This study establishes that NUT-associated tumors transgress the midline and account for a subset of primitive neoplasms occurring in soft tissue and viscera. Tumors harboring NUTM1 gene fusions are presumably underrecognized, and the extent to which they account for undifferentiated mesenchymal, neuroendocrine, and/or epithelial neoplasms is unclear. Moreover, the relationship, if any, between NUT-associated tumors in soft tissue and/or viscera, and conventional NUT carcinoma, remains to be elucidated.

Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.

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Kami, Kenjiro; Fujimori, Tamaki; Sato, Hajime; Sato, Mutsuko; Yamamoto, Hiroyuki; Ohashi, Yoshiaki; Sugiyama, Naoyuki; Ishihama, Yasushi; Onozuka, Hiroko; Ochiai, Atsushi; Esumi, Hiroyasu; Soga, Tomoyoshi; Tomita, Masaru

2013-04-01

Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified. Metabolomic profiles of lung and prostate tissues comprised 114 and 86 metabolites, respectively, and the profiles not only well distinguished tumor from normal tissues, but also squamous cell carcinoma from the other tumor types in lung cancer and poorly differentiated tumors from moderately differentiated tumors in prostate cancer. Concentrations of most amino acids, especially branched-chain amino acids, were significantly higher in tumor tissues, independent of organ type, but of essential amino acids were particularly higher in poorly differentiated than moderately differentiated prostate cancers. Organ-dependent differences were prominent at the levels of glycolytic and tricarboxylic acid cycle intermediates and associated energy status. Significantly high lactate concentrations and elevated activating phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based metabolomics combined with phosphorylated enzyme analysis for understanding tissue-specific tumor microenvironments, which may lead to the development of more effective and specific anticancer therapeutics.

Three-Dimensional Patient-Derived In Vitro Sarcoma Models: Promising Tools for Improving Clinical Tumor Management

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Manuela Gaebler

2017-09-01

Full Text Available Over the past decade, the development of new targeted therapeutics directed against specific molecular pathways involved in tumor cell proliferation and survival has allowed an essential improvement in carcinoma treatment. Unfortunately, the scenario is different for sarcomas, a group of malignant neoplasms originating from mesenchymal cells, for which the main therapeutic approach still consists in the combination of surgery, chemotherapy, and radiation therapy. The lack of innovative approaches in sarcoma treatment stems from the high degree of heterogeneity of this tumor type, with more that 70 different histopathological subtypes, and the limited knowledge of the molecular drivers of tumor development and progression. Currently, molecular therapies are available mainly for the treatment of gastrointestinal stromal tumor, a soft-tissue malignancy characterized by an activating mutation of the tyrosine kinase KIT. Since the first application of this approach, a strong effort has been made to understand sarcoma molecular alterations that can be potential targets for therapy. The low incidence combined with the high level of histopathological heterogeneity makes the development of clinical trials for sarcomas very challenging. For this reason, preclinical studies are needed to better understand tumor biology with the aim to develop new targeted therapeutics. Currently, these studies are mainly based on in vitro testing, since cell lines, and in particular patient-derived models, represent a reliable and easy to handle tool for investigation. In the present review, we summarize the most important models currently available in the field, focusing in particular on the three-dimensional spheroid/organoid model. This innovative approach for studying tumor biology better represents tissue architecture and cell–cell as well as cell–microenvironment crosstalk, which are fundamental steps for tumor cell proliferation and survival.

Oxygen diffusion and oxygen effect in tumor tissue

International Nuclear Information System (INIS)

Eissa, H.M.; Hehn, G.

1979-06-01

The diffusion of oxygen in tumor cords of bronchus carcinoma of the lung have been studied with refined computer methods for solving the diffusion equation in axis symmetric tumor structures. In this tumor configuration we may find three different regions consisting of euoxic cells, hypoxic tumor cells and necrotic parts. In the case of oxygen supply from a capillary inside a cylinder of tumor tissue with radius 200 μm or in a tumor cord of radius 300 μm with oxygen supply by capillaries outside, we get a relation of well oxygenated cells to hypoxic cells approximately as 1:8 or as 1:1.1 respectively. Of course most of the tumor cords observed in histological slices have smaller diameters, so that an average of approximately 20% hypoxic cells can be assumed. Based on the work of Ardenne, the diffusion of oxygen and glucose in a tumor of type DS-carcinosarcom has been investigated in both intact tumor and tumor treated with ionizing radiation. We can show that a strong reoxygenation effect takes place in that the well supplied regions may increase in some tumor configurations up to a factor of four by volume. The biological consequences of the oxygen pressure determined in tumor cells are discussed in detail. The investigation of oxygen diffusion in the intercapillary tumor region should give a quantitative physical basis for considering the oxygen effect with the aim to explain the advantages of neutron therapy against conventional radiotherapy. (orig./MG) [de

Emission of formaldehyde from furniture

DEFF Research Database (Denmark)

Andersen, Helle Vibeke; Klinke, Helene B.; Funch, Lis Winther

The emission of formaldehyde from 20 pieces of furniture, representing a variety of types, was measured in climate chambers. Most tests show low emissions but certain scenarios of furnishing, including furniture with large surface areas in relation to room volume can emit formaldehyde resulting...

Subungual Hypervascular Soft Tissue Chondroma Mimicking a Glomus Tumor: A Case Report

International Nuclear Information System (INIS)

Park, Jong Chun; Lee, Young Hwan; Jung, Kyung Jae

2009-01-01

Soft tissue chondroma, or extraskeletal chondroma, is a relatively rare, benign cartilaginous tumor that occurs most frequently in the hands and feet - a subungual location is quite rare. The authors describe a subungual soft tissue chondroma in a 25-year-old man that was visualized as a hypervascular mass on color Doppler ultrasonography and initially misdiagnosed as a glomus tumor

Subungual Hypervascular Soft Tissue Chondroma Mimicking a Glomus Tumor: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Park, Jong Chun; Lee, Young Hwan; Jung, Kyung Jae [Catholic University of Daegu, School of Medicine, Daegu (Korea, Republic of)

2009-09-15

Soft tissue chondroma, or extraskeletal chondroma, is a relatively rare, benign cartilaginous tumor that occurs most frequently in the hands and feet - a subungual location is quite rare. The authors describe a subungual soft tissue chondroma in a 25-year-old man that was visualized as a hypervascular mass on color Doppler ultrasonography and initially misdiagnosed as a glomus tumor

Epo receptors are not detectable in primary human tumor tissue samples.

Directory of Open Access Journals (Sweden)

Steve Elliott

Full Text Available Erythropoietin (Epo is a cytokine that binds and activates an Epo receptor (EpoR expressed on the surface of erythroid progenitor cells to promote erythropoiesis. While early studies suggested EpoR transcripts were expressed exclusively in the erythroid compartment, low-level EpoR transcripts were detected in nonhematopoietic tissues and tumor cell lines using sensitive RT-PCR methods. However due to the widespread use of nonspecific anti-EpoR antibodies there are conflicting data on EpoR protein expression. In tumor cell lines and normal human tissues examined with a specific and sensitive monoclonal antibody to human EpoR (A82, little/no EpoR protein was detected and it was not functional. In contrast, EpoR protein was reportedly detectable in a breast tumor cell line (MCF-7 and breast cancer tissues with an anti-EpoR polyclonal antibody (M-20, and functional responses to rHuEpo were reported with MCF-7 cells. In another study, a functional response was reported with the lung tumor cell line (NCI-H838 at physiological levels of rHuEpo. However, the specificity of M-20 is in question and the absence of appropriate negative controls raise questions about possible false-positive effects. Here we show that with A82, no EpoR protein was detectable in normal human and matching cancer tissues from breast, lung, colon, ovary and skin with little/no EpoR in MCF-7 and most other breast and lung tumor cell lines. We show further that M-20 provides false positive staining with tissues and it binds to a non-EpoR protein that migrates at the same size as EpoR with MCF-7 lysates. EpoR protein was detectable with NCI-H838 cells, but no rHuEpo-induced phosphorylation of AKT, STAT3, pS6RP or STAT5 was observed suggesting the EpoR was not functional. Taken together these results raise questions about the hypothesis that most tumors express high levels of functional EpoR protein.

Increased PADI4 expression in blood and tissues of patients with malignant tumors

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Zhao Yan

2009-01-01

Full Text Available Abstract Background Peptidylarginine deiminase type 4 (PAD4/PADI4 post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Methods Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673 as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT were investigated in the blood of patients with various tumors by ELISA (n = 1121. Results Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with

Increased PADI4 expression in blood and tissues of patients with malignant tumors

International Nuclear Information System (INIS)

Chang, Xiaotian; Han, Jinxiang; Pang, Li; Zhao, Yan; Yang, Yi; Shen, Zhonglin

2009-01-01

Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121). Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors compared to those in patients

The Diagnostic and Prognostic Value of Hematological and Chemical Abnormalities in Soft Tissue Sarcoma: A Comparative Study in Patients with Benign and Malignant Soft Tissue Tumors.

Science.gov (United States)

Ariizumi, Takashi; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Hatano, Hiroshi; Morita, Tetsuro; Endo, Naoto

2018-01-01

The value of routine blood tests in malignant soft tissue tumors remains uncertain. To determine if these tests can be used for screening, the routine pretreatment blood test findings were retrospectively investigated in 359 patients with benign and malignant soft tissue tumors. Additionally, the prognostic potential of pretreatment blood abnormalities was evaluated in patients with soft tissue sarcomas. We compared clinical factors and blood tests findings between patients with benign and malignant soft tissue tumors using univariate and multivariate analysis. Subsequently, patients with malignant tumors were divided into two groups based on blood test reference values, and the prognostic significance of each parameter was evaluated. In the univariate analysis, age, tumor size, and tumor depth were significant clinical diagnostic factors. Significant increases in the granulocyte count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and γ-glutamyl transpeptidase (γ-GTP) levels were found in patients with malignant soft tissue tumors. Multiple logistic regression showed that tumor size and ESR were independent factors that predicted malignant soft tissue tumors. The Kaplan-Meier survival analysis revealed that granulocyte counts, γ-GTP levels, and CRP levels correlated significantly with overall survival. Thus, pretreatment routine blood tests are useful diagnostic and prognostic markers for diagnosing soft tissue sarcoma. © 2018 by the Association of Clinical Scientists, Inc.

[Comparison of paired box genes 8 and 2 expression in epithelium tissues and the related tumors].

Science.gov (United States)

Song, Y; Huang, X; Shen, G H; Liu, X Y; Zhang, X

2017-06-23

Objective: To explore the expressional differences between paired box genes 2(Pax2) and 8 (Pax8) protein in different kinds of epitheliums and tumors, and to investigate the clinicopathologic significance. Methods: Expression levels of Pax2 and Pax8 protein were detected in 75 cases of different human epithelium tissues and 255 cases of different tumors on tissue microarray by immunohistochemistry. Results: Pax2 and Pax8 selectively expressed in different tissues. The positive rates of Pax8 protein expressed in the normal epithelium of the thyroid, urinary system and female reproductive system were 100% (2/2), 60.0% (3/5) and 76.9% (10/13), respectively. The positive rates of Pax2 expressed in the epithelium tissues of urinary system and the female reproductive system were 40.0% (2/5) and 38.5% (5/13) respectively. However, the expression of Pax2 protein was not detected in the normal thyroid epithelium. The positive rate of Pax8 protein expressing in the epithelium of reproductive system was significantly higher than that of Pax2 protein ( P <0.05). The tumors derived from different tissues also expressed different levels of protein Pax2 and Pax8. The positive rates of Pax8 in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were 65.2% (15/23), 66.7% (10/15) and 80.0% (4/5), respectively. The positive rates of Pax2 in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were 34.8% (8/23), 13.3% (2/15) and 20.0% (1/5), respectively. The positive rates of Pax8 protein expressed in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were significantly higher than those of Pax2 protein ( P <0.05). The positive rates of Pax8 in ovarian serous carcinoma, endometrial carcinoma and clear cell carcinoma were 92.9% (26/28), 81.8% (9/11) and 82.4% (14/17), respectively. The positive rates of Pax2 in ovarian serous carcinoma, endometrial carcinoma and clear cell carcinoma were 28.6% (8/28), 9.1% (1/11) and 17.6% (3

Application of infrared spectroscopy for diagnosis of kidney tumor tissue

OpenAIRE

Bandzevičiūtė, Rimantė

2016-01-01

Application of Infrared Spectroscopy for Diagnosis of Kidney Tumor Tissue It is possible to apply the technique of an attenuated total reflection of infrared radiation (ATR IR) for the characterisation of the removed tissues during the surgery. Application of this method for interstitium of the removed tissue does not require any specific sample preparation. For this reason ATR IR technique applied for the interstitium allows to get information about tissues immediately after surgical operati...

NMR studies of proton exchange kinetics in aqueous formaldehyde solutions.

Science.gov (United States)

Rivlin, Michal; Eliav, Uzi; Navon, Gil

2014-05-01

Aqueous solutions of formaldehyde, formalin, are commonly used for tissue fixation and preservation. Treatment with formalin is known to shorten the tissue transverse relaxation time T2. Part of this shortening is due to the effect of formalin on the water T2. In the present work we show that the shortening of water T2 is a result of proton exchange between water and the major constituent of aqueous solutions of formaldehyde, methylene glycol. We report the observation of the signal of the hydroxyl protons of methylene glycol at 2ppm to high frequency of the water signal that can be seen at low temperatures and at pH range of 6.0±1.5 and, at conditions where it cannot be observed by the single pulse experiment, it can be detected indirectly through the water signal by the chemical exchange saturation transfer (CEST) experiment. The above finding made it possible to obtain the exchange rate between the hydroxyl protons of the methylene glycol and water in aqueous formaldehyde solutions, either using the dispersion of the spin-lattice relaxation rate in the rotating frame (1/T1ρ) or, at the slow exchange regime, from the line width hydroxyl protons of methylene glycol. The exchange rate was ∼10(4)s(-1) at pH 7.4 and 37°C, the activation energy, 50.2kJ/mol and its pH dependence at 1.1°C was fitted to: k (s(-1))=520+6.5×10(7)[H(+)]+3.0×10(9)[OH(-)]. Copyright © 2014. Published by Elsevier Inc.

Gene Expression Analysis of Immunostained Endothelial Cells Isolated from Formaldehyde-fixated Paraffin Embedded Tumors Using Laser Capture Microdissection – a Technical Report

Science.gov (United States)

Kaneko, Tomoatsu; Okiji, Takashi; Kaneko, Reika; Suda, Hideaki; Nör, Jacques E.

2009-01-01

Laser capture microdissection (LCM) allows microscopic procurement of specific cell types from tissue sections that can then be used for gene expression analysis. In conventional LCM, frozen tissues stained with hematoxylin are normally used to the molecular analysis. Recent studies suggested that it is possible to carry out gene expression analysis of formaldehyde-fixated paraffin embedded (FFPE) tissues that were stained with hematoxylin. However, it is still unclear if quantitative gene expression analyses can be performed from LCM cells from FFPE tissues that were subjected to immunostaining to enhance identification of target cells. In this proof-of-principle study, we analyzed by RT-PCR and real time PCR the expression of genes in factor VIII immunostained human endothelial cells that were dissected from FFPE tissues by LCM. We observed that immunostaining should be performed at 4°C to preserve the mRNA from the cells. The expression of Bcl-2 in the endothelial cells was evaluated by RT-PCR and by real time PCR. GAPDH and 18S were used as house keeping genes for RT-PCR and real time PCR, respectively. This report unveils a method for quantitative gene expression analysis in cells that were identified by immunostaining and retrieved by LCM from FFPE tissues. This method is ideally suited for the analysis of relatively rare cell types within a tissue, and should improve on our ability to perform differential diagnosis of pathologies as compared to conventional LCM. PMID:19425073

A nonphosphaturic mesenchymal tumor mixed connective tissue variant of the sacrum.

Science.gov (United States)

Mavrogenis, Andreas F; Sakellariou, Vasileios I; Soultanis, Konstantinos; Mahera, Helen; Korres, Demetrios S; Papagelopoulos, Panayiotis J

2010-11-02

Tumor-induced or oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by overproduction of fibroblast growth factor-23 as a phosphaturic agent and renal phosphate wasting. A range of predominantly mesenchymal neoplasms have been associated with tumor-induced osteomalacia and classified as phosphaturic mesenchymal tumor mixed connective tissues. However, phosphaturic mesenchymal tumor mixed connective tissues could be nonphosphaturic in the first stage of the disease, either because the tumors are resected early in the clinical course or because the patient's osteomalacia was attributed to another cause. This article presents a case of a 42-year-old woman with a 2-year history of low back and right leg pain. Laboratory examinations including serum and urine calcium and phosphorous were within normal values. Imaging of the lumbar spine and pelvis showed an osteolytic lesion occupying the right sacral wing. Histology was unclear. Reverse-transcription polymerase chain reaction analysis for fibroblast growth factor-23 was positive and confirmed the diagnosis of phosphaturic mesenchymal tumor mixed connective tissues. Preoperative selective arterial embolization and complete intralesional excision, bone grafting, and instrumented fusion from L4 to L5 to the iliac wings bilaterally was performed. Postoperative recovery was uneventful. Neurological deficits were not observed. A lumbopelvic corset was applied for 3 months. At 12 months, the patient was asymptomatic. Serum and urine values of calcium and phosphorous were normal throughout the follow-up evaluation. Copyright 2010, SLACK Incorporated.

Hypoxic Response of Tumor Tissues in a Microfluidic Environment

Science.gov (United States)

Morshed, Adnan; Dutta, Prashanta

2017-11-01

Inside a tumor tissue, cells growing further away from the blood vessel often suffer from low oxygen levels known as hypoxia. Cancer cells have shown prolonged survival in hostile hypoxic conditions by sharply changing the cellular metabolism. In this work, different stages of growth of the tumor tissue and the oxygen transport across the tissue are investigated. The tissue was modeled as a contiguous block of cells inside a microfluidic environment with nutrient transport through advection and diffusion. While oxygen uptake inside the tissue is through diffusion, ascorbate transport from the extracellular medium is addressed by a concentration dependent uptake model. By varying the experimentally observed oxygen consumption rate, different types of cancer cells and their normoxic and hypoxic stages were studied. Even when the oxygen supply in the channel is maintained at normoxic levels, our results show the onset of hypoxia within minutes inside the cellblock. Interestingly, modeled cell blocks with and without a structured basal layer showed less than 5% variation in hypoxic response in chronic hypoxia. Results also indicate that the balance of cell survival and growth are affected by the flow rate of nutrients and the oxygen consumption rate. This work was supported in part by the National Science Foundation under Grant No. DMS 1317671.

Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

Science.gov (United States)

Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

2013-07-01

Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

Radiation thermal transformations of formaldehyde in alcohols

International Nuclear Information System (INIS)

Vetrov, V.S.; Korolev, V.M.; Koroleva, G.N.; Likholap, V.F.; Khomich, F.G.

1978-01-01

The effect of acid and reactor gamma radiation on the interaction of formaldehyde and methanol has been studied. The radiation-thermal investigations were carried out in the range of temperatures from 150 to 230 deg C. A dose rate of n,γ-radiation amounted to 2.4x10 17 eV (gxs). From the data obtained it is concluded that the 0.01-0.1 M formic acid addition and irradiation of the methanol-formaldehyde mixture result in a substantial increase in formaldehyde consumption, the acid addition increasing the rate of formaldehyde consumption in about two times; the n,γ-radiation effect is much powerful. The rate of methylal formation increases in the presence of acid and at the temperature rise; its maximum is formed in the range of 180-190 deg C. The methyl formiate formation increases with the acid addition and temperature rise. It is concluded that radiolytic protons can accelerate methylal formation from methanol-formaldehyde solutions. The temperature rise results in the concentration increase in a free form of formaldehyde and the formation of methylal and methyl formiate

Acellular organ scaffolds for tumor tissue engineering

Science.gov (United States)

Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

2015-12-01

Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

Connective tissue of cervical carcinoma xenografts: associations with tumor hypoxia and interstitial fluid pressure and its assessment by DCE-MRI and DW-MRI.

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Hompland, Tord; Ellingsen, Christine; Galappathi, Kanthi; Rofstad, Einar K

2014-01-01

Abstract Background. A high fraction of stroma in malignant tissues is associated with tumor progression, metastasis, and poor prognosis. Possible correlations between the stromal and physiologic microenvironments of tumors and the potential of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in quantification of the stromal microenvironment were investigated in this study. Material and methods. CK-160 cervical carcinoma xenografts were used as preclinical tumor model. A total of 43 tumors were included in the study, and of these tumors, 17 were used to search for correlations between the stromal and physiologic microenvironments, 11 were subjected to DCE-MRI, and 15 were subjected to DW-MRI. DCE-MRI and DW-MRI were carried out at 1.5 T with a clinical MR scanner and a slotted tube resonator transceiver coil constructed for mice. Fraction of connective tissue (CTFCol) and fraction of hypoxic tissue (HFPim) were determined by immunohistochemistry. A Millar SPC 320 catheter was used to measure tumor interstitial fluid pressure (IFP). Results. CTFCol showed a positive correlation to IFP and an inverse correlation to HFPim. The apparent diffusion coefficient assessed by DW-MRI was inversely correlated to CTFCol, whereas no correlation was found between DCE-MRI-derived parameters and CTFCol. Conclusion. DW-MRI is a potentially useful method for characterizing the stromal microenvironment of tumors.

Systematic bias in genomic classification due to contaminating non-neoplastic tissue in breast tumor samples.

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Elloumi, Fathi; Hu, Zhiyuan; Li, Yan; Parker, Joel S; Gulley, Margaret L; Amos, Keith D; Troester, Melissa A

2011-06-30

Genomic tests are available to predict breast cancer recurrence and to guide clinical decision making. These predictors provide recurrence risk scores along with a measure of uncertainty, usually a confidence interval. The confidence interval conveys random error and not systematic bias. Standard tumor sampling methods make this problematic, as it is common to have a substantial proportion (typically 30-50%) of a tumor sample comprised of histologically benign tissue. This "normal" tissue could represent a source of non-random error or systematic bias in genomic classification. To assess the performance characteristics of genomic classification to systematic error from normal contamination, we collected 55 tumor samples and paired tumor-adjacent normal tissue. Using genomic signatures from the tumor and paired normal, we evaluated how increasing normal contamination altered recurrence risk scores for various genomic predictors. Simulations of normal tissue contamination caused misclassification of tumors in all predictors evaluated, but different breast cancer predictors showed different types of vulnerability to normal tissue bias. While two predictors had unpredictable direction of bias (either higher or lower risk of relapse resulted from normal contamination), one signature showed predictable direction of normal tissue effects. Due to this predictable direction of effect, this signature (the PAM50) was adjusted for normal tissue contamination and these corrections improved sensitivity and negative predictive value. For all three assays quality control standards and/or appropriate bias adjustment strategies can be used to improve assay reliability. Normal tissue sampled concurrently with tumor is an important source of bias in breast genomic predictors. All genomic predictors show some sensitivity to normal tissue contamination and ideal strategies for mitigating this bias vary depending upon the particular genes and computational methods used in the predictor.

The microcapsule-type formaldehyde scavenger: the preparation and the application in urea-formaldehyde adhesives.

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Duan, Hongyun; Qiu, Teng; Guo, Longhai; Ye, Jun; Li, Xiaoyu

2015-08-15

The limitation and regulation of formaldehyde emissions (FE) now shows great importance in wood-based materials such as plywood and particle board manufactured for building and furnishing materials. The widely used formaldehyde-based adhesives are one of the main sources of FE from the wood products. In this work, a new kind of long-term effective formaldehyde scavenger in the microcapsule form was prepared by using an intra-liquid desiccation method. The characterizations of the capsule (UC) were performed including the morphologies, the yields, the loading efficiency as well as its sustained-release of urea in aqueous conditions. The prepared UC could be integrated in urea-formaldehyde resins by simply physical blending, and the mixtures were available to be applied as the adhesives for the manufacture of plywood. The bonding strength (BS) and the FE of the bonded plywood in both short (3h) and long (12 week) period were evaluated in detail. It was found that the FE profile of the plywood behaved following a duple exponential law within 12 week. The addition of UC in the adhesive can effectively depress the FE of the plywood not only in a short period after preparation but also in a long-term period during its practical application. The slow released urea would continuously suppress the emission of toxic formaldehyde in a sustained manner without obviously deteriorating on the BS of the adhesives. Copyright © 2015 Elsevier B.V. All rights reserved.

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

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Kündig, Pascale; Giesen, Charlotte; Jackson, Hartland; Bodenmiller, Bernd; Papassotirolopus, Bärbel; Freiberger, Sandra Nicole; Aquino, Catharine; Opitz, Lennart; Varga, Zsuzsanna

2018-05-08

Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas. We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis. No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas. Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the

Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

International Nuclear Information System (INIS)

Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S.

2006-01-01

In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents

Radionuclide investigation of the blood flow in tumor and normal rat tissues in induced hyperglycemia

International Nuclear Information System (INIS)

Istomin, Yu.P.; Shitikov, B.D.; Markova, L.V.

1991-01-01

Radionuclide angiography was performed in rats with transplantable tumors. Induced hyperglycemia was shown to result in blood flow inhibition in tumor and normal tissues of tumor-bearing rats. Some differences were revealed in a degree of reversibility of blood flow disorders in tissues of the above strains. The results obtained confirmed the advisability of radiation therapy at the height of a decrease in tumor blood

White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

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Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

2010-01-01

The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

International Nuclear Information System (INIS)

Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

2013-01-01

Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

Mandibular phosphaturic mesenchymal tumor-mixed connective tissue variant in a young girl.

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Luo, Lisa; Low, Nelson; Vandervord, John

2013-11-01

Phosphaturic mesenchymal tumor-mixed connective tissue variant (PMTMCT) is an extremely rare tumor associated with tumor-induced osteomalacia. The majority occur in middle age and arise from the extremities. This report describes a young girl with PMTMCT arising in the mandible and with no evidence of paraneoplastic syndrome.

Magnetic resonance of lipomatous, fibrous and muscular tissue tumors

International Nuclear Information System (INIS)

Dippolito, G.; Balzarini, L.; Patrillo, R.; Tess, J.T.; Musumeci, R.

1991-01-01

Two hundred and three MR examinations were reviewed of 195 patients with lipomatous, fibrous and muscular tissues tumors which were evaluated at staging or during the follow-up. All examinations were obtained with a 1.5 T superconductive magnet, and both T 1 and T 2 -weighted images were acquired. Its high contrast resolution, its direct multiplanarity and its allowing both T 1 and T 2 -weighted images to be obtained are the mos important characteristics of MR imaging. In our experience, MRI demonstrated a high overall accuracy (94.8%) - 94.1% at restaging alone - with similar sensitivity both at the staging of the disease (97.5%) and during the follow-up (96%). Overall sensibility was 96.3%. MR specificity in histologically proven relapses was 86.8%. Even though it is gradually assessing itself as the most important method in the evaluation of soft tissues masses, MRI allows an histological diagnosis to be made only in lipomatous tumors and in benign fibrous tumors due to their specific signal features. The commonest though specific finding is a soft tissue mass with relatively low signal intensity in T 1 -weighted images. In our opinion, MR imaging is the method of choice during the follow-up of the disease, whereas it is probably a complementary technique in the staging. (author)

Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

Science.gov (United States)

Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

2014-01-01

Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

Functional evaluation of bone marrow derived DC of tumor bearing mice after immunotherapy

International Nuclear Information System (INIS)

Li Min; Chen Cheng; Gu Tao; Zhou Huan; Zhang Feng; Zhu Yibei; Yu Gehua; Zhang Xueguang; Gu Zongjiang

2006-01-01

Objective: To evaluate the function of bone marrow derived DC of tumor bearing mice after immunotherapy. Methods: Tumor bearing mice were immunized with DC vaccine plus injection of agonistic anti-4-1BB monoclonal antibody. The proliferation of T cells primed with bone marrow derived DC of tumor bearing mice after immunotherapy was tested by 3 H-TdR incorporation. ELISA was employed to determine the levels of IL-2, IFN-γ and IL-10 secreted by DC primed T cells. Results: Bone marrow derived DC of tumor bearing mice was less efficient in stimulating the proliferation of T cells and IL-2 and IFN-γ secretion made by T cells. After immunotherapy, the proliferation of cells and IL-2 and IFN-γ secretionmade by T cells were enhanced. Conclusion: The function of bone marrow derived DC of tumor bearing mice after immunotherapy was ameliorated. (authors)

MR muscle tractography study on VX2 soft-tissue tumor in rabbits

International Nuclear Information System (INIS)

Li Yonggang; Guo Liang; Xie Daohai; Hu Chunhogn; Guo Maofeng; Zhu Wei; Chen Jianhua; Xing Jianming; Wang Renfa

2008-01-01

Objective: To determine if diffusion tensor imaging (DTI) and muscle fiber tracts of muscle disease are feasible. Methods: Twenty Newzealand white rabbits were implanted with 0.2 ml VX 2 tumor tissue suspension in the right proximal thighs. MRI and DTI were performed on these rabbits and DTI of muscle fiber tracts in the muscles around the lesions were reconstructed. The fractional anisotropy(FA) and volume ratio anisotropy(VrA) of the tumor and the normal muscle were analyzed. The correlation study between MRI and pathological findings was done. Results: All experimental animal models of rabbit VX 2 soft tissue tumors were successfully established. The difference of FA between the central parenchyma area and the necrosis area, the peripheral area of the tumor, the adjacent and contralateral normal muscle was statistically significant (P 0.05). The difference of FA and VrA between the adjacent and contralateral normal muscle was not statistically significant (P>0.05). The arrangement of normal muscle was regular on DTI of muscle tract. The muscle around the tumor lesions was infiltrated and destructed, which demonstrated irregular and interrupted muscle fiber on muscle tractography. Conclusion: DTI is advantageous to demonstrate the structure of soft tissue tumors and its border, which should be helpful in the structure and function research of muscle, as well as in the diagnosis of muscle diseases. (authors)

Biodegradation of formaldehyde from contaminated air using a laboratory scale static-bed bioreactor

Directory of Open Access Journals (Sweden)

Yaghoub Hajizadeh

2014-01-01

Full Text Available Aims: The objective of the present study was to evaluate the performance of an aerobic fixed-bed bioreactor (FBR enriched with microorganisms of sewage sludge in biodegradation of formaldehyde in air stream with various retention times and airflow rates in laboratory scale. Materials and Methods: An aerobic biofilter 60 cm in height and 14 cm internal diameter made of steel was constructed and packed with a mixture of pumice and compost as a medium and utilized in this study. The microorganism′s growth, which is derived from the sludge of a municipal wastewater treatment plant, was initiated by adding nutrient. During the first few days of run, the airflow containing different concentrations of formaldehyde (from 24 ± 3 to 224 ± 5 mg/m 3 was introduced to the reactor to ensure biological adaptation. Sampling was performed through a series of two impingers containing adsorbent, and analyzed by chromotropic acid assay using DR-5000. Results: The maximum removal and elimination capacity of formaldehyde was yielded at 0.48 ± 0.06 g/m 3 /h inlet loading rate and 180 s of empty bed retention time (EBRT. These values for stabilized days were almost 88% and 0.42 g/m 3 /h, respectively. Conclusion: The results showed that by increasing the inlet concentration of formaldehyde and reducing the EBRT, the formaldehyde removal capacity of the system decreases. Aerobic bioreactor with appropriate bed volume and compatible with inlet pollutant mass flow rate in optimum retention time will admissibly degrade and reduce the formaldehyde concentration from contaminated gas phase, such as gases produced in municipal wastewater treatment facilities.

Quantification of atmospheric formaldehyde by infrared absorption spectroscopy

Science.gov (United States)

Hoffnagle, John; Fleck, Derek; Rella, Chris; Kim-Hak, David

2017-04-01

Formaldehyde is a toxic, carcinogenic compound that can contaminate ambient air as a result of combustion or outgassing of commercial products such as adhesives used to fabricate plywood and to affix indoor carpeting. Like many small molecules, formaldehyde has an infrared absorption spectrum exhibiting bands of ro-vibrational transitions that are well resolved at low pressure and therefore well suited for optical analysis of formaldehyde concentration. We describe progress in applying cavity ring-down spectroscopy of the 2v5 band (the first overtone of the asymmetric C-H stretch, origin at 1770 nm) to the quantitative analysis of formaldehyde concentration in ambient air. Preliminary results suggest that a sensitivity of 1-2 ppb in a measurement interval of a few seconds, and 0.1-0.2 ppb in a few minutes, should be achievable with a compact, robust, and field-deployable instrument. Finally, we note that recent satellites monitoring snapshots of formaldehyde columns give insights into global formaldehyde production, migration and lifetime. The ability to monitor formaldehyde with a small and portable analyzer has the potential to aid in validation of these snapshots and to provide complementary data to show vertical dispersions with high spatial accuracy.

Tumor control and normal tissue toxicity: The two faces of radiotherapy

NARCIS (Netherlands)

van Oorschot, B.

2016-01-01

This thesis discusses the two contrasting sides of radiotherapy: tumor control and normal tissue toxicity. On one hand, radiation treatment aims to target the tumor with the highest possible radiation dose, inducing as much lethal DNA damage as possible. On the other hand however, escalation of the

Pediatric brain tumors of neuroepithelial tissue; Hirntumoren des neuroepithelialen Gewebes im Kindesalter

Energy Technology Data Exchange (ETDEWEB)

Papanagiotou, P.; Politi, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany); Bergmann, M. [Klinikum Bremen-Mitte, Institut fuer Klinische Neuropathologie, Bremen (Germany); Pekrun, A. [Klinikum Bremen-Mitte, Klinik fuer Kinder- und Jugendmedizin, paed. Haematologie/Onkologie, Neonatologie, Bremen (Germany); Juergens, K.U. [Klinikum Bremen-Mitte, ZEMODI-Zentrum fuer moderne Diagnostik, MRT, Nuklearmedizin und PET-CT, Bremen (Germany)

2014-08-15

Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [German] Tumoren des neuroepithelialen Gewebes stellen die mit Abstand groesste Gruppe der paediatrischen Hirntumoren dar und werden je nach deren Ursprung in diversen Subtypen unterteilt. Das Neuropil beinhaltet diverse Subtypen von Gliazellen: Astrozyten, Oligodendrozyten, ependymale Zellen und modifizierte ependymale Zellen, die den Plexus choroideus formen. In diesem Review werden die bildgebenden Aspekte mittels CT und MRT der haeufigsten Tumoren des neuroepithelialen Gewebes diskutiert. (orig.)

[Familial retinoblastoma: cytogenetic study of the tumor].

Science.gov (United States)

Robledo Batanero, M; Manzanal Martínez, A; Ayuso García, C; Benítez Ortiz, J

1990-05-01

We report a case of familiar retinoblastoma, in which both mother and daughter show bilateral retinoblastoma. The cytogenetic study, in both peripheral blood lymphocytes and tumoral tissue did not show alterations on the 13 chromosome, although we found a complex kariotype in tumoral tissue defined by three celular lines. In all of them appears a marker in which the 6 chromosome is involved (der 6). The derivated of 6 chromosome are markers highly characteristic of the retinoblastoma cases, and can be related with the aggressivity of tumor and the appearance of the second tumors.

Formaldehyde as a carbon and electron shuttle between autotroph and heterotroph populations in acidic hydrothermal vents of Norris Geyser Basin, Yellowstone National Park

Energy Technology Data Exchange (ETDEWEB)

Moran, James J.; Whitmore, Laura M.; Isern, Nancy G.; Romine, Margaret F.; Riha, Krystin M.; Inskeep, William P.; Kreuzer, Helen W.

2016-03-19

The Norris Geyser Basin in Yellowstone National Park contains a large number of hydrothermal systems, which host microbial populations supported by primary productivity associated with a suite of chemolithotrophic metabolisms. We demonstrate that Metallosphaera yellowstonesis MK1, a facultative autotrophic archaeon isolated from a hyperthermal acidic hydrous ferric oxide (HFO) spring in Norris Geyser Basin, excretes formaldehyde during autotrophic growth. To determine the fate of formaldehyde in this low organic carbon environment, we incubated native microbial mat (containing M. yellowstonensis) from a HFO spring with 13C-formaldehyde. Isotopic analysis of incubation-derived CO2 and biomass showed that formaldehyde was both oxidized and assimilated by members of the community. Autotrophy, formaldehyde oxidation, and formaldehyde assimilation displayed different sensitivities to chemical inhibitors, suggesting that distinct sub-populations in the mat selectively perform these functions. Our results demonstrate that electrons originally resulting from iron oxidation can energetically fuel autotrophic carbon fixation and associated formaldehyde excretion, and that formaldehyde is both oxidized and assimilated by different organisms within the native microbial community. Thus, formaldehyde can effectively act as a carbon and electron shuttle connecting the autotrophic, iron oxidizing members with associated heterotrophic members in the HFO community.

Hardness evaluation of cured urea-formaldehyde resins with different formaldehyde/urea mole ratios using nanoindentation method

Science.gov (United States)

Byung-Dae Park; Charles R. Frihart; Yan Yu; Adya P. Singh

2013-01-01

To understand the influence of formaldehyde/urea (F/U) mole ratio on the properties of urea–formaldehyde (UF) resins, this study investigated hardness of cured UF resins with different F/U mole ratios using a nanoindentation method. The traditional Brinell hardness (HB) method was also used...

PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models

NARCIS (Netherlands)

Meehan, Terrence F.; Conte, Nathalie; Goldstein, Theodore; Inghirami, Giorgio; Murakami, Mark A.; Brabetz, Sebastian; Gu, Zhiping; Wiser, Jeffrey A.; Dunn, Patrick; Begley, Dale A.; Krupke, Debra M.; Bertotti, Andrea; Bruna, Alejandra; Brush, Matthew H.; Byrne, Annette T.; Caldas, Carlos; Christie, Amanda L.; Clark, Dominic A.; Dowst, Heidi; Dry, Jonathan R.; Doroshow, James H.; Duchamp, Olivier; Evrard, Yvonne A.; Ferretti, Stephane; Frese, Kristopher K.; Goodwin, Neal C.; Greenawalt, Danielle; Haendel, Melissa A.; Hermans, Els; Houghton, Peter J.; Jonkers, Jos; Kemper, Kristel; Khor, Tin O.; Lewis, Michael T.; Lloyd, K. C. Kent; Mason, Jeremy; Medico, Enzo; Neuhauser, Steven B.; Olson, James M.; Peeper, Daniel S.; Rueda, Oscar M.; Seong, Je Kyung; Trusolino, Livio; Vinolo, Emilie; Wechsler-Reya, Robert J.; Weinstock, David M.; Welm, Alana; Weroha, S. John; Amant, Frédéric; Pfister, Stefan M.; Kool, Marcel; Parkinson, Helen; Butte, Atul J.; Bult, Carol J.

2017-01-01

Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models

Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

Science.gov (United States)

Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

2011-01-01

Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulations vary among different neoplastic models. Thus, it is thought that the type and quantities of inflammatory mediators generated during neoplasia dictate the composition of the resultant MDSC response. Although much interest has been devoted to monocytic MDSC biology, a fundamental gap remains in our understanding of the derivation of granulocytic MDSC. In settings of heightened granulocytic MDSC responses, we hypothesized that inappropriate production of G-CSF is a key initiator of granulocytic MDSC accumulation. We observed abundant amounts of G-CSF in vivo, which correlated with robust granulocytic MDSC responses in multiple tumor models. Using G-CSF loss- and gain-of-function approaches, we demonstrated for the first time that: 1) abrogating G-CSF production significantly diminished granulocytic MDSC accumulation and tumor growth; 2) ectopically over-expressing G-CSF in G-CSF-negative tumors significantly augmented granulocytic MDSC accumulation and tumor growth; and 3) treatment of naïve healthy mice with recombinant G-CSF protein elicited granulocytic-like MDSC remarkably similar to those induced under tumor-bearing conditions. Collectively, we demonstrated that tumor-derived G-CSF enhances tumor growth through granulocytic MDSC-dependent mechanisms. These findings provide us with novel insights into MDSC subset development and potentially new biomarkers or targets for cancer therapy. PMID:22110722

Myxoid Neurothekeoma: A Rare Soft Tissue Tumor of Hand in a ...

African Journals Online (AJOL)

Nerve sheath myxoma (neurothekeoma) is an uncommon benign soft tissue tumor of the peripheral nerves with fairly distinctive histological features. It is commonly located on the upper extremities or the head and the neck.[1] Histologic variants of neurothekeoma include myxoid, cellular, and mixed tumors. A recent ...

Soft tissue tumors occurring in the perinatal/infancy setting: 1st part

Directory of Open Access Journals (Sweden)

Gavino Faa

2018-02-01

Full Text Available Soft tissue sarcomas represent an important chapter of pediatric oncology, accounting for about 10% of all malignancies in childhood. The aim of this work is to summarize the clinical, histological, immunohistochemical and genetic features of the most frequent soft tissue tumors presenting in infants and in young subjects before the age of 10. For each entity, the most relevant data regarding prognosis and treatment will be summarized, and the most important morphological and immunohistochemical features will be reported. The most frequent myofibroblastic tumors, fatty tumors and skeletal muscle tumors occurring in infancy and adolescence will be described in this first part. The aim of this work, mainly based on a practical approach, is to help perinatal and pediatric pathologists in the diagnosis of a group of tumors that are diagnostically challenging, due to their rarity, the contemporary expression of multiple immunohistochemical markers and frequent lack of known genetic abnormalities.

Intracranial phosphaturic mesenchymal tumor, mixed connective tissue variant presenting without oncogenic osteomalacia.

Science.gov (United States)

Bower, Regina S; Daugherty, Wilson P; Giannini, Caterina; Parney, Ian F

2012-01-01

Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) is a rare tumor typically occurring in soft tissues and bone, causing oncogenic (tumor-induced) osteomalacia (TIO) through secretion of the phosphaturic hormone, fibroblast growth factor-23 (FGF-23). Rare tumors identical to PMTMCT occur without known TIO. Intracranial localization of PMTMCT is extremely rare, with only two cases reported in the literature. We present a very unusual case of a patient with an intracranial PMTMCT that presented with neurologic changes without osteomalacia. A 67-year-old woman presented with progressive incontinence, apathy, and abulia after having undergone a total knee replacement 1 month earlier. Imaging disclosed a large left frontal anterior fossa mass. She underwent uncomplicated surgical resection of this tumor. Surprisingly, histopathology suggested PMTMCT. Reverse transcription polymerase chain reaction (RT-PCR) assay demonstrating FGF-23 expression in the tumor confirmed the diagnosis. Serum FGF-23 levels postoperatively were normal and she had no clinical or laboratory evidence of osteomalacia or phosphaturia. This report should serve to alert clinicians to the possibility that PMTMCT can be included in the differential diagnosis of intracranial masses even in the absence of tumor-induced osteomalacia.

Prevalence, extension and characteristics of fluid-fluid levels in bone and soft tissue tumors

Energy Technology Data Exchange (ETDEWEB)

Dyck, P. van; Venstermans, C.; Gielen, J.; Parizel, P.M. [University Hospital Antwerp, Department of Radiology, Edegem (Belgium); Vanhoenacker, F.M. [University Hospital Antwerp, Department of Radiology, Edegem (Belgium); AZ St-Maarten, Department of Radiology, Duffel/Mechelen (Belgium); Vogel, J. [Leiden University Medical Centre, Department of Orthopedics, Leiden (Netherlands); Kroon, H.M.; Bloem, J.L. [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Schepper, A.M.A. de [University Hospital Antwerp, Department of Radiology, Edegem (Belgium); Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands)

2006-12-15

The purpose of this study was to determine the prevalence, extension and signal characteristics of fluid-fluid levels in a large series of 700 bone and 700 soft tissue tumors. Out of a multi-institutional database, MRI of 700 consecutive patients with a bone tumor and MRI of 700 consecutive patients with a soft tissue neoplasm were retrospectively reviewed for the presence of fluid-fluid levels. Extension (single, multiple and proportion of the lesion occupied by fluid-fluid levels) and signal characteristics on magnetic resonance imaging of fluid-fluid levels were determined. In all patients, pathologic correlation was available. Of 700 patients with a bone tumor, 19 (10 male and 9 female; mean age, 29 years) presented with a fluid-fluid level (prevalence 2.7%). Multiple fluid-fluid levels occupying at least one half of the total volume of the lesion were found in the majority of patients. Diagnoses included aneurysmal bone cyst (ten cases), fibrous dysplasia (two cases), osteoblastoma (one case), simple bone cyst (one case), telangiectatic osteosarcoma (one case), ''brown tumor'' (one case), chondroblastoma (one case) and giant cell tumor (two cases). Of 700 patients with a soft tissue tumor, 20 (9 males and 11 females; mean age, 34 years) presented with a fluid-fluid level (prevalence 2.9%). Multiple fluid-fluid levels occupying at least one half of the total volume of the lesion were found in the majority of patients. Diagnoses included cavernous hemangioma (12 cases), synovial sarcoma (3 cases), angiosarcoma (1 case), aneurysmal bone cyst of soft tissue (1 case), myxofibrosarcoma (1 case) and high-grade sarcoma ''not otherwise specified'' (2 cases). In our series, the largest reported in the literature to the best of our knowledge, the presence of fluid-fluid levels is a rare finding with a prevalence of 2.7 and 2.9% in bone and soft tissue tumors, respectively. Fluid-fluid levels remain a non-specific finding and can

Bone and soft tissue tumors of hip and pelvis

Energy Technology Data Exchange (ETDEWEB)

Bloem, Johan L., E-mail: j.l.bloem@lumc.nl [Leiden University Medical Center, Department of Radiology, PO Box 9600, 2300 RC Leiden (Netherlands); Reidsma, Inge I., E-mail: i.i.reidsma@lumc.nl [Leiden University Medical Center, Department of Radiology, PO Box 9600, 2300 RC Leiden (Netherlands)

2012-12-15

Objective is to identify epidemiologic and radiologic criteria allowing specific diagnoses of tumors and tumor-like lesions in the hip region and pelvis, and to optimize pre-operative staging. Patients with pelvic tumors are usually older, and their tumors are larger relative to patients with tumors in extremities. The majority of tumors in the pelvis are malignant (metastases, myeloma, chondrosarcoma, Ewing-, osteo-, and MFH/fibrosarcoma), while those in the proximal femur are in majority benign (fibrous dysplasia, solitary bone cyst, and osteoid osteoma). Soft tissue masses in the thigh in the elderly are typically sarcomas without tumor specific signs. Common tumor-like lesions occurring in the hip and pelvis that can mimic neoplasm are: infections (including tuberculosis), insufficiency/avulsion fractures, cysts, fibrous dysplasia, aneurysmal bone cyst, Langerhans cell histiocytosis, and Paget's disease. Local MR staging is based on the compartmental anatomy. The psoas and gluteal muscles are easily invaded by sarcoma originating in the ileum. The pectineus muscle protects the neurovascular bundle at the level of the hip. The thigh is separated into three compartments, some structures (Sartorius muscle) cross borders between compartments. Immobile joints (SI-joints, osteoarthritic hip) are relatively easily crossed by sarcoma and giant cell tumor.

Malignant phosphaturic mesenchymal tumor, mixed connective tissue variant of the tongue

OpenAIRE

Uramoto, Naoki; Furukawa, Mitsuru; Yoshizaki, Tomokazu

2008-01-01

The majority of the oncogenic osteomalacia-associated mesenchymal tumors are considered to belong to the category of phosphaturic mesenchymal tumors, mixed connective tissue (PMTMCT) variant, of which malignant cases are very rare. Here we report a case of a recurrent malignant PMTMCT variant which arose in the tongue. The patient was treated with surgery at an initial treatment and the first recurrence. In accordance with the tumor recurrence and resection, the hypophosphatemia progressed an...

Changes in regional blood flow of normal and tumor tissues following hyperthermia and combined X-ray irradiation

International Nuclear Information System (INIS)

Suga, Kazuyoshi

1986-01-01

Hyperthermia and X-ray irradiation were given to Ehrlich tumors, which were induced in the ventrum of the right hind foot of ICR mice, and to the normal tissues. Their effects on regional blood flow were examined using Xe-133 local clearance method. Blood flow of the normal tissues remained unchanged by heating at 41 deg C for 30 minutes, and increased by heating at 43 deg C and 45 deg C for 30 minutes. On the contrary, blood flow of the tumors decreased with an increase in temperature. When hypertermia (43 deg C for 30 minutes) was combined with irradiation of 30 Gy, decrease in blood flow of the tumors was greater than the normal tissues at 24 hours. Blood flow of the tumors depended on tumor size. The decreased amount of blood flow by hyperthermia was more for tumors > 250 mm 3 than tumors 3 . Blood flow ratios of tumor to normal tissues were also smaller in tumors > 250 mm 3 than tumors 3 . In the case of tumors 3 , blood flow tended to return to normal at 3 hr after heating at 43 deg C for 30 min. However, this was not seen in tumors > 250 mm 3 . (Namekawa, K.)

Photochemical decomposition of Formaldehyde in solution

International Nuclear Information System (INIS)

Garrido Z, G.

1995-01-01

In this work was studied the effect of ultraviolet radiation produced by a mercury low pressure lamp in solutions of formaldehyde. These solutions were exposed to ultraviolet rays at different times. In some of these series of solutions was added a photosensibilizer in order to obtain a high photodecomposition of formaldehyde. The techniques used for determine the products of the decomposition were the following: 1. In order to measure the residual formaldehyde and glioxal, the Hantzsch and 2,4-dinitrophenylhydrazine methods were used. 2. pH's measurements of the solutions, before and after exposition. 3. Paper's chromatography for determine presence of formed acids. 4. Acid-base tritiations for measure total acidification. We observed that when the time of exposition to UV rays was increased, a high photodecomposition of formaldehyde was formed and, besides, a greater quantity of another products. Of the reagents used like photosensibilizers, with the ruthenium reagent, the best results were obtained. (Author)

Quality management and accreditation of research tissue banks: experience of the National Center for Tumor Diseases (NCT) Heidelberg.

Science.gov (United States)

Herpel, Esther; Röcken, Christoph; Manke, Heike; Schirmacher, Peter; Flechtenmacher, Christa

2010-12-01

Tissue banks are key resource and technology platforms in biomedical research that address the molecular pathogenesis of diseases as well as disease prevention, diagnosis, and treatment. Due to the central role of tissue banks in standardized collection, storage, and distribution of human tissues and their derivatives, quality management and its external assessment is becoming increasingly relevant for the maintenance, acceptance, and funding of tissue banks. Little experience exists regarding formalized external evaluation of tissue banks, especially regarding certification and accreditation. Based on the accreditation of the National Center of Tumor Diseases (NCT) tissue bank in Heidelberg (Germany), criteria, requirements, processes, and implications were compiled and evaluated. Accreditation formally approved professional competence and performance of the tissue bank in all steps involved in tissue collection, storage, handling as well as macroscopic and histologic examination and final (exit) examination of the tissue and transfer supervised by board-certified competent histopathologists. Thereby, accreditation provides a comprehensive measure to evaluate and document the quality standard of tissue research banks and may play a significant role in the future assessment of tissue banks. Furthermore, accreditation may support harmonization and standardization of tissue banking for biomedical research purposes.

Bimodal activated carbons derived from resorcinol-formaldehyde cryogels

Science.gov (United States)

Szczurek, Andrzej; Amaral-Labat, Gisele; Fierro, Vanessa; Pizzi, Antonio; Celzard, Alain

2011-01-01

Resorcinol-formaldehyde cryogels prepared at different dilution ratios have been activated with phosphoric acid at 450 °C and compared with their carbonaceous counterparts obtained by pyrolysis at 900 °C. Whereas the latter were, as expected, highly mesoporous carbons, the former cryogels had very different pore textures. Highly diluted cryogels allowed preparation of microporous materials with high surface areas, but activation of initially dense cryogels led to almost non-porous carbons, with much lower surface areas than those obtained by pyrolysis. The optimal acid concentration for activation, corresponding to stoichiometry between molecules of acid and hydroxyl groups, was 2 M l−1, and the acid–cryogel contact time also had an optimal value. Such optimization allowed us to achieve surface areas and micropore volumes among the highest ever obtained by activation with H3PO4, close to 2200 m2 g−1 and 0.7 cm3 g−1, respectively. Activation of diluted cryogels with a lower acid concentration of 1.2 M l−1 led to authentic bimodal activated carbons, having a surface area as high as 1780 m2 g−1 and 0.6 cm3 g−1 of microporous volume easily accessible through a widely developed macroporosity. PMID:27877405

Bimodal activated carbons derived from resorcinol-formaldehyde cryogels

Energy Technology Data Exchange (ETDEWEB)

Szczurek, Andrzej; Amaral-Labat, Gisele; Fierro, Vanessa; Celzard, Alain [Institut Jean Lamour-UMR CNRS 7198, CNRS-Nancy-Universite-UPV-Metz, Departement Chimie et Physique des Solides et des Surfaces. ENSTIB, 27 rue Philippe Seguin, BP 1041, 88051 Epinal cedex 9 (France); Pizzi, Antonio, E-mail: Alain.Celzard@enstib.uhp-nancy.fr [ENSTIB-LERMAB, Nancy-Universite, 27 rue Philippe Seguin, BP1041, 88051 Epinal cedex 9 (France)

2011-06-15

Resorcinol-formaldehyde cryogels prepared at different dilution ratios have been activated with phosphoric acid at 450 deg. C and compared with their carbonaceous counterparts obtained by pyrolysis at 900 deg. C. Whereas the latter were, as expected, highly mesoporous carbons, the former cryogels had very different pore textures. Highly diluted cryogels allowed preparation of microporous materials with high surface areas, but activation of initially dense cryogels led to almost non-porous carbons, with much lower surface areas than those obtained by pyrolysis. The optimal acid concentration for activation, corresponding to stoichiometry between molecules of acid and hydroxyl groups, was 2 M l{sup -1}, and the acid-cryogel contact time also had an optimal value. Such optimization allowed us to achieve surface areas and micropore volumes among the highest ever obtained by activation with H{sub 3}PO{sub 4}, close to 2200 m{sup 2} g{sup -1} and 0.7 cm{sup 3} g{sup -1}, respectively. Activation of diluted cryogels with a lower acid concentration of 1.2 M l{sup -1} led to authentic bimodal activated carbons, having a surface area as high as 1780 m{sup 2} g{sup -1} and 0.6 cm{sup 3} g{sup -1} of microporous volume easily accessible through a widely developed macroporosity.

Interleukin 33 in tumor microenvironment is crucial for the accumulation and function of myeloid-derived suppressor cells

Science.gov (United States)

Xiao, Peng; Wan, Xiaopeng; Cui, Bijun; Liu, Yang; Qiu, Chenyang; Rong, Jiabing; Zheng, Mingzhu; Song, Yinjing; Chen, Luoquan; He, Jia; Tan, Qinchun; Wang, Xiaojia; Shao, Xiying; Liu, Yuhua; Cao, Xuetao; Wang, Qingqing

2016-01-01

ABSTRACT Tumor-induced, myeloid-derived suppressor cells (MDSCs)-mediated immune dysfunction is an important mechanism that leads to tumor immune escape and the inefficacy of cancer immunotherapy. Importantly, tumor-infiltrating MDSCs have much stronger ability compared to MDSCs in the periphery. However, the mechanisms that tumor microenvironment induces the accumulation and function of MDSCs are poorly understood. Here, we report that Interleukin-33 (IL-33) – a cytokine which can be abundantly released in tumor tissues both in 4T1-bearing mice and breast cancer patients, is crucial for facilitating the expansion of MDSCs. IL-33 in tumor microenvironment reduces the apoptosis and sustains the survival of MDSCs through induction of autocrine secretion of GM-CSF, which forms a positive amplifying loop for MDSC accumulation. This is in conjunction with IL-33-driven induction of arginase-1 expression and activation of NF-κB and MAPK signaling in MDSCs which augments their immunosuppressive ability, and histone modifications were involved in IL-33 signaling in MDSCs. In ST2−/− mice, the defect of IL-33 signaling in MDSCs attenuates the immunosuppressive and pro-tumoral capacity of MDSCs. Our results identify IL-33 as a critical mediator that contributes to the abnormal expansion and enhanced immunosuppressive function of MDSCs within tumor microenvironment, which can be potentially targeted to reverse MDSC-mediated tumor immune evasion. PMID:26942079

Human adipose tissue-derived mesenchymal stem cells inhibit T-cell lymphoma growth in vitro and in vivo.

Science.gov (United States)

Ahn, Jin-Ok; Chae, Ji-Sang; Coh, Ye-Rin; Jung, Woo-Sung; Lee, Hee-Woo; Shin, Il-Seob; Kang, Sung-Keun; Youn, Hwa-Young

2014-09-01

Human mesenchymal stem cells (hMSCs) are thought to be one of the most reliable stem cell sources for a variety of cell therapies. This study investigated the anti-tumor effect of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on EL4 murine T-cell lymphoma in vitro and in vivo. The growth-inhibitory effect of hAT-MSCs on EL4 tumor cells was evaluated using a WST-1 cell proliferation assay. Cell-cycle arrest and apoptosis were investigated by flow cytometry and western blot. To evaluate an anti-tumor effect of hAT-MSCs on T-cell lymphoma in vivo, CM-DiI-labeled hAT-MSCs were circumtumorally injected in tumor-bearing nude mice, and tumor size was measured. hAT-MSCs inhibited T-cell lymphoma growth by altering cell-cycle progression and inducing apoptosis in vitro. hAT-MSCs inhibited tumor growth in tumor-bearing nude mice and prolonged survival time. Immunofluorescence analysis showed that hAT-MSCs migrated to tumor sites. hAT-MSCs suppress the growth of T-cell lymphoma, suggesting a therapeutic option for T-cell lymphoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Tumor tissue levels of tissue inhibitor of metalloproteinases-I (TIMP-I) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients

DEFF Research Database (Denmark)

Schrohl, Anne-Sofie; Look, Maxime P.; Gelder, Marion E. Meijer-van

2009-01-01

BACKGROUND: We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome...... an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy. Our...... after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. METHODS: From our original retrospectively collected tumor samples we...

Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

International Nuclear Information System (INIS)

Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

2012-01-01

Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

Comparison of the effect between an active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue and that using irradiated tumor cells

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji; Yamamoto, Yoichi; Morita, Masaru

1983-01-01

The effect of the active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was compared with that of irradiated (10,000 rads) tumor cells on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 6th day, irradiation with a dose of 3,000 rads was performed. On the 14th day, tumor cells and concomitant mononuclear cells which were separated from the low-dose irradiated tumor tissue (2,000 rads on the 6th day) were injected into the left hind paws of one group of the tumor-bearing mice. On the same day, irradiated MM46 tumor cells were injected into the left hind paws of another group of the tumor-bearing mice. Effectiveness of these two methods of active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. The active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was far more effective than irradiated tumor cells on this tumor system involved. (author)

Correlation between diagnostic capability of MR-mammography and histology of tissue adjacent to tumor

Energy Technology Data Exchange (ETDEWEB)

Takahara, Taro [St. Marianna Univ., Kawasaki, Kanagawa (Japan)

1996-12-01

The purpose of this paper is to evaluate correlation between the capability in the diagnosis of tumor extent and histology of adjacent tissue. MR-mammography (MRM) was obtained in twenty-one patients with surgically resected breast cancer by 0.5 T superconducting magnet (PHILIPS GY-ROSCAN T5-II, release 3.1). Pre and postcontrast 3D-spoiled gradient echo sequence were employed for MRM with spectral presaturation with inversion recovery (SPIR) and on-resonance MTC. The contrast determination time, the passing time of the center of k-space, was 1 min 50 s in 14 cases with key-hole imaging, and 2 min 46 s in 7 cases without key-hole imaging. Early enhancing area was considered as a tumor and an accuracy of tumor extent was evaluated by two radiologists. Accurate interpretation was obtained in 9 of 9 cases with atrophic mammary gland with fatty replacement and 3 of 3 cases with severe fibrosis in mammary gland. Seven cases were unclear in tumor margin due to intense enhancement of the adjacent tissue. One of 3 cases with normal mammary gland showed unclear margin of the tumor, which corresponded to the area of rich population of lobules in a young patient. Two of 2 cases of fibrocystic change with nonproliferative lesions in one case and proliferative lesions without atypia in another, showed unclear margin of tumor. Two cases of 2 intraductal spreading and 2 of 2 cases of massive interstitial invasion also showed unclear margin. The accuracy of tumor extent was found to have no correlation with either histology or enhancing ratio of the tumor. In conclusion, it is warranted to say that histology of adjacent tissue is an important factor to determine diagnostic capability of tumor extent by MRM. Fat replacement and fibrosis of the surrounding tissue are main causes of clear visualization of tumor, while normal mammary gland in young patients, fibrocystic change, intraductal spreading and invasion lead to the unclearness of tumor margin. (author)

Correlation between diagnostic capability of MR-mammography and histology of tissue adjacent to tumor

International Nuclear Information System (INIS)

Takahara, Taro

1996-01-01

The purpose of this paper is to evaluate correlation between the capability in the diagnosis of tumor extent and histology of adjacent tissue. MR-mammography (MRM) was obtained in twenty-one patients with surgically resected breast cancer by 0.5 T superconducting magnet (PHILIPS GY-ROSCAN T5-II, release 3.1). Pre and postcontrast 3D-spoiled gradient echo sequence were employed for MRM with spectral presaturation with inversion recovery (SPIR) and on-resonance MTC. The contrast determination time, the passing time of the center of k-space, was 1 min 50 s in 14 cases with key-hole imaging, and 2 min 46 s in 7 cases without key-hole imaging. Early enhancing area was considered as a tumor and an accuracy of tumor extent was evaluated by two radiologists. Accurate interpretation was obtained in 9 of 9 cases with atrophic mammary gland with fatty replacement and 3 of 3 cases with severe fibrosis in mammary gland. Seven cases were unclear in tumor margin due to intense enhancement of the adjacent tissue. One of 3 cases with normal mammary gland showed unclear margin of the tumor, which corresponded to the area of rich population of lobules in a young patient. Two of 2 cases of fibrocystic change with nonproliferative lesions in one case and proliferative lesions without atypia in another, showed unclear margin of tumor. Two cases of 2 intraductal spreading and 2 of 2 cases of massive interstitial invasion also showed unclear margin. The accuracy of tumor extent was found to have no correlation with either histology or enhancing ratio of the tumor. In conclusion, it is warranted to say that histology of adjacent tissue is an important factor to determine diagnostic capability of tumor extent by MRM. Fat replacement and fibrosis of the surrounding tissue are main causes of clear visualization of tumor, while normal mammary gland in young patients, fibrocystic change, intraductal spreading and invasion lead to the unclearness of tumor margin. (author)

Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening.

Science.gov (United States)

Fong, Eliza L S; Martinez, Mariane; Yang, Jun; Mikos, Antonios G; Navone, Nora M; Harrington, Daniel A; Farach-Carson, Mary C

2014-07-07

The lack of effective therapies for bone metastatic prostate cancer (PCa) underscores the need for accurate models of the disease to enable the discovery of new therapeutic targets and to test drug sensitivities of individual tumors. To this end, the patient-derived xenograft (PDX) PCa model using immunocompromised mice was established to model the disease with greater fidelity than is possible with currently employed cell lines grown on tissue culture plastic. However, poorly adherent PDX tumor cells exhibit low viability in standard culture, making it difficult to manipulate these cells for subsequent controlled mechanistic studies. To overcome this challenge, we encapsulated PDX tumor cells within a three-dimensional hyaluronan-based hydrogel and demonstrated that the hydrogel maintains PDX cell viability with continued native androgen receptor expression. Furthermore, a differential sensitivity to docetaxel, a chemotherapeutic drug, was observed as compared to a traditional PCa cell line. These findings underscore the potential impact of this novel 3D PDX PCa model as a diagnostic platform for rapid drug evaluation and ultimately push personalized medicine toward clinical reality.

Some growth factors in neoplastic tissues of brain tumors of different histological structure

Directory of Open Access Journals (Sweden)

O. I. Kit

2016-01-01

Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

Tissue-specific regulation of mouse MicroRNA genes in endoderm-derived tissues

OpenAIRE

Gao, Yan; Schug, Jonathan; McKenna, Lindsay B.; Le Lay, John; Kaestner, Klaus H.; Greenbaum, Linda E.

2010-01-01

MicroRNAs fine-tune the activity of hundreds of protein-coding genes. The identification of tissue-specific microRNAs and their promoters has been constrained by the limited sensitivity of prior microRNA quantification methods. Here, we determine the entire microRNAome of three endoderm-derived tissues, liver, jejunum and pancreas, using ultra-high throughput sequencing. Although many microRNA genes are expressed at comparable levels, 162 microRNAs exhibited striking tissue-specificity. After...

High-level expression of podoplanin in benign and malignant soft tissue tumors: immunohistochemical and quantitative real-time RT-PCR analysis.

Science.gov (United States)

Xu, Yongjun; Ogose, Akira; Kawashima, Hiroyuki; Hotta, Tetsuo; Ariizumi, Takashi; Li, Guidong; Umezu, Hajime; Endo, Naoto

2011-03-01

Podoplanin is a 38 kDa mucin-type transmembrane glycoprotein that was first identified in rat glomerular epithelial cells (podocytes). It is expressed in normal lymphatic endothelium, but is absent from vascular endothelial cells. D2-40 is a commercially available mouse monoclonal antibody which binds to an epitope on human podoplanin. D2-40 immunoreactivity is therefore highly sensitive and specific for lymphatic endothelium. Recent investigations have shown widespread applications of immunohistochemical staining with D2-40 in evaluating podoplanin expression as an immunohistochemical marker for diagnosis and prognosis in various tumors. To determine whether the podoplanin (D2-40) antibody may be useful for the diagnosis of soft tissue tumors, 125 cases, including 4 kinds of benign tumors, 15 kinds of malignant tumors and 3 kinds of tumor-like lesions were immunostained using the D2-40 antibody. Total RNA was extracted from frozen tumor tissue obtained from 41 corresponding soft tissue tumor patients and 12 kinds of soft tissue tumor cell lines. Quantitative real-time PCR reactions were performed. Immunohistochemical and quantitative real-time RT-PCR analyses demonstrated the expression of the podoplanin protein and mRNA in the majority of benign and malignant soft tissue tumors and tumor-like lesions examined, with the exception of alveolar soft part sarcoma, embryonal and alveolar rhabdomyosarcoma, extraskeletal Ewing's sarcoma/peripheral primitive neuro-ectodermal tumor and lipoma, which were completely negative for podoplanin. Since it is widely and highly expressed in nearly all kinds of soft tissue tumors, especially in spindle cell sarcoma, myxoid type soft tissue tumors and soft tissue tumors of the nervous system, podoplanin is considered to have little value in the differential diagnosis of soft tissue tumors.

Current advances in mathematical modeling of anti-cancer drug penetration into tumor tissues.

Science.gov (United States)

Kim, Munju; Gillies, Robert J; Rejniak, Katarzyna A

2013-11-18

Delivery of anti-cancer drugs to tumor tissues, including their interstitial transport and cellular uptake, is a complex process involving various biochemical, mechanical, and biophysical factors. Mathematical modeling provides a means through which to understand this complexity better, as well as to examine interactions between contributing components in a systematic way via computational simulations and quantitative analyses. In this review, we present the current state of mathematical modeling approaches that address phenomena related to drug delivery. We describe how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules. Finally, we discuss how integration of mathematical modeling with experimental or clinical data can provide better tools to understand the drug delivery process, in particular to examine the specific tissue- or compound-related factors that limit drug penetration through tumors. Such tools will be important in designing new chemotherapy targets and optimal treatment strategies, as well as in developing non-invasive diagnosis to monitor treatment response and detect tumor recurrence.

Degradation of formaldehyde in anaerobic sequencing batch biofilm reactor (ASBBR)

Energy Technology Data Exchange (ETDEWEB)

Pereira, N.S. [Laboratorio de Processos Biologicos (LPB), Departamento de Hidraulica e Saneamento, Escola de Engenharia de Sao Carlos (EESC), Universidade de Sao Paulo - USP, Engenharia Ambiental, Bloco 4-F, Av. Joao Dagnone, 1100 Santa Angelina, 13.563-120 Sao Carlos, SP (Brazil); Zaiat, M. [Laboratorio de Processos Biologicos (LPB), Departamento de Hidraulica e Saneamento, Escola de Engenharia de Sao Carlos (EESC), Universidade de Sao Paulo - USP, Engenharia Ambiental, Bloco 4-F, Av. Joao Dagnone, 1100 Santa Angelina, 13.563-120 Sao Carlos, SP (Brazil)], E-mail: zaiat@sc.usp.br

2009-04-30

The present study evaluated the degradation of formaldehyde in a bench-scale anaerobic sequencing batch reactor, which contained biomass immobilized in polyurethane foam matrices. The reactor was operated for 212 days at 35 deg. C with 8 h sequential cycles, under different affluent formaldehyde concentrations ranging from 31.6 to 1104.4 mg/L (formaldehyde loading rates from 0.08 to 2.78 kg/m{sup 3} day). The results indicate excellent reactor stability and over 99% efficiency in formaldehyde removal, with average effluent formaldehyde concentration of 3.6 {+-} 1.7 mg/L. Formaldehyde degradation rates increased from 204.9 to 698.3 mg/L h as the initial concentration of formaldehyde was increased from around 100 to around 1100 mg/L. However, accumulation of organic matter was observed in the effluent (chemical oxygen demand (COD) values above 500 mg/L) due to the presence of non-degraded organic acids, especially acetic and propionic acids. This observation poses an important question regarding the anaerobic route of formaldehyde degradation, which might differ substantially from that reported in the literature. The anaerobic degradation pathway can be associated with the formation of long-chain oligomers from formaldehyde. Such long- or short-chain polymers are probably the precursors of organic acid formation by means of acidogenic anaerobic microorganisms.

Degradation of formaldehyde in anaerobic sequencing batch biofilm reactor (ASBBR)

International Nuclear Information System (INIS)

Pereira, N.S.; Zaiat, M.

2009-01-01

The present study evaluated the degradation of formaldehyde in a bench-scale anaerobic sequencing batch reactor, which contained biomass immobilized in polyurethane foam matrices. The reactor was operated for 212 days at 35 deg. C with 8 h sequential cycles, under different affluent formaldehyde concentrations ranging from 31.6 to 1104.4 mg/L (formaldehyde loading rates from 0.08 to 2.78 kg/m 3 day). The results indicate excellent reactor stability and over 99% efficiency in formaldehyde removal, with average effluent formaldehyde concentration of 3.6 ± 1.7 mg/L. Formaldehyde degradation rates increased from 204.9 to 698.3 mg/L h as the initial concentration of formaldehyde was increased from around 100 to around 1100 mg/L. However, accumulation of organic matter was observed in the effluent (chemical oxygen demand (COD) values above 500 mg/L) due to the presence of non-degraded organic acids, especially acetic and propionic acids. This observation poses an important question regarding the anaerobic route of formaldehyde degradation, which might differ substantially from that reported in the literature. The anaerobic degradation pathway can be associated with the formation of long-chain oligomers from formaldehyde. Such long- or short-chain polymers are probably the precursors of organic acid formation by means of acidogenic anaerobic microorganisms

Apoptotic Tumor Cell-Derived Extracellular Vesicles as Important Regulators of the Onco-Regenerative Niche

Directory of Open Access Journals (Sweden)

Christopher D. Gregory

2018-05-01

Full Text Available Cells undergoing apoptosis produce heterogeneous populations of membrane delimited extracellular vesicles (Apo-EVs which vary not only in size—from tens of nanometers to several microns—but also in molecular composition and cargo. Apo-EVs carry a variety of potentially biologically active components, including small molecules, proteins, and nucleic acids. Larger forms of Apo-EVs, commonly termed “apoptotic bodies,” can carry organelles, such as mitochondria and nuclear fragments. Molecules displayed on the surface of extracellular vesicles (EVs can contribute substantially to their size, as well as their functions. Thus far, relatively little is known of the functional significance of Apo-EVs apart from their roles in fragmentation of dying cells and indicated immunomodulatory activities. Here, we discuss EV production by dying tumor cells and consider the possible roles of Apo-EVs in a cell death-driven sector of the tumor microenvironment known as the onco-regenerative niche (ORN. We propose that tumor-derived Apo-EVs are significant vehicles of the ORN, functioning as critical intercellular communicators that activate oncogenic tissue repair and regeneration pathways. We highlight important outstanding questions and suggest that Apo-EVs may harbor novel therapeutic targets.

A biomimetic tumor tissue phantom for validating diffusion-weighted MRI measurements.

Science.gov (United States)

McHugh, Damien J; Zhou, Feng-Lei; Wimpenny, Ian; Poologasundarampillai, Gowsihan; Naish, Josephine H; Hubbard Cristinacce, Penny L; Parker, Geoffrey J M

2018-07-01

To develop a biomimetic tumor tissue phantom which more closely reflects water diffusion in biological tissue than previously used phantoms, and to evaluate the stability of the phantom and its potential as a tool for validating diffusion-weighted (DW) MRI measurements. Coaxial-electrospraying was used to generate micron-sized hollow polymer spheres, which mimic cells. The bulk structure was immersed in water, providing a DW-MRI phantom whose apparent diffusion coefficient (ADC) and microstructural properties were evaluated over a period of 10 months. Independent characterization of the phantom's microstructure was performed using scanning electron microscopy (SEM). The repeatability of the construction process was investigated by generating a second phantom, which underwent high resolution synchrotron-CT as well as SEM and MR scans. ADC values were stable (coefficients of variation (CoVs) < 5%), and varied with diffusion time, with average values of 1.44 ± 0.03 µm 2 /ms (Δ = 12 ms) and 1.20 ± 0.05 µm 2 /ms (Δ = 45 ms). Microstructural parameters showed greater variability (CoVs up to 13%), with evidence of bias in sphere size estimates. Similar trends were observed in the second phantom. A novel biomimetic phantom has been developed and shown to be stable over 10 months. It is envisaged that such phantoms will be used for further investigation of microstructural models relevant to characterizing tumor tissue, and may also find application in evaluating acquisition protocols and comparing DW-MRI-derived biomarkers obtained from different scanners at different sites. Magn Reson Med 80:147-158, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is

Analysis of formalin-fixed, paraffin-embedded (FFPE) tissue via proteomic techniques and misconceptions of antigen retrieval.

Science.gov (United States)

O'Rourke, Matthew B; Padula, Matthew P

2016-01-01

Since emerging in the late 19(th) century, formaldehyde fixation has become a standard method for preservation of tissues from clinical samples. The advantage of formaldehyde fixation is that fixed tissues can be stored at room temperature for decades without concern for degradation. This has led to the generation of huge tissue banks containing thousands of clinically significant samples. Here we review techniques for proteomic analysis of formalin-fixed, paraffin-embedded (FFPE) tissue samples with a specific focus on the methods used to extract and break formaldehyde crosslinks. We also discuss an error-of-interpretation associated with the technique known as "antigen retrieval." We have discovered that this term has been mistakenly applied to two disparate molecular techniques; therefore, we argue that a terminology change is needed to ensure accurate reporting of experimental results. Finally, we suggest that more investigation is required to fully understand the process of formaldehyde fixation and its subsequent reversal.

Influence of low-energy laser radiation on normal skin and certain tumor tissues

Energy Technology Data Exchange (ETDEWEB)

Pletnev, S.D.; Karpenko, O.M.

For some years, the authors' Institute has studied the influence of various types of low-energy laser radiation on normal tissue and the growth of tumors. Radiation at 3 and 30 J/cm/sup 2/ causes an increase in biological activity of various cell elements, manifested as an increase in mitotic activity of the cells in the basal layer of the epidermis, conglomeration of chromatin in the cell nuclei and an increase in degranulation of fat cells in the process of their migration to the reticular layer. Also noted was an increase in content of fibroblastic and lymphohistocytic elements in the dermis, as well as an increase in collagenization of connective tissue. It was found that irradiation of the skin by helium-neon, cadmium-helium and nitrogen lasers before and after grafting of the cells of various tumors modifies the course of the tumor process. This effect is apparently related to the fact that systematic irradiation results in changes creating a favorable background for survival and proliferation of tumor cells in the skin tissue medium. The changes facilitate an increase in survival and growth of both pigmented and nonpigmented tumors. Low power radiation stimulates the activity of the cells or cell structures; medium power stimulates their activity; high power suppresses activity.

7746 CONCENTRATIONS OF FORMALDEHYDE IN RAIN WATERS ...

African Journals Online (AJOL)

Win7Ent

2013-06-03

Jun 3, 2013 ... The chromotropic acid method described by the. National Institute for ... concentration range of the formaldehyde in the rain waters varied from month to month throughout the six ... vicinity of vegetation [3]. Formaldehyde is the ...

Mechanic effect of pulsed focused ultrasound in tumor and muscle tissue evaluated by MRI, histology, and microarray analysis

International Nuclear Information System (INIS)

Hundt, Walter; Yuh, Esther L.; Steinbach, Silke; Bednarski, Mark D.; Guccione, Samira

2010-01-01

The purpose of this study was to investigate the effect of pulsed high-intensity focused ultrasound (HIFU) to tumor and muscle tissue. Pulsed HIFU was applied to tumor and muscle tissue in C3H/Km mice. Three hours after HIFU treatment pre- and post-contrast T1-wt, T2-wt images and a diffusion-wt STEAM-sequence were obtained. After MR imaging, the animals were euthenized and the treated tumor and muscle was taken out for histology and functional genomic analysis. In the tumor tissue a slight increase of the diffusion coefficient could be found. In the muscle tissue T2 images showed increased signal intensity and post-contrast T1 showed a decreased contrast uptake in the center and a severe contrast uptake in the surrounding muscle tissue. A significant increase of the diffusion coefficient was found. Gene expression analysis revealed profound changes in the expression levels of 29 genes being up-regulated and 3 genes being down-regulated in the muscle tissue and 31 genes being up-regulated and 15 genes being down-regulated in the SCCVII tumor tissue. Seven genes were up-regulated in both tissue types. The highest up-regulated gene in the tumor and muscle tissue encoded for Mouse histone H2A.1 gene (FC = 13.2 ± 20.6) and Apolipoprotein E (FC = 12.8 ± 27.4) respectively MHC class III (FC = 83.7 ± 67.4) and hsp70 (FC = 75.3 ± 85.0). Immunoblot confirmed the presence of HSP70 protein in the muscle tissue. Pulsed HIFU treatment on tumor and muscle tissue results in dramatic changes in gene expression, indicating that the effect of pulsed HIFU is in some regard dependent and also independent of the tissue type.

Pre-operative radiotherapy in soft tissue tumors: Assessment of response by static post-contrast MR imaging compared to histopathology

International Nuclear Information System (INIS)

Einarsdottir, H.; Wejde, J.; Bauer, H.C.F.

2000-01-01

To evaluate if static post-contrast MR imaging was adequate to assess tumor viability after pre-operative radiotherapy in soft tissue sarcoma. Post-contrast MR imaging of 36 soft tissue sarcomas performed 0 - 54 days (median 13 days) after pre-operative radiotherapy, were retrospectively reviewed and compared to post-operative histopathology reports. The contrast enhancement of the tumor was visually graded as minor, moderate or extensive. From the post-operative histopathology reports, three types of tumor response to radiotherapy were defined: Poor, intermediate or good. The size of the tumors before and after radiation was compared. Even if most viable tumors enhanced more than non-viable tumors, there was major overlapping and significant contrast enhancement could be seen in tumors where histopathological examination revealed no viable tumor tissue. Based on histopathology, there were 12 good responders; 8 of these showed minor, 3 moderate and 1 extensive contrast enhancement on MR imaging. Sixteen tumors had an intermediate response; 3 showed minor, 8 moderate and 5 extensive enhancement. Eight tumors had poor response; none showed minor enhancement, 3 moderate and 5 extensive enhancement. Both increase and Decrease in tumor size was seen in lesions with a good therapy response. Static post-contrast MR imaging cannot reliably assess tumor viability after pre-operative radiotherapy in soft tissue sarcoma. In tumors with no viable tumor tissue, moderate and extensive contrast enhancement can be seen

Effect of a mouse mammary tumor virus-derived protein vaccine on primary tumor development in mice

NARCIS (Netherlands)

Creemers, P.; Ouwehand, J.; Bentveizen, P.

1978-01-01

The vaccines used in this study were derived from purified murine mammary tumor virus (MuMTV) preparations. Approximately 60% of the protein fractions consisted of the major viral membrane glycoprotein gp52. Inoculation sc of 10 pg MuMTV-S-derived vaccine significantly delayed the appearance of

A cytogenetic analysis of 2 cases of phosphaturic mesenchymal tumor of mixed connective tissue type.

Science.gov (United States)

Graham, Rondell P; Hodge, Jennelle C; Folpe, Andrew L; Oliveira, Andre M; Meyer, Kevin J; Jenkins, Robert B; Sim, Franklin H; Sukov, William R

2012-08-01

Phosphaturic mesenchymal tumor of mixed connective tissue type is a rare, histologically distinctive mesenchymal neoplasm associated with tumor-induced osteomalacia resulting from production of the phosphaturic hormone fibroblast growth factor 23. Because of its rarity, specific genetic alterations that contribute to the pathogenesis of these tumors have yet to be elucidated. Herein, we report the abnormal karyotypes from 2 cases of confirmed phosphaturic mesenchymal tumor of mixed connective tissue type. G-banded analysis demonstrated the first tumor to have a karyotype of 46,Y,t(X;3;14)(q13;p25;q21)[15]/46XY[5], and the second tumor to have a karyotype of 46, XY,add(2)(q31),add(4)(q31.1)[2]/92,slx2[3]/46,sl,der(2)t(2;4)(q14.2;p14),der(4)t(2;4)(q14.2;p14),add(4)(q31.1)[10]/46,sdl,add(13)(q34)[4]/92,sdl2x2[1]. These represent what is, to our knowledge, the first examples of abnormal karyotypes obtained from phosphaturic mesenchymal tumor of mixed connective tissue type. Copyright © 2012 Elsevier Inc. All rights reserved.

Formaldehyde in Alcoholic Beverages: Large Chemical Survey Using Purpald Screening Followed by Chromotropic Acid Spectrophotometry with Multivariate Curve Resolution

Directory of Open Access Journals (Sweden)

Julien A. Jendral

2011-01-01

Full Text Available A strategy for analyzing formaldehyde in beer, wine, spirits, and unrecorded alcohol was developed, and 508 samples from worldwide origin were analyzed. In the first step, samples are qualitatively screened using a simple colorimetric test with the purpald reagent, which is extremely sensitive for formaldehyde (detection limit 0.1 mg/L. 210 samples (41% gave a positive purpald reaction. In the second step, formaldehyde in positive samples is confirmed by quantitative spectrophotometry of the chromotropic acid-formaldehyde derivative combined with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS. Calculation of UV-VIS and 13C NMR spectra confirmed the monocationic dibenzoxanthylium structure as the product of the reaction and disproved the widely cited para,para-quinoidal structure. Method validation for the spectrophotometric procedure showed a detection limit of 0.09 mg/L and a precision of 4.2–8.2% CV. In total, 132 samples (26% contained formaldehyde with an average of 0.27 mg/L (range 0–14.4 mg/L. The highest incidence occurred in tequila (83%, Asian spirits (59%, grape marc (54%, and brandy (50%. Our survey showed that only 9 samples (1.8% had formaldehyde levels above the WHO IPCS tolerable concentration of 2.6 mg/L.

Formaldehyde in alcoholic beverages: large chemical survey using purpald screening followed by chromotropic Acid spectrophotometry with multivariate curve resolution.

Science.gov (United States)

Jendral, Julien A; Monakhova, Yulia B; Lachenmeier, Dirk W

2011-01-01

A strategy for analyzing formaldehyde in beer, wine, spirits, and unrecorded alcohol was developed, and 508 samples from worldwide origin were analyzed. In the first step, samples are qualitatively screened using a simple colorimetric test with the purpald reagent, which is extremely sensitive for formaldehyde (detection limit 0.1 mg/L). 210 samples (41%) gave a positive purpald reaction. In the second step, formaldehyde in positive samples is confirmed by quantitative spectrophotometry of the chromotropic acid-formaldehyde derivative combined with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). Calculation of UV-VIS and (13)C NMR spectra confirmed the monocationic dibenzoxanthylium structure as the product of the reaction and disproved the widely cited para,para-quinoidal structure. Method validation for the spectrophotometric procedure showed a detection limit of 0.09 mg/L and a precision of 4.2-8.2% CV. In total, 132 samples (26%) contained formaldehyde with an average of 0.27 mg/L (range 0-14.4 mg/L). The highest incidence occurred in tequila (83%), Asian spirits (59%), grape marc (54%), and brandy (50%). Our survey showed that only 9 samples (1.8%) had formaldehyde levels above the WHO IPCS tolerable concentration of 2.6 mg/L.

Formaldehyde as an antiseptic in the production of alcohol from molasses

Energy Technology Data Exchange (ETDEWEB)

Rosa, M; Vernerova, J; Stros, F

1962-01-01

The effect of formaldehyde as an antiseptic for the noncontaminated alcohol fermentation of molasses was examined with five different yeast-mash batches containing formaldehyde 0.01%. Following 24 hour cultivation, increase in the activity of formaldehyde-inoculated mash was lowered by 47%; the formaldehyde decreased the alcohol fermentation and lessened the rate of fermentation of sugar by 20% in noncontaminated mash. The decrease in the fermentation rate was also observed during the entire course of fermentation. On the other hand, formaldehyde addition to molasses contaminated with lactic acid bacteria accelerated the fermentation rate by inhibiting the bacterial growth; the degree of retardation due to the contamination was greater than that due to the antiseptic. The view that formaldehyde decreased the effectiveness of growth substances by binding the amino acid present in mash mixtures could not be confirmed; it was believed that formaldehyde was absorbed by yeast cells even through the entities thus destroyed could not be differentiated from living cells by methylene blue. Higher resistance of yeast cultures to formaldehyde was obtained by repeated transfers of the yeast in media containing formaldehyde. It was concluded that formaldehyde added to contaminated molasses inhibited the further growth of the contamination, increased yield of ethanol on the basis of the sugar, and simultaneously decreased the net yield of ethanol in contrast to the yield from noncontaminated mashes in the absence of formaldehyde.

Assessment of lipid peroxidation and p53 as a biomarker of carcinogenesis among workers exposed to formaldehyde in the cosmetic industry.

Science.gov (United States)

Attia, Dalia; Mansour, Neveen; Taha, Fatma; Seif El Dein, Aisha

2016-06-01

Despite the wide use of cosmetic products, they exert a number of health effects on tissues ranging from irritation to cancer. Our study aimed at assessing the effect of formaldehyde on lipid peroxidation and verifying the susceptibility to carcinogenesis using p53 as a biomarker among workers exposed to formaldehyde in cosmetic industry. Our entire exposed group (n = 40) and the controls (n = 20) were subjected to estimation of formate in urine, serum malondialdehyde (MDA), and p53. Also, complete blood picture, liver, and kidney function tests were carried out. The study revealed significant increase in the levels of formate, MDA, and p53 in the exposed group compared with their control group. Our results showed that workers in cosmetic industry had significant exposure to formaldehyde. Furthermore, the study pointed to the negative impact of formaldehyde as a cause of oxidative stress and suspicious carcinogen. © The Author(s) 2014.

Mass Spectrometry Imaging for the Classification of Tumor Tissue

NARCIS (Netherlands)

Mascini, N.E.

2016-01-01

Mass spectrometry imaging (MSI) can detect and identify many different molecules without the need for labeling. In addition, it can provide their spatial distributions as ‘molecular maps’. These features make MSI well suited for studying the molecular makeup of tumor tissue. Currently, there is an

Visual Analytics for the Exploration of Tumor Tissue Characterization

DEFF Research Database (Denmark)

Raidou, R. G.; Van Der Heide, U. A.; Dinh, C. V.

2015-01-01

imaging data, to derive per voxel a number of features, indicative of tissue properties. However, the high dimensionality and complexity of this imaging-derived feature space is prohibiting for easy exploration and analysis - especially when clinical researchers require to associate observations from...... the feature space to other reference data, e.g., features derived from histopathological data. Currently, the exploratory approach used in clinical research consists of juxtaposing these data, visually comparing them and mentally reconstructing their relationships. This is a time consuming and tedious process......, from which it is difficult to obtain the required insight. We propose a visual tool for: (1) easy exploration and visual analysis of the feature space of imaging-derived tissue characteristics and (2) knowledge discovery and hypothesis generation and confirmation, with respect to reference data used...

Amide proton transfer imaging of high intensity focused ultrasound-treated tumor tissue

NARCIS (Netherlands)

Hectors, S.J.C.G.; Jacobs, I.; Strijkers, G.J.; Nicolay, K.

2014-01-01

Purpose: In this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. Methods: APT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

Amide Proton Transfer Imaging of High Intensity Focused Ultrasound-Treated Tumor Tissue

NARCIS (Netherlands)

Hectors, Stefanie J. C. G.; Jacobs, Igor; Strijkers, Gustav J.; Nicolay, Klaas

2014-01-01

PurposeIn this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. MethodsAPT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

[Determination of formaldehyde and acetaldehyde in packaging paper by dansylhydrazine derivatization-high performance liquid chromatography-fluorescence detection].

Science.gov (United States)

Gong, Shuguo; Liang, Yong; Tang, Liyun; Huang, Ping; Dai, Yunhui

2017-07-08

A high performance liquid chromatography with fluorescence detection (HPLC-FLD) method was developed for the simultaneous determination of formaldehyde and acetaldehyde in packaging paper by dansylhydrazine (DNSH) derivatization. The samples were extracted by derivatization reagent for 30 min, and derived for 24 h. After purifying treatment with a PSA/C18 cartridge, a Diamonsil ® C18 column (150 mm×4.6 mm, 5 μ m) was used as stationary phase for separation, the mixtures of acetic acid aqueous solution (pH 2.55)-acetonitrile were used as mobile phases by gradient elution, and the excitation and emission wavelengths were 330 nm and 484 nm, respectively. The results showed that the recoveries of formaldehyde and acetaldehyde spiked in the samples were 81.64%-106.78%, and the relative standard deviations (RSDs) were 2.02%-5.53% ( n =5). The limits of detection of formaldehyde and acetaldehyde were 19.2 μ g/kg and 20.7 μ g/kg, respectively. The limits of quantification of formaldehyde and acetaldehyde were 63.9 μ g/kg and 69.1 μ g/kg, respectively. The method is simple, sensitive and reproducible. It provides a basic approach for the determination of trace formaldehyde and acetaldehyde.

DNER, an epigenetically modulated gene, regulates glioblastoma-derived neurosphere cell differentiation and tumor propagation.

Science.gov (United States)

Sun, Peng; Xia, Shuli; Lal, Bachchu; Eberhart, Charles G; Quinones-Hinojosa, Alfredo; Maciaczyk, Jarek; Matsui, William; Dimeco, Francesco; Piccirillo, Sara M; Vescovi, Angelo L; Laterra, John

2009-07-01

Neurospheres derived from glioblastoma (GBM) and other solid malignancies contain neoplastic stem-like cells that efficiently propagate tumor growth and resist cytotoxic therapeutics. The primary objective of this study was to use histone-modifying agents to elucidate mechanisms by which the phenotype and tumor-promoting capacity of GBM-derived neoplastic stem-like cells are regulated. Using established GBM-derived neurosphere lines and low passage primary GBM-derived neurospheres, we show that histone deacetylase (HDAC) inhibitors inhibit growth, induce differentiation, and induce apoptosis of neoplastic neurosphere cells. A specific gene product induced by HDAC inhibition, Delta/Notch-like epidermal growth factor-related receptor (DNER), inhibited the growth of GBM-derived neurospheres, induced their differentiation in vivo and in vitro, and inhibited their engraftment and growth as tumor xenografts. The differentiating and tumor suppressive effects of DNER, a noncanonical Notch ligand, contrast with the previously established tumor-promoting effects of canonical Notch signaling in brain cancer stem-like cells. Our findings are the first to implicate noncanonical Notch signaling in the regulation of neoplastic stem-like cells and suggest novel neoplastic stem cell targeting treatment strategies for GBM and potentially other solid malignancies.

Spectral Clustering Predicts Tumor Tissue Heterogeneity Using Dynamic 18F-FDG PET: A Complement to the Standard Compartmental Modeling Approach.

Science.gov (United States)

Katiyar, Prateek; Divine, Mathew R; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Schölkopf, Bernhard; Pichler, Bernd J; Disselhorst, Jonathan A

2017-04-01

In this study, we described and validated an unsupervised segmentation algorithm for the assessment of tumor heterogeneity using dynamic 18 F-FDG PET. The aim of our study was to objectively evaluate the proposed method and make comparisons with compartmental modeling parametric maps and SUV segmentations using simulations of clinically relevant tumor tissue types. Methods: An irreversible 2-tissue-compartmental model was implemented to simulate clinical and preclinical 18 F-FDG PET time-activity curves using population-based arterial input functions (80 clinical and 12 preclinical) and the kinetic parameter values of 3 tumor tissue types. The simulated time-activity curves were corrupted with different levels of noise and used to calculate the tissue-type misclassification errors of spectral clustering (SC), parametric maps, and SUV segmentation. The utility of the inverse noise variance- and Laplacian score-derived frame weighting schemes before SC was also investigated. Finally, the SC scheme with the best results was tested on a dynamic 18 F-FDG measurement of a mouse bearing subcutaneous colon cancer and validated using histology. Results: In the preclinical setup, the inverse noise variance-weighted SC exhibited the lowest misclassification errors (8.09%-28.53%) at all noise levels in contrast to the Laplacian score-weighted SC (16.12%-31.23%), unweighted SC (25.73%-40.03%), parametric maps (28.02%-61.45%), and SUV (45.49%-45.63%) segmentation. The classification efficacy of both weighted SC schemes in the clinical case was comparable to the unweighted SC. When applied to the dynamic 18 F-FDG measurement of colon cancer, the proposed algorithm accurately identified densely vascularized regions from the rest of the tumor. In addition, the segmented regions and clusterwise average time-activity curves showed excellent correlation with the tumor histology. Conclusion: The promising results of SC mark its position as a robust tool for quantification of tumor

Primary Formation Path of Formaldehyde in Hydrothermal Vents

Science.gov (United States)

Inaba, Satoshi

2018-03-01

Formaldehyde is abundant in the universe and one of the fundamental molecules for life. Hydrothermal vents produce a substantial amount of hydrogen molecules by serpentinization and promote reductive reactions of single carbon compounds. The abundance of formaldehyde is expected to be low due to the high Gibbs free energy in hydrothermal vents. We consider two competing formation pathways of formaldehyde: (1) the reduction of CO by H2 and (2) the reduction of HCOOH by H2 to form a methanediol, followed by the dehydration of the methanediol. We performed a number of quantum chemical simulations to examine the formation of formaldehyde in the gas phase as well as in aqueous solution. The energy barrier is significantly reduced by the catalytic effect of water molecules in aqueous solution and becomes lowest when a water cluster consisted of 5 water molecules catalyzes the reduction. The energy barrier to form a methanediol by the reduction of HCOOH is lower by 17.5 kcal/mol than that to form a formaldehyde by the reduction of CO. Considering the low energy barrier to dehydrate methanediol, the primary pathway to form formaldehyde in hydrothermal vents is concluded to be the reduction of HCOOH by H2, followed by the dehydration of methanediol.

Development of melamine modified urea formaldehyde resins based o nstrong acidic pH catalyzed urea formaldehyde polymer

Science.gov (United States)

Chung-Yun Hse

2009-01-01

To upgrade the performance of urea-formaldehyde (UF) resin bonded particleboards, melamine modified urea-formaldehyde (MUF) resins based on strong acidic pH catalyzed UF polymers were investigated. The study was conducted in a series of two experiments: 1) formulation of MUF resins based on a UF polymer catalyzed with strong acidic pH and 2) determination of the...

Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

Science.gov (United States)

Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

2017-09-01

Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

A Catalytic Role for Proangiogenic Marrow-Derived Cells in Tumor Neovascularization

Science.gov (United States)

Seandel, Marco; Butler, Jason; Lyden, David; Rafii, Shahin

2010-01-01

Small numbers of proangiogenic bone marrow-derived cells (BMDCs) can play pivotal roles in tumor progression. In this issue of Cancer Cell, two papers, utilizing different tumor angiogenesis models, both find that activated MMP-9 delivered by BMDCs modulates neovessel remodeling, thereby promoting tumor growth. The changes in microvascular anatomy induced by MMP-9-expressing BMDCs are strikingly different between the preirradiated tumor vascular bed model employed by Ahn and Brown and the invasive glioblastoma model utilized by Du et al., likely mirroring the complexity of the real tumor microenvironment and the intricacy of roles of different BMDC populations in mediating tumor neoangiogenesis. PMID:18328420

the histological effects of formaldehyde vapour on the lungs

African Journals Online (AJOL)

Uwaifoh

2012-12-31

Dec 31, 2012 ... In the world day, the active chemical used for embalming is formaldehyde. ... formaldehyde causes nasopharyngeal cancer in humans,” (Collins et al., 1997; Gardner et ... pattern for inhalation of formaldehyde in rats presented cell ... temperature of about 25-28oC and photo-periodicity of 12h day/ 12h night.

Development of a formaldehyde biosensor with application to synthetic methylotrophy.

Science.gov (United States)

Woolston, Benjamin M; Roth, Timothy; Kohale, Ishwar; Liu, David R; Stephanopoulos, Gregory

2018-01-01

Formaldehyde is a prevalent environmental toxin and a key intermediate in single carbon metabolism. The ability to monitor formaldehyde concentration is, therefore, of interest for both environmental monitoring and for metabolic engineering of native and synthetic methylotrophs, but current methods suffer from low sensitivity, complex workflows, or require expensive analytical equipment. Here we develop a formaldehyde biosensor based on the FrmR repressor protein and cognate promoter of Escherichia coli. Optimization of the native repressor binding site and regulatory architecture enabled detection at levels as low as 1 µM. We then used the sensor to benchmark the in vivo activity of several NAD-dependent methanol dehydrogenase (Mdh) variants, the rate-limiting enzyme that catalyzes the first step of methanol assimilation. In order to use this biosensor to distinguish individuals in a mixed population of Mdh variants, we developed a strategy to prevent cross-talk by using glutathione as a formaldehyde sink to minimize intercellular formaldehyde diffusion. Finally, we applied this biosensor to balance expression of mdh and the formaldehyde assimilation enzymes hps and phi in an engineered E. coli strain to minimize formaldehyde build-up while also reducing the burden of heterologous expression. This biosensor offers a quick and simple method for sensitively detecting formaldehyde, and has the potential to be used as the basis for directed evolution of Mdh and dynamic formaldehyde control strategies for establishing synthetic methylotrophy. © 2017 Wiley Periodicals, Inc.

MicroRNAs in the Tumor Biology of Soft Tissue Sarcomas

NARCIS (Netherlands)

C.M.M. Gits (Caroline)

2013-01-01

markdownabstract__Abstract__ Soft tissue sarcomas represent a rare, heterogeneous group of mesenchymal tumors. In sarcomas, histological classification, prediction of clinical behaviour and prognosis, and targeted treatment is often a challenge. A better understanding of the biology of soft

Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.

Science.gov (United States)

Garcia, Emmanuel; Becker, Veronika G C; McCullough, Danielle J; Stabley, John N; Gittemeier, Elizabeth M; Opoku-Acheampong, Alexander B; Sieman, Dietmar W; Behnke, Bradley J

2016-07-01

Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes. Copyright © 2016 the American Physiological Society.

Status of iodine in formaldehyde-preserved milk - revisited

International Nuclear Information System (INIS)

Montgomery, D.M.; Gibson, J.E.

1977-01-01

The results of an investigation into the effect of formaldehyde preservation of raw milk in view of the differences observed by Murthy (J. Dairy Sci.; 45:1066 (1962) and J. Dairy Sci.; 49:1190 (1966)) and Thomas (personal communication. (1976)) are reported. The use of the specific electrode method for iodine analysis of formaldehyde-preserved milk has also been investigated. It was found that the Thomas preservation technique for 4 litre milk samples for 131 I analysis was acceptable, and an aliquot of the formaldehyde-preserved milk can be analyzed for total iodide concentration by the electrode method. Milk samples may also be preserved for stable iodide measurement (without iodide carrier addition) by addition of formaldehyde at 0.5 M concentration. (U.K.)

Tumor cell-derived microparticles: a new form of cancer vaccine.

Science.gov (United States)

Zhang, Huafeng; Huang, Bo

2015-08-01

For cancer vaccines, tumor antigen availability is currently not an issue due to technical advances. However, the generation of optimal immune stimulation during vaccination is challenging. We have recently demonstrated that tumor cell-derived microparticles (MP) can function as a new form of potent cancer vaccine by efficiently activating type I interferon pathway in a cGAS/STING dependent manner.

Preliminary results with gadolinium-DTPA in magnetic resonance tomography of bone and soft-tissue tumors

International Nuclear Information System (INIS)

Reiser, M.; Erlemann, R.; Kunze, V.; Bohndorf, K.; Friedmann, G.; Niendorf, H.P.

1987-01-01

MR was performed in 41 patients suffering from benign and malignant bone and soft-tissue tumors before and after intravenous injection of the paramagnetic agent Gadolinium-DTPA (Gd-DTPA). Using T 1 -weighted parameters, the contrast of tumor tissue versus muscle could be increased by Gd-DTPA. Thus, extraosseous extension as well as infiltration of the spinal canal was depicted to better advantage. Inhomogeneities were visualized with higher frequency and improved contrast. In several instances, there was no differentiation between tumor and adjacent edema without application of Gd-DTPA. T 2 -weighted images without Gd-DTPA exhibited higher contrast as compared to T 1 -weighted images after Gd-DTPA. The contrast of tumor tissue versus fat and bone marrow respectively was reduced after applying Gd-DTPA. Thus, for the evaluation of bone marrow infiltration, T 1 -weighted images without Gd-DTPA proved to be indispensable. (orig.) [de

Synthesis and evaluation of two novel 2-nitroimidazole derivatives as potential PET radioligands for tumor imaging

Energy Technology Data Exchange (ETDEWEB)

Zha Zhihao; Zhu Lin [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19014 (United States); Liu Yajing; Du Fenghua; Gan Hongmei; Qiao Jinping [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Kung, Hank F., E-mail: kunghf@gmail.co [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19014 (United States)

2011-05-15

Introduction: Nitroimidazole (azomycin) derivatives labeled with radioisotopes have been developed as cancer imaging and radiotherapeutic agents based on the oncological hypoxic mechanism. By attaching nitroimidazole core with different functional groups, we synthesized new nitroimidazole derivatives and evaluated their potentiality as tumor imaging agents. Methods: Starting with commercially available 2-nitroimidazole, 2-fluoro-N-(2-(2-nitro-1H-imidazol-1-yl)ethyl)acetamide (NEFA, [{sup 19}F]7) and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 2-fluoroacetate (NEFT, [{sup 19}F]8), as well as radiolabeling precursors, the bromo-substituted analogs were quickly synthesized through a three-step synthetic pathway. The precursors were radiolabeled with [{sup 18}F]F{sup -}/18-crown-6/KHCO{sub 3} in dimethyl sulfoxide at 90{sup o}C for 10 min followed by purification with an Oasis HLB cartridge. Biodistribution studies were carried out in EMT-6 tumor-bearing mice. The uptake (%ID/g) in tumors and normal tissues were measured at 30 min postinjection. Liquid chromatography-electrospray ionization mass spectrometry (LC/MS) was used to distinguish metabolites from parent drugs in urine and plasma of rat injected with 'cold' NEFA ([{sup 19}F]7) and NEFT ([{sup 19}F]8). Results: Two radiotracers, [{sup 18}F]NEFA ([{sup 18}F]7) and [{sup 18}F]NEFT ([{sup 18}F]8), were prepared with average yields of 6%-7% and 9%-10% (not decay corrected). Radiochemical purity for both tracers was >95% as determined by HPLC. Biodistribution studies in EMT-6 tumor-bearing mice indicated that the tumor to blood and tumor to liver ratios of both [{sup 18}F]7 (0.96, 0.61) and [{sup 18}F]8 (0.98, 1.10) at 30 min were higher than those observed for [{sup 18}F]FMISO (1) (0.91, 0.59), a well-investigated azomycin-type hypoxia radiotracer. Liquid chromatography-electrospray ionization mass spectrometry analysis demonstrated that fluoroacetate was the main in vivo metabolite for both NEFA ([{sup 19

Altered expression of estrogen receptor-α variant messenger RNAs between adjacent normal breast and breast tumor tissues

International Nuclear Information System (INIS)

Leygue, Etienne; Dotzlaw, Helmut; Watson, Peter H; Murphy, Leigh C

2000-01-01

Using semiquantitative reverse transcription-polymerase chain reaction assays, we investigated the expression of variant messenger RNAs relative to wild-type estrogen receptor (ER)-α messenger RNA in normal breast tissues and their adjacent matched breast tumor tissues. Higher ER variant truncated after sequences encoding exon 2 of the wild-type ER-α (ERC4) messenger RNA and a lower exon 3 deleted ER-α variant (ERD3) messenger RNA relative expression in the tumor compartment were observed in the ER-positive/PR-positive and the ER-positive subsets, respectively. A significantly higher relative expression of exon 5 deleted ER-α varient (ERD5) messenger RNA was observed in tumor components overall. These data demonstrate that changes in the relative expression of ER-α variant messenger RNAs occur between adjacent normal and neoplastic breast tissues. We suggest that these changes might be involved in the mechanisms that underlie breast tumorigenesis. Estrogen receptor (ER)-α and ER-β are believed to mediate the action of estradiol in target tissues. Several ER-α and ER-β variant messenger RNAs have been identified in both normal and neoplastic human tissues. Most of these variants contain a deletion of one or more exons of the wild-type (WT) ER messenger RNAs. The putative proteins that are encoded by these variant messenger RNAs would therefore be missing some functional domains of the WT receptors, and might interfere with WT-ER signaling pathways. The detection of ER-α variants in both normal and neoplastic human breast tissues raised the question of their possible role in breast tumorigenesis. We have previously reported an increased relative expression of exon 5 deleted ER-α variant (ERD5) messenger RNA and of another ER-α variant truncated of all sequences following the exon 2 of the WT ER-α (ERC4) messenger RNA in breast tumor samples versus independent normal breast tissues. In contrast, a decreased relative expression of exon 3 deleted ER

The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors

DEFF Research Database (Denmark)

Seminatore, Christine; Polentes, Jerome; Ellman, Ditte

2010-01-01

Risk of tumorigenesis is a major obstacle to human embryonic and induced pluripotent stem cell therapy. Likely linked to the stage of differentiation of the cells at the time of implantation, formation of teratoma/tumors can also be influenced by factors released by the host tissue. We have...... analyzed the relative effects of the stage of differentiation and the postischemic environment on the formation of adverse structures by transplanted human embryonic stem cell-derived neural progenitors....

Three-dimensional reconstruction of colorectal tumors from serial tissue sections by computer graphics: a preliminary study.

Science.gov (United States)

Kikuchi, S; Matsuzaki, H; Kondo, K; Ohtani, Y; Ihara, A; Hiki, Y; Kakita, A; Kuwao, S

2000-01-01

We present herein the three-dimensional reconstruction of colorectal tumors, with particular reference to growth pattern into each layer of the colorectal wall, and measurement of tumor volume and surface area. Conventional tissue section images of colorectal tumors were analyzed using a computer graphics analysis program. The two-dimensional extent of invasion by each tumor into each layer of intestinal wall were determined from the images of each section. Based on data from multiple sections, tumor and surrounding normal tissue layers were reconstructed three-dimensionally, and volume and surface area of the tumors were determined. Using this technique, three-dimensional morphology of tumor and tumor progression into colorectal wall could be determined. Volume and surface area of the colon tumor were 4871 mm3 and 1741 mm2, respectively. Volume and surface area of the rectal tumor were 1090 mm3 and 877 mm2, respectively. This technique may provide a new approach for pathological analysis of colorectal carcinoma.

Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins.

Science.gov (United States)

Mueller, Jenna L; Harmany, Zachary T; Mito, Jeffrey K; Kennedy, Stephanie A; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G; Willett, Rebecca M; Brown, J Quincy; Ramanujam, Nimmi

2013-01-01

To develop a robust tool for quantitative in situ pathology that allows visualization of heterogeneous tissue morphology and segmentation and quantification of image features. TISSUE EXCISED FROM A GENETICALLY ENGINEERED MOUSE MODEL OF SARCOMA WAS IMAGED USING A SUBCELLULAR RESOLUTION MICROENDOSCOPE AFTER TOPICAL APPLICATION OF A FLUORESCENT ANATOMICAL CONTRAST AGENT: acriflavine. An algorithm based on sparse component analysis (SCA) and the circle transform (CT) was developed for image segmentation and quantification of distinct tissue types. The accuracy of our approach was quantified through simulations of tumor and muscle images. Specifically, tumor, muscle, and tumor+muscle tissue images were simulated because these tissue types were most commonly observed in sarcoma margins. Simulations were based on tissue characteristics observed in pathology slides. The potential clinical utility of our approach was evaluated by imaging excised margins and the tumor bed in a cohort of mice after surgical resection of sarcoma. Simulation experiments revealed that SCA+CT achieved the lowest errors for larger nuclear sizes and for higher contrast ratios (nuclei intensity/background intensity). For imaging of tumor margins, SCA+CT effectively isolated nuclei from tumor, muscle, adipose, and tumor+muscle tissue types. Differences in density were correctly identified with SCA+CT in a cohort of ex vivo and in vivo images, thus illustrating the diagnostic potential of our approach. The combination of a subcellular-resolution microendoscope, acriflavine staining, and SCA+CT can be used to accurately isolate nuclei and quantify their density in anatomical images of heterogeneous tissue.

40 CFR 721.3810 - Formaldehyde, polymers with substituted phenols (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Formaldehyde, polymers with... New Uses for Specific Chemical Substances § 721.3810 Formaldehyde, polymers with substituted phenols... identified generically as Formaldehyde, polymers with substituted phenols (PMN P-99-0558) is subject to...

Formaldehyde as an antiseptic in the production of alcohol from molasses

Energy Technology Data Exchange (ETDEWEB)

Rosa, V J; Stros, F

1962-01-01

The effect of formaldehyde as an antiseptic for the noncontaminated alcohol fermentation of molasses was examined with five different yeasts mash batches containing formaldehyde 0.01%. Following 24 hour cultivation, increase in the activity of formaldehyde-inoculated mash was lowered by 47%; the formaldehyde decreased the alcohol fermentation and lessened the rate of fermentation of sugar by 20% in noncontaminated mash. The decrease in the fermentation rate was also observed during the entire course of fermentation. On the other hand, formaldehyde addition to molasses contaminated with lactic acid bacteria accelerated the fermentation rate.

Giant cell tumor of soft tissues of low malignant potential: A rare diagnosis on fine needle aspiration cytology

Directory of Open Access Journals (Sweden)

Maithili M Kulkarni

2016-01-01

Full Text Available Primary giant cell tumors of soft tissues (GCT-ST are extremely rare soft tissue tumors, located in both superficial and deep soft tissues. They resemble osseous giant cell tumors morphologically and immunohistochemically. The tumor exhibits strong positive immunoreactivity for cluster of differentiation 68 (CD68 within multinucleated osteoclast-like giant cells and focal staining of mononuclear cells. Case reports describing the cytohistological features of this entity are very few. We report a case of GCT-ST of low malignant potential diagnosed on fine needle aspiration (FNA and confirmed on histological and immunohistochemical studies.

Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

Directory of Open Access Journals (Sweden)

Emara Marwan

2010-09-01

Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

DCE-MRI of patient-derived xenograft models of uterine cervix carcinoma: associations with parameters of the tumor microenvironment

Directory of Open Access Journals (Sweden)

Anette Hauge

2017-11-01

Full Text Available Abstract Background Abnormalities in the tumor microenvironment are associated with resistance to treatment, aggressive growth, and poor clinical outcome in patients with advanced cervical cancer. The potential of dynamic contrast-enhanced (DCE MRI to assess the microvascular density (MVD, interstitial fluid pressure (IFP, and hypoxic fraction of patient-derived cervical cancer xenografts was investigated in the present study. Methods Four patient-derived xenograft (PDX models of squamous cell carcinoma of the uterine cervix (BK-12, ED-15, HL-16, and LA-19 were subjected to Gd-DOTA-based DCE-MRI using a 7.05 T preclinical scanner. Parametric images of the volume transfer constant (K trans and the fractional distribution volume (v e of the contrast agent were produced by pharmacokinetic analyses utilizing the standard Tofts model. Whole tumor median values of the DCE-MRI parameters were compared with MVD and the fraction of hypoxic tumor tissue, as determined histologically, and IFP, as measured with a Millar catheter. Results Both on the PDX model level and the single tumor level, a significant inverse correlation was found between K trans and hypoxic fraction. The extent of hypoxia was also associated with the fraction of voxels with unphysiological v e values (v e > 1.0. None of the DCE-MRI parameters were related to MVD or IFP. Conclusions DCE-MRI may provide valuable information on the hypoxic fraction of squamous cell carcinoma of the uterine cervix, and thereby facilitate individualized patient management.

Preparation of carbon dioxide adsorbents from the chemical activation of urea-formaldehyde and melamine-formaldehyde resins

Energy Technology Data Exchange (ETDEWEB)

T.C. Drage; A. Arenillas; K.M. Smith; C. Pevida; S. Piippo; C.E. Snape [University of Nottingham, Nottingham (United Kingdom). Nottingham Fuel and Energy Centre, School of Chemical, Environmental and Mining Engineering

2007-01-15

Adsorption is considered to be one of the more promising technologies for the capture of CO{sub 2} from flue gases. In general, nitrogen enrichment is reported to be effective in enhancing the specific adsorbent-adsorbate interaction for CO{sub 2}. Nitrogen enriched carbons were produced from urea-formaldehyde and melamine-formaldehyde resins polymerised in the presence of K{sub 2}CO{sub 3} as a chemical activation agent, with activation undertaken over a range of temperatures. CO{sub 2} adsorption capacity was determined to be dependent upon both textural properties and more importantly nitrogen functionality. Adsorbents capable of capturing above 8 wt.% CO{sub 2} at 25{sup o}C were produced from the chemical activation of urea-formaldehyde resin at 500{sup o}C. Chemical activation seems to produce more effective adsorbents than CO{sub 2} activation. 29 refs., 4 figs., 3 tabs.

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue

International Nuclear Information System (INIS)

Imanaka, Kazufumi; Tanaka, Koji; Sasai, Keisuke

1984-01-01

We have already reported the effectiveness of active specific immunotherapy based on the immune reaction of low-dose irradiated tumor tissue. In the present study, three kinds of immunotherapeutic methods subdivided by used cells were performed in order to compare each effectiveness. C3H/He mice bearing MM 46 tumor transplanted in the right hind paws received local irradiation with the dose of 3,000 rad on the 6th day, and the above-mentioned three methods, using tumor cells, lymphocytes, and tumor cells combining lymphocytes which were all separated from the topical tumor tissue exposed to 2,000 rad, were applied respectively on the 14 th day. The most effective data were obtained from two groups treated by the immunotherapy with tumor cells combining lymphocytes, which virtually caused the longest survival and best tumor growth control. (author)

Early uptake and continuous accumulation of thallium-201 chloride in a benign mixed tumor of soft tissue: Case Report

Directory of Open Access Journals (Sweden)

Hamada Kenichiro

2010-05-01

Full Text Available Abstract A case of benign mixed tumor of the soft tissue in a 64-year-old Japanese male is presented. He noticed a painless, elastic hard mass sized 3 cm in the right knee, which gradually grew larger and harder in the last 5 years. Magnetic resonance imaging demonstrated a mass lesion embedded in the subcutaneous tissue with low and high signal intensity at T1- and T2-weighted images, respectively. Tl-201 scintigraphy showed an early uptake of Tl-201 within the lesion at 10 minutes after injection, which was slightly decreased but still continued at 2 hours later. The patient underwent a resection of tumor, and the pathological diagnosis was a benign mixed tumor of soft tissue without high vascularity, characterized by histological features similar to pleomorphic adenomas in the salivary glands. Immunohistochemical study proved expression of Na+/K+-ATPase of tumor cells. Overexpression of Na+/K+-ATPase of the tumor might be responsible for the early uptake of Tl-201, and poor vascular structure in this tumor might lead to continuous accumulation. The Tl-201 scintigraphic features of mixed tumor of soft tissue are assessed to resemble those of malignant soft tissue tumors.

Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins.

Directory of Open Access Journals (Sweden)

Jenna L Mueller

Full Text Available To develop a robust tool for quantitative in situ pathology that allows visualization of heterogeneous tissue morphology and segmentation and quantification of image features.TISSUE EXCISED FROM A GENETICALLY ENGINEERED MOUSE MODEL OF SARCOMA WAS IMAGED USING A SUBCELLULAR RESOLUTION MICROENDOSCOPE AFTER TOPICAL APPLICATION OF A FLUORESCENT ANATOMICAL CONTRAST AGENT: acriflavine. An algorithm based on sparse component analysis (SCA and the circle transform (CT was developed for image segmentation and quantification of distinct tissue types. The accuracy of our approach was quantified through simulations of tumor and muscle images. Specifically, tumor, muscle, and tumor+muscle tissue images were simulated because these tissue types were most commonly observed in sarcoma margins. Simulations were based on tissue characteristics observed in pathology slides. The potential clinical utility of our approach was evaluated by imaging excised margins and the tumor bed in a cohort of mice after surgical resection of sarcoma.Simulation experiments revealed that SCA+CT achieved the lowest errors for larger nuclear sizes and for higher contrast ratios (nuclei intensity/background intensity. For imaging of tumor margins, SCA+CT effectively isolated nuclei from tumor, muscle, adipose, and tumor+muscle tissue types. Differences in density were correctly identified with SCA+CT in a cohort of ex vivo and in vivo images, thus illustrating the diagnostic potential of our approach.The combination of a subcellular-resolution microendoscope, acriflavine staining, and SCA+CT can be used to accurately isolate nuclei and quantify their density in anatomical images of heterogeneous tissue.

Formaldehyde: a candidate toxic air contaminant. Final report

Energy Technology Data Exchange (ETDEWEB)

Frye, B.; Parker, T.

1988-03-01

Formaldehyde (HCHO) is a gas widely used in adhesives and resins, textiles, embalming fluids, fungicides, air fresheners, and cosmetics. It is directly emitted into the ambient outdoor air from vehicular and stationary sources, and is also produced in the atmosphere from other substances by photochemical smog processes. The International Agency for Research on Cancer (IARC) has determined that there is sufficient evidence for carcinogenicity of formaldehyde to animals, and limited evidence for carcinogenicity to humans. EPA classifies formaldehyde as a probable human carcinogen with a one in a million risk concentration of 0.08 ppb.

Chemosorption sampling and analysis of formaldehyde in air. Influence on recovery during the simultaneous sampling of formaldehyde, phenol, furfural and furfuryl alcohol

Energy Technology Data Exchange (ETDEWEB)

Andersson, K.; Hallgren, C.; Levin, J.O.; Nilsson, C.A.

1981-12-01

A method based on trapping formaldehyde on a 2,4-dinitrodinitrophenylhydrazine-coated porous polymer (Amberlite XAD-2) was evaluated for air sampling in occupational environments. The aldehyde is converted to its 2,4-dinitrophenylhydrazone on the adsorbent. The influence of some organic compounds which often occur together with formaldehyde-furfural, phenol and furfuryl alcohol--was studied. The results show that the method allows the sampling of formaldehyde in the range 0.01--1.0 mg/m3 of air, based on a 3-1 (15 min) sample and a coating of 1%. Furfural, phenol, and furfuryl alcohol do not interfere and may be conveniently sampled at the same time. Formaldehyde and furfural hydrazones were analyzed by high-performance liquid chromatography, phenol and furfuryl alcohol by gas chromatography.

Metabolic evaluation of skin absorption of tritiated formaldehyde in hairless rats

International Nuclear Information System (INIS)

Trivedi, A.

1993-11-01

Tritiated organics are present as trace impurities in tritium handling facilities. Tritiated formaldehyde has been detected in the atmosphere and gaseous effluents of tritium handling and storage sites. The ability of tritiated formaldehyde to diffuse through the skin is a possible route of intake. Since the metabolism of tritium through this mode of contamination is not currently established, experiments were performed in which tritiated formaldehyde was applied topically on the dorsal skin of hairless rats. These experiments demonstrated that tritium was assimilated and retained in the exposed skin as organically bound tritium (OBT). This retained OBT dominates tritium turnover in the body. OBT retention in the unexposed skin, liver, heart and kidneys was also observed. The loss of tritium from the animals showed that about 10% of the applied tritium was excreted in urine. It is assumed that the rest of the applied activity may have been lost through other excretory pathways, or may not have entered into the body. The biokinetics of tritium excretion is best described by a sum of three exponential functions. Most of the excreted tritium was in the form of OBT (90%) and results in the rapid clearing of OBT in the skin to urine and retention in other tissues. The evaluation of the dose-rate data showed that the dose-rate to exposed skin was almost a magnitude greater than the dose-rate to other organs. (author). 21 refs., 4 tabs., 4 figs

Metabolic evaluation of skin absorption of tritiated formaldehyde in hairless rats

Energy Technology Data Exchange (ETDEWEB)

Trivedi, A

1993-11-01

Tritiated organics are present as trace impurities in tritium handling facilities. Tritiated formaldehyde has been detected in the atmosphere and gaseous effluents of tritium handling and storage sites. The ability of tritiated formaldehyde to diffuse through the skin is a possible route of intake. Since the metabolism of tritium through this mode of contamination is not currently established, experiments were performed in which tritiated formaldehyde was applied topically on the dorsal skin of hairless rats. These experiments demonstrated that tritium was assimilated and retained in the exposed skin as organically bound tritium (OBT). This retained OBT dominates tritium turnover in the body. OBT retention in the unexposed skin, liver, heart and kidneys was also observed. The loss of tritium from the animals showed that about 10% of the applied tritium was excreted in urine. It is assumed that the rest of the applied activity may have been lost through other excretory pathways, or may not have entered into the body. The biokinetics of tritium excretion is best described by a sum of three exponential functions. Most of the excreted tritium was in the form of OBT (90%) and results in the rapid clearing of OBT in the skin to urine and retention in other tissues. The evaluation of the dose-rate data showed that the dose-rate to exposed skin was almost a magnitude greater than the dose-rate to other organs. (author). 21 refs., 4 tabs., 4 figs.

Differential effect of alpha-difluoromethylornithine on the in vivo uptake of 14C-labeled polyamines and methylglyoxal bis(guanylhydrazone) by a rat prostate-derived tumor

International Nuclear Information System (INIS)

Heston, W.D.; Kadmon, D.; Covey, D.F.; Fair, W.R.

1984-01-01

The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both [ 14 C]putrescine and [14 C]spermidine. The in vitro uptake of [ 14 C]putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting [ 14 C]putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of [ 14 C]putrescine and [ 14 C]-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines

Differential effect of alpha-difluoromethylornithine on the in vivo uptake of 14C-labeled polyamines and methylglyoxal bis(guanylhydrazone) by a rat prostate-derived tumor

Energy Technology Data Exchange (ETDEWEB)

Heston, W.D.; Kadmon, D.; Covey, D.F.; Fair, W.R.

1984-03-01

The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both (/sup 14/C)putrescine and (14 C)spermidine. The in vitro uptake of (/sup 14/C)putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting (/sup 14/C)putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of (/sup 14/C)putrescine and (/sup 14/C)-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines.

Formaldehyde cross-linking and structural proteomics: Bridging the gap.

Science.gov (United States)

Srinivasa, Savita; Ding, Xuan; Kast, Juergen

2015-11-01

Proteins are dynamic entities constantly moving and altering their structures based on their functions and interactions inside and outside the cell. Formaldehyde cross-linking combined with mass spectrometry can accurately capture interactions of these rapidly changing biomolecules while maintaining their physiological surroundings. Even with its numerous established uses in biology and compatibility with mass spectrometry, formaldehyde has not yet been applied in structural proteomics. However, formaldehyde cross-linking is moving toward analyzing tertiary structure, which conventional cross-linkers have already accomplished. The purpose of this review is to describe the potential of formaldehyde cross-linking in structural proteomics by highlighting its applications, characteristics and current status in the field. Copyright © 2015 Elsevier Inc. All rights reserved.

Tumor suppressor roles of CENP-E and Nsl1 in Drosophila epithelial tissues.

Science.gov (United States)

Clemente-Ruiz, Marta; Muzzopappa, Mariana; Milán, Marco

2014-01-01

Depletion of spindle assembly checkpoint (SAC) genes in Drosophila epithelial tissues leads to JNK-dependent programmed cell death and additional blockade of the apoptotic program drives tumorigenesis. A recent report proposes that chromosomal instability (CIN) is not the driving force in the tumorigenic response of the SAC-deficient tissue, and that checkpoint proteins exert a SAC-independent tumor suppressor role. This notion is based on observations that the depletion of CENP-E levels or prevention of Bub3 from binding to the kinetochore in Drosophila tissues unable to activate the apoptotic program induces CIN but does not cause hyperproliferation. Here we re-examined this proposal. In contrast to the previous report, we observed that depletion of CENP-E or Nsl1-the latter mediating kinetochore targeting of Bub3-in epithelial tissues unable to activate the apoptotic program induces significant levels of aneuploidy and drives tumor-like growth. The induction of the JNK transcriptional targets Wingless, a mitogenic molecule, and MMP1, a matrix metaloproteinase 1 involved in basement membrane degradation was also observed in these tumors. An identical response of the tissue was previously detected upon depletion of several SAC genes or genes involved in spindle assembly, chromatin condensation, and cytokinesis, all of which have been described to cause CIN. All together, these results reinforce the role of CIN in driving tumorigenesis in Drosophila epithelial tissues and question the proposed SAC-independent roles of checkpoint proteins in suppressing tumorigenesis. Differences in aneuploidy rates might explain the discrepancy between the previous report and our results.

21 CFR 177.1900 - Urea-formaldehyde resins in molded articles.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Urea-formaldehyde resins in molded articles. 177... for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1900 Urea-formaldehyde resins in molded articles. Urea-formaldehyde resins may be safely used as the food-contact surface...

Preliminary study: Formaldehyde exposure in laboratories of Sharjah university in UAE

OpenAIRE

Ahmed, Hafiz Omer

2011-01-01

Objectives : Laboratory technicians, students, and instructors are at high risk, because they deal with chemicals including formaldehyde. Thus, this preliminary study was conducted to measure the concentration of formaldehyde in the laboratories of the University of Sharjah in UAE. Materials and Methods: Thirty-two air samples were collected and analyzed for formaldehyde using National Institute for Occupational Safety and Health (NIOSH) method 3500. In this method, formaldehyde reacts with c...

Canine tumor and normal tissue response to heat and radiation

International Nuclear Information System (INIS)

Gillette, E.L.; McChesney, S.L.

1985-01-01

Oral squamous cell carcinomas of dogs were treated with either irradiation alone or combined with hyperthermia. Tumor control was assessed as no evidence of disease one year following treatment. Dogs were randomized to variable radiation doses which were given in ten fractions three times a week for three weeks. Heat was given three hours after the first and third radiation dose each week for seven treatments. The attempt was made to achieve a minimum tumor temperature of 42 0 C for thirty minutes with a maximum normal tissue temperature of 40 0 C. It was usually possible to selectively heat tumors. The TCD 50 for irradiation alone was about 400 rads greater than for heat plus irradiation. The dose response curve for heat plus radiation was much steeper than for radiation alone indicating less heterogeneity of tumor response. That also implies a much greater effectiveness of radiation combined with heat at higher tumor control probabilities. Early necrosis caused by heating healed with conservative management. No increase in late radiation necrosis was observed

Value of the Strain Ratio on Ultrasonic Elastography for Differentiation of Benign and Malignant Soft Tissue Tumors.

Science.gov (United States)

Hahn, Seok; Lee, Young Han; Lee, Seung Hyun; Suh, Jin-Suck

2017-01-01

The purpose of this study was to evaluate whether the strain ratio provides additional value to conventional visual elasticity scores in the differentiation of benign and malignant soft tissue tumors by ultrasonic elastography. The Institutional Review Board approved the protocol of this retrospective review. Seventy-three patients who underwent elastography and had a soft tissue mass pathologically confirmed by ultrasound-guided core biopsy or surgical excision were enrolled from April 2012 through October 2014. On elastography, elasticity scores were determined with a 5-point visual scale, and the strain ratio to adjacent soft tissue at the same depth was calculated. Tumors were divided into benign and malignant groups according to the pathologic diagnoses. Elasticity scores and strain ratios were compared between benign and malignant groups, and diagnostic performance was evaluated by receiver operating characteristic curves. Of the 73 patients, 40 had benign tumors, and 33 had malignant tumors. Strain ratios (P = .003) and elasticity scores (P = .048) were significantly different between pathologic results. The areas under the receiver operating characteristic curves were 0.700 (95% confidence interval, 0.581-0.802) for the strain ratio and 0.623 (95% confidence interval, 0.515-0.746) for elastography. The strain ratios of malignant soft tissue tumors were lower than those of benign tumors and showed better diagnostic performance than did elasticity scores. The strain ratio can be used as a diagnostic indicator to predict the malignant potential of soft tissue tumors. © 2016 by the American Institute of Ultrasound in Medicine.

A comparative study between magnetic resonance imaging and histological findings of bone and soft tissue tumors

International Nuclear Information System (INIS)

Itoh, Koichi

1995-01-01

Diagnostic methodology for bone and soft tissue tumors has made great strides recently through the development of magnetic resonance imaging (MRI). Here we report a comparative assessment of the histological findings of bone and soft tissue tumors with MRI from 212 cases. The accuracy of a qualitative diagnosis was observed in a solitary bone cyst, enchondroma, giant cell tumor, chondrosarcoma, lipoma, hemangioma, neurinoma, and in a synovial cyst. However, the qualitative diagnosis of a malignant tumor was difficult because of the variety of the intratumoral histological changes. An enhanced-image using Gd-DTPA was useful for differentiation of the viable region in the internal area of a tumor, discrimination of the reactive zone of an edema or assessing vascularity, and for discrimination between a cyst and a solid tumor. Based on comparison with findings from the excised specimen, it was found that histological changes such as calcification, fibrosis, hemorrhaging and necrosis, and the presence or absence of a tumor capsule had been reflected accurately on MR images. However, infiltration of the tumor into the bone cortex and into the articular cartilage were found frequently to be false-positive on MRI. Although problems remained to be solved regarding the evaluation of the presence or absence of tumor infiltration into adjacent tissue, the depiction of periosteal reaction, and regarding differentiation from inflammatory disease, MRI was a very useful information source for operative planning because it could evaluate the relationship between the tumor and adjacent blood vessels or nerves, the effect of preoperative therapy, and effectively discriminate between benign and malignant tumors. (author)

A Hybrid DE-RGSO-ELM for Brain Tumor Tissue Categorization in 3D Magnetic Resonance Images

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K. Kothavari

2014-01-01

Full Text Available Medical diagnostics, a technique used for visualizing the internal structures and functions of human body, serves as a scientific tool to assist physicians and involves direct use of digital imaging system analysis. In this scenario, identification of brain tumors is complex in the diagnostic process. Magnetic resonance imaging (MRI technique is noted to best assist tissue contrast for anatomical details and also carries out mechanisms for investigating the brain by functional imaging in tumor predictions. Considering 3D MRI model, analyzing the anatomy features and tissue characteristics of brain tumor is complex in nature. Henceforth, in this work, feature extraction is carried out by computing 3D gray-level cooccurence matrix (3D GLCM and run-length matrix (RLM and feature subselection for dimensionality reduction is performed with basic differential evolution (DE algorithm. Classification is performed using proposed extreme learning machine (ELM, with refined group search optimizer (RGSO technique, to select the best parameters for better simplification and training of the classifier for brain tissue and tumor characterization as white matter (WM, gray matter (GM, cerebrospinal fluid (CSF, and tumor. Extreme learning machine outperforms the standard binary linear SVM and BPN for medical image classifier and proves better in classifying healthy and tumor tissues. The comparison between the algorithms proves that the mean and standard deviation produced by volumetric feature extraction analysis are higher than the other approaches. The proposed work is designed for pathological brain tumor classification and for 3D MRI tumor image segmentation. The proposed approaches are applied for real time datasets and benchmark datasets taken from dataset repositories.

Hypoxia and hydrogen sulfide differentially affect normal and tumor-derived vascular endothelium

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Serena Bianco

2017-08-01

Full Text Available Background: endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (H2S, NO and CO. Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, H2S can be both cytoprotective and detrimental depending on its concentration. H2S effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis. We previously demonstrated that H2S is proangiogenic for tumoral but not for normal endothelium and this may represent a target for antiangiogenic therapeutical strategies. Methods: in this work, we investigate cell viability, migration and tubulogenesis on human EC derived from two different tumors, breast and renal carcinoma (BTEC and RTEC, compared to normal microvascular endothelium (HMEC under oxidative stress, hypoxia and treatment with exogenous H2S. Results: all EC types are similarly sensitive to oxidative stress induced by hydrogen peroxide; chemical hypoxia differentially affects endothelial viability, that results unaltered by real hypoxia. H2S neither affects cell viability nor prevents hypoxia and H2O2-induced damage. Endothelial migration is enhanced by hypoxia, while tubulogenesis is inhibited for all EC types. H2S acts differentially on EC migration and tubulogenesis. Conclusions: these data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions. Keywords: Hydrogen sulfide, Human microvascular endothelial cells, Human breast carcinoma-derived EC, Human renal carcinoma-derived EC, Tumor angiogenesis

Gastric cancer tissue-derived mesenchymal stem cells impact peripheral blood mononuclear cells via disruption of Treg/Th17 balance to promote gastric cancer progression.

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Wang, Mei; Chen, Bin; Sun, Xiao-Xian; Zhao, Xiang-Dong; Zhao, Yuan-Yuan; Sun, Li; Xu, Chang-Gen; Shen, Bo; Su, Zhao-Liang; Xu, Wen-Rong; Zhu, Wei

2017-12-01

Gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) are important resident stromal cells in the tumor microenvironment (TME) and have been shown to play a key role in gastric cancer progression. Whether GC-MSCs exert a tumor-promoting function by affecting anti-tumor immunity is still unclear. In this study, we used GC-MSC conditioned medium (GC-MSC-CM) to pretreat peripheral blood mononuclear cells (PBMCs) from healthy donors. We found that GC-MSC-CM pretreatment markedly reversed the inhibitory effect of PBMCs on gastric cancer growth in vivo, but did not affect functions of PBMCs on gastric cancer cell proliferation, cell cycle and apoptosis in vitro. PBMCs pretreated with GC-MSC-CM significantly promoted gastric cancer migration and epithelial-mesenchymal transition in vitro and liver metastases in vivo. Flow cytometry analysis showed that GC-MSC-CM pretreatment increased the proportion of Treg cells and reduced that of Th17 cells in PBMCs. CFSE labeling and naïve CD4 + T cells differentiation analysis revealed that GC-MSC-CM disrupted the Treg/Th17 balance in PBMCs by suppressing Th17 cell proliferation and inducing differentiation of Treg cells. Overall, our collective results indicate that GC-MSCs impair the anti-tumor immune response of PBMCs through disruption of Treg/Th17 balance, thus providing new evidence that gastric cancer tissue-derived MSCs contribute to the immunosuppressive TME. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of ESR1 Mutations in Tumor Tissue and Matched Plasma Samples from Metastatic Breast Cancer Patients

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Takashi Takeshita

2017-10-01

Full Text Available BACKGROUND: ESR1 mutation in circulating cell-free DNA (cfDNA is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue. METHODS: ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC (35 tumor tissue samples and 67 plasma samples. RESULTS: Of the 35 paired samples, 26 (74.3% were concordant: one patient had detectable ESR1 mutations both plasma (ESR1 Y537S/Y537N and tumor tissue (ESR1 Y537S/Y537C, and 25 had WT ESR1 alleles in both. Nine (25.7% had discordance between the plasma and tissue results: five had mutations detected only in their tumor tissue (two Y537S, one Y537C, one D538G, and one Y537S/Y537N/D538G, and four had mutations detected only in their plasma (one Y537S, one Y537N, and two Y537S/Y537N/D538G. Furthermore, longitudinal plasma samples from 19 patients were used to assess changes in the presence of ESR1 mutations during treatment. Eleven patients had cfDNA ESR1 mutations over the course of treatment. A total of eight of 11 patients with MBC with cfDNA ESR1 mutations (72.7% had the polyclonal mutations. CONCLUSION: We have shown the independent distribution of ESR1 mutations between plasma and tumor tissue in 35 patients with MBC.

Expression of preoperative KISS1 gene in tumor tissue with epithelial ovarian cancer and its prognostic value.

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Cao, Fang; Chen, Liping; Liu, Manhua; Lin, Weiwei; Ji, Jinlong; You, Jun; Qiao, Fenghai; Liu, Hongbin

2016-11-01

Our study aimed to elucidate the role of Kisspeptin (KISS1) in tumor tissues of patients with epithelial ovarian cancer (EOC) and investigate the prognostic value of this biomarker.Forty EOC patients and 20 uterine fibroids female patients with healthy ovaries undergoing cytoreductive surgery between January 2010 and January 2014 in our hospital were enrolled in this study. KISS1 expression in tumor and normal tissues was detected. Correlations between clinic-pathologic variables and KISS1 expression in EOC tissues and the prognostic value of KISS1 for overall survival were evaluated.During the follow-up of 11.2 to 62.1 months, the overall survival rate and mean survival time were 28.9% (11/38) and 38.35 ± 2.84 months. Preoperative KISS1 mRNA was higher in tumor tissue than in normal tissue (P <0.001), and it was associated with histologic grade of tumor, surgical FIGO stage, metastasis, and residual tumor size (all P <0.05). Multivariate survival analysis indicated significant influence of residual tumor size (HR = 2.357, P = 0.039) and preoperative KISS1 mRNA (HR = 0.0001, P <0.001) on mean survival time. Patients with low KISS1 mRNA expression had shorter survival time than those with high expression (P = 0.001).Preoperative KISS1 mRNA was a potential prognostic biomarker for EOC, and high preoperative KISS1 expression indicated a favorable prognosis.

Diagnostic, evaluation and handling of the tumors of soft tissues. Experience in the Central Military Hospital

International Nuclear Information System (INIS)

Pineda Acero, Gustavo Adolfo; Torres Quintero, Pio

2001-01-01

With the purpose of analyzing the experience of the orthopedics service and traumatology of the central military hospital in the treatment of the tumors of soft tissues, it carries out a descriptive observational study, type series of cases and retrospective. The incidence of the tumors of soft tissues compared with carcinomas and other neoplasia, constitutes less than 1% of all cancerous and the benign ones are more common than the wicked ones in a range of 100:1. The knowledge of the classification, stadification, evaluation strategies, previous biopsy, surgical treatment, radiotherapy y/o chemotherapy is vital for a good final result. 29 clinical histories were included of patient with tumoral lesions in the soft tissues, valued in the central military hospital between March of 1996 and March of 2001. The age average was of 39 years and the pursuit of 24 months. In most of the cases the anatomical commitment belonged to the inferior members (93%), 79% for benign tumors and 21% for wicked tumors. To avoid incorrect diagnoses and inappropriate treatments it is necessary the coordinated evaluation of all multidisciplinary team

Prebiotic Synthesis of Autocatalytic Products From Formaldehyde-Derived Sugars as the Carbon and Energy Source

Science.gov (United States)

Weber, Arthur L.

2003-01-01

Our research objective is to understand and model the chemical processes on the primitive Earth that generated the first autocatalytic molecules and microstructures involved in the origin of life. Our approach involves: (a) investigation of a model origin-of-life process named the Sugar Model that is based on the reaction of formaldehyde- derived sugars (trioses and tetroses) with ammonia, and (b) elucidation of the constraints imposed on the chemistry of the origin of life by the fixed energies and rates of C,H,O-organic reactions under mild aqueous conditions. Recently, we demonstrated that under mild aqueous conditions the Sugar Model process yields autocatalytic products, and generates organic micropherules (2-20 micron dia.) that exhibit budding, size uniformity, and chain formation. We also discovered that the sugar substrates of the Sugar Model are capable of reducing nitrite to ammonia under mild aqueous conditions. In addition studies done in collaboration with Sandra Pizzarrello (Arizona State University) revealed that chiral amino acids (including meteoritic isovaline) catalyze both the synthesis and specific handedness of chiral sugars. Our systematic survey of the energies and rates of reactions of C,H,O-organic substrates under mild aqueous conditions revealed several general principles (rules) that govern the direction and rate of organic reactions. These reactivity principles constrain the structure of chemical pathways used in the origin of life, and in modern and primitive metabolism.

Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

DEFF Research Database (Denmark)

Schrama, D.; Voigt, H.; Eggert, A.O.

2008-01-01

BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...... response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction...... of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells...

Influence of precision of emission characteristic parameters on model prediction error of VOCs/formaldehyde from dry building material.

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Wenjuan Wei

Full Text Available Mass transfer models are useful in predicting the emissions of volatile organic compounds (VOCs and formaldehyde from building materials in indoor environments. They are also useful for human exposure evaluation and in sustainable building design. The measurement errors in the emission characteristic parameters in these mass transfer models, i.e., the initial emittable concentration (C 0, the diffusion coefficient (D, and the partition coefficient (K, can result in errors in predicting indoor VOC and formaldehyde concentrations. These errors have not yet been quantitatively well analyzed in the literature. This paper addresses this by using modelling to assess these errors for some typical building conditions. The error in C 0, as measured in environmental chambers and applied to a reference living room in Beijing, has the largest influence on the model prediction error in indoor VOC and formaldehyde concentration, while the error in K has the least effect. A correlation between the errors in D, K, and C 0 and the error in the indoor VOC and formaldehyde concentration prediction is then derived for engineering applications. In addition, the influence of temperature on the model prediction of emissions is investigated. It shows the impact of temperature fluctuations on the prediction errors in indoor VOC and formaldehyde concentrations to be less than 7% at 23±0.5°C and less than 30% at 23±2°C.

Isolation and expansion of adipose-derived stem cells for tissue engineering

DEFF Research Database (Denmark)

Fink, Trine; Rasmussen, Jeppe Grøndahl; Lund, Pia

2011-01-01

For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs for subseq......For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs...

Radiation-chemical hardening of phenol-formaldehyde oligomers

International Nuclear Information System (INIS)

Shlapatskaya, V.V.; Omel'chenko, S.I.

1978-01-01

Radiation-chemical hardening of phenol formaldehyde oligomers of the resol type has been studied in the presence of furfural and diallylphthalate diluents. The samples have been hardened on an electron accelerator at an electron energy of 1.0-1.1 MeV and a dose rate of 2-3 Mrad/s. The kinetics of hardening has been studied on the yield of gel fraction within the range of absorbed doses from 7 to 400 Mrad. Radiation-chemical hardening of the studied compositions is activated with sensitizers, namely, amines, metal chlorides, and heterocyclic derivatives of metals. Furfural and diallylphthalate compositions are suitable for forming glass-fibre plastic items by the wet method and coatings under the action of ionizing radiations

Accelerated growth of B16BL6 tumor in mice through efficient uptake of their own exosomes by B16BL6 cells

OpenAIRE

Matsumoto, Akihiro; Takahashi, Yuki; Nishikawa, Makiya; Sano, Kohei; Morishita, Masaki; Charoenviriyakul, Chonlada; Saji, Hideo; Takakura, Yoshinobu

2017-01-01

Exosomes are extracellular vesicles released by various cell types and play roles in cell?cell communication. Several studies indicate that cancer cell?derived exosomes play important pathophysiological roles in tumor progression. Biodistribution of cancer cell?derived exosomes in tumor tissue is an important factor for determining their role in tumor proliferation; however, limited studies have assessed the biodistribution of exosomes in tumor tissues. In the present study, we examined the e...

Preliminary experience using dynamic MRI at 3.0 Tesla for evaluation of soft tissue tumors.

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Park, Michael Yong; Jee, Won-Hee; Kim, Sun Ki; Lee, So-Yeon; Jung, Joon-Yong

2013-01-01

We aimed to evaluate the use of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) at 3.0 T for differentiating the benign from malignant soft tissue tumors. Also we aimed to assess whether the shorter length of DCE-MRI protocols are adequate, and to evaluate the effect of temporal resolution. Dynamic contrast-enhanced magnetic resonance imaging, at 3.0 T with a 1 second temporal resolution in 13 patients with pathologically confirmed soft tissue tumors, was analyzed. Visual assessment of time-signal curves, subtraction images, maximal relative enhancement at the first (maximal peak enhancement [Emax]/1) and second (Emax/2) minutes, Emax, steepest slope calculated by using various time intervals (5, 30, 60 seconds), and the start of dynamic enhancement were analyzed. The 13 tumors were comprised of seven benign and six malignant soft tissue neoplasms. Washout on time-signal curves was seen on three (50%) malignant tumors and one (14%) benign one. The most discriminating DCE-MRI parameter was the steepest slope calculated, by using at 5-second intervals, followed by Emax/1 and Emax/2. All of the steepest slope values occurred within 2 minutes of the dynamic study. Start of dynamic enhancement did not show a significant difference, but no malignant tumor rendered a value greater than 14 seconds. The steepest slope and early relative enhancement have the potential for differentiating benign from malignant soft tissue tumors. Short-length rather than long-length DCE-MRI protocol may be adequate for our purpose. The steepest slope parameters require a short temporal resolution, while maximal peak enhancement parameter may be more optimal for a longer temporal resolution.

Influence of indoor formaldehyde pollution on respiratory system ...

African Journals Online (AJOL)

Background The decoration of interior spaces can lead to dangerous levels of indoor formaldehyde pollution. Exposure to indoor air pollution may be responsible for nearly 2 million deaths per year in developing countries. Objectives To assess the prevalence of indoor formaldehyde pollution caused by decoration and ...

Electrodeposition of gold from formaldehyde-sulfite baths: bath stability and deposits characterization

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Juliana L. Cardoso

2011-01-01

Full Text Available It was investigated Au(I-sulfite baths containing formaldehyde. As a result, high stability was achieved for baths containing formaldehyde concentration close to 10 mL L-1 with a lifetime superior to 600 days. On the other hand, cyclic voltammograms indicated that the increase of formaldehyde concentration in the bath promotes decreasing of the maximum cathodic current, so that, if the formaldehyde concentration is high, the surface areal concentration of gold will be low. Also, the lowest surface roughness was obtained for 10 mL L-1 of formaldehyde.

Optically measured microvascular blood flow contrast of malignant breast tumors.

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Regine Choe

Full Text Available Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS, a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63; tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66, and using normal tissue in the contralateral breast was 2.27 (1.90-2.70. Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography.

Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution

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Ashley M. Laughney

2015-08-01

Full Text Available Numerical chromosomal instability is a ubiquitous feature of human neoplasms. Due to experimental limitations, fundamental characteristics of karyotypic changes in cancer are poorly understood. Using an experimentally inspired stochastic model, based on the potency and chromosomal distribution of oncogenes and tumor suppressor genes, we show that cancer cells have evolved to exist within a narrow range of chromosome missegregation rates that optimizes phenotypic heterogeneity and clonal survival. Departure from this range reduces clonal fitness and limits subclonal diversity. Mapping of the aneuploid fitness landscape reveals a highly favorable, commonly observed, near-triploid state onto which evolving diploid- and tetraploid-derived populations spontaneously converge, albeit at a much lower fitness cost for the latter. Finally, by analyzing 1,368 chromosomal translocation events in five human cancers, we find that karyotypic evolution also shapes chromosomal translocation patterns by selecting for more oncogenic derivative chromosomes. Thus, chromosomal instability can generate the heterogeneity required for Darwinian tumor evolution.

Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism.

Science.gov (United States)

Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

2016-02-27

Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions.

Tissue-Derived Extracellular Matrix Bioscaffolds: Emerging Applications in Cartilage and Meniscus Repair.

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Monibi, Farrah A; Cook, James L

2017-08-01

Musculoskeletal injuries are a common problem in orthopedic practice. Given the long-term consequences of unaddressed cartilage and meniscal pathology, a number of treatments have been attempted to stimulate repair or to replace the injured tissue. Despite advances in orthopedic surgery, effective treatments for cartilage and meniscus injuries remain a significant clinical challenge. Tissue engineering is a developing field that aims to regenerate injured tissues with a combination of cells, scaffolds, and signals. Many natural and synthetic scaffold materials have been developed and tested for the repair and restoration of a number of musculoskeletal tissues. Among these, biological scaffolds derived from cell and tissue-derived extracellular matrix (ECM) have shown great promise in tissue engineering given the critical role of the ECM for maintaining the biological and biomechanical properties, structure, and function of native tissues. This review article presents emerging applications for tissue-derived ECM scaffolds in cartilage and meniscus repair. We examine normal ECM composition and the current and future methods for potential treatment of articular cartilage and meniscal defects with decellularized scaffolds.

YKL-40 protein in osteosarcoma tumor tissue

DEFF Research Database (Denmark)

Thorn, Andrea Pohly; Daugaard, Søren; Christensen, Lise Hanne

2016-01-01

YKL-40, a cellular glycoprotein isolated from the human osteosarcoma (OS) cell line MG63, is increased in the blood of patients with various types of cancer, and is found as an independent prognostic variable for survival. YKL-40 is also present with variable intensity in the tumor cells of some...... cancer types, but survival results have been conflicting. The aim of this study was to investigate the tissue expression of YKL-40 and its possible role as a predictive marker in patients with OS. Forty-eight patients were included in the study. Diagnostic biopsies were analyzed by immunohistochemistry...

TRANSCRIPTOMIC ANALYSIS OF F344 RAT NASAL EPITHELIUM SUGGESTS THAT THE LACK OF CARCINOGENIC RESPONSE TO GLUTARALDEHYDE IS DUE TO ITS GREATER TOXICITY COMPARED TO FORMALDEHYDE

Science.gov (United States)

Formaldehyde is cytotoxic and carcinogenic to the rat nasal respiratory epithelium inducing tumors after 12 months. Glutaraldehyde is also cytotoxic but is not carcinogenic to nasal epithelium even after 24 months. Both aldehydes induce similar acute and subchronic histopathology...

Release rate of diazinon from microcapsule based on melamine formaldehyde

Science.gov (United States)

Noviana Utami C., S.; Rochmadi

2018-04-01

The microcapsule containing diazinon as the core material and melamine formaldehyde as the membrane material have been synthesized by in situ polymerization method. The microcapsule membrane in this research is melamine formaldehyde (MF). This research aims to study the effect of pH and temperature on the release rate of diazinon from microcapsule based on melamine formaldehyde in aqueous medium. The results showed that pH and temperature has little effect on the release rate of diazinon from microcapsule based on melamine formaldehyde. This is due to the diffusion through the microcapsule membrane is not influenced by the pH and temperature of the solution outside of microcapsule.

Utility of Normal Tissue-to-Tumor {alpha}/{beta} Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

Energy Technology Data Exchange (ETDEWEB)

Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Jin Jianyue [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Chang, Albert J. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

2013-01-01

Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue {alpha}/{beta} ratio divided by the tumor {alpha}/{beta} times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified.

Anti-angiogenesis therapy based on the bone marrow-derived stromal cells genetically engineered to express sFlt-1 in mouse tumor model

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Chen X-C

2008-10-01

Full Text Available Abstract Background Bone marrow-derived stromal cells (BMSCs are important for development, tissue cell replenishment, and wound healing in physiological and pathological conditions. BMSCs were found to preferably reach sites undergoing the process of cell proliferation, such as wound and tumor, suggesting that BMSCs may be used as a vehicle for gene therapy of tumor. Methods Mouse BMSCs were loaded with recombinant adenoviruses which express soluble Vascular Endothelial Growth Factor Receptor-1 (sFlt-1. The anti-angiogenesis of sFlt-1 in BMSCs was determined using endothelial cells proliferation inhibition assay and alginate encapsulation assay. The anti-tumor effects of BMSCs expressing sFlt-1 through tail-vein infusion were evaluated in two mouse tumor metastases models. Results BMSCs genetically modified with Adv-GFP-sFlt-1 could effectively express and secret sFlt-1. BMSCs loaded with sFlt-1 gene could preferentially home to tumor loci and decrease lung metastases and prolong lifespan in mouse tumor model through inducing anti-angiogenesis and apoptosis in tumors. Conclusion We demonstrated that BMSCs might be employed as a promising vehicle for tumor gene therapy which can effectively not only improve the concentration of anticancer therapeutics in tumors, but also modify the tumor microenvironment.

Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

International Nuclear Information System (INIS)

Ikuta, Togo; Kurosumi, Masafumi; Yatsuoka, Toshimasa; Nishimura, Yoji

2016-01-01

Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc"M"i"n"/"+mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

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Ikuta, Togo, E-mail: togo@cancer-c.pref.saitama.jp [Department of Cancer Prevention, Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Kurosumi, Masafumi, E-mail: mkurosumi@cancer-c.pref.saitama.jp [Division of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Yatsuoka, Toshimasa, E-mail: yatsuoka-gi@umin.ac.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Nishimura, Yoji, E-mail: yojinish@cancr-c.pref.saitama.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan)

2016-05-01

Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc{sup Min/+}mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors

International Nuclear Information System (INIS)

Niimi, Rui; Matsumine, Akihiko; Iino, Takahiro; Nakazora, Shigeto; Nakamura, Tomoki; Uchida, Atsumasa; Sudo, Akihiro

2013-01-01

Neural-cadherin (N-cadherin) is one of the most important molecules involved in tissue morphogenesis, wound healing, and the maintenance of tissue integrity. Recently, the cleavage of N-cadherin has become a focus of attention in the field of cancer biology. Cadherin and their ectodomain proteolytic shedding play important roles during cancer progression. The aims of this study are to investigate the serum soluble N-cadherin (sN-CAD) levels in patients with malignant bone and soft tissue tumors, and to evaluate the prognostic significance of the sN-CAD levels. We examined the level of serum sN-CAD using an ELISA in 80 malignant bone and soft tissue tumors (bone sarcoma, n = 23; soft tissue sarcoma, n = 50; metastatic cancer, n = 7) and 87 normal controls. The mean age of the patients was 51 years (range, 10–85 years) and the mean follow-up period was 43 months (range, 1–115 months). The median serum sN-CAD level was 1,267 ng/ml (range, 135–2,860 ng/ml) in all patients. The mean serum sN-CAD level was 1,269 ng/ml (range, 360–2,860 ng/ml) in sarcoma patients, otherwise 1,246 ng/ml (range, 135–2,140 ng/ml) in cancer patients. The sN-CAD levels in patient were higher than those found in the controls, who had a median serum level of 108 ng/ml (range, 0–540 ng/ml). The patients with tumors larger than 5 cm had higher serum sN-CAD levels than the patients with tumors smaller than 5 cm. The histological grade in the patients with higher serum sN-CAD levels was higher than that in the patients with lower serum sN-CAD levels. A univariate analysis demonstrated that the patients with higher serum sN-CAD levels showed a worse disease-free survival rate, local recurrence-free survival rate, metastasis-free survival rate, and overall survival rate compared to those with lower serum sN-CAD levels. In the multivariate analysis, sN-CAD was an independent factor predicting disease-free survival. sN-CAD is a biomarker for malignant bone and soft tissue tumors, and a

Role of Tumor-Derived Chemokines in Osteolytic Bone Metastasis

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Salvatore J. Coniglio

2018-06-01

Full Text Available Metastasis is the primary cause of mortality and morbidity in cancer patients. The bone marrow is a common destination for many malignant cancers, including breast carcinoma (BC, prostate carcinoma, multiple myeloma, lung carcinoma, uterine cancer, thyroid cancer, bladder cancer, and neuroblastoma. The molecular mechanism by which metastatic cancer are able to recognize, infiltrate, and colonize bone are still unclear. Chemokines are small soluble proteins which under normal physiological conditions mediate chemotactic trafficking of leukocytes to specific tissues in the body. In the context of metastasis, the best characterized role for the chemokine system is in the regulation of primary tumor growth, survival, invasion, and homing to specific secondary sites. However, there is ample evidence that metastatic tumors exploit chemokines to modulate the metastatic niche within bone which ultimately results in osteolytic bone disease. In this review, we examine the role of chemokines in metastatic tumor growth within bone. In particular, the chemokines CCL2, CCL3, IL-8/CXCL8, and CXCL12 are consistently involved in promoting osteoclastogenesis and tumor growth. We will also evaluate the suitability of chemokines as targets for chemotherapy with the use of neutralizing antibodies and chemokine receptor-specific antagonists.

CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis.

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Dondossola, Eleonora; Rangel, Roberto; Guzman-Rojas, Liliana; Barbu, Elena M; Hosoya, Hitomi; St John, Lisa S; Molldrem, Jeffrey J; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2013-12-17

Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+) myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs.

Advances of mesenchymal stem cells derived from bone marrow and dental tissue in craniofacial tissue engineering.

Science.gov (United States)

Yang, Maobin; Zhang, Hongming; Gangolli, Riddhi

2014-05-01

Bone and dental tissues in craniofacial region work as an important aesthetic and functional unit. Reconstruction of craniofacial tissue defects is highly expected to ensure patients to maintain good quality of life. Tissue engineering and regenerative medicine have been developed in the last two decades, and been advanced with the stem cell technology. Bone marrow derived mesenchymal stem cells are one of the most extensively studied post-natal stem cell population, and are widely utilized in cell-based therapy. Dental tissue derived mesenchymal stem cells are a relatively new stem cell population that isolated from various dental tissues. These cells can undergo multilineage differentiation including osteogenic and odontogenic differentiation, thus provide an alternative source of mesenchymal stem cells for tissue engineering. In this review, we discuss the important issues in mesenchymal stem cell biology including the origin and functions of mesenchymal stem cells, compare the properties of these two types of mesenchymal cells, update recent basic research and clinic applications in this field, and address important future challenges.

Local Control of Lung Derived Tumors by Diffusing Alpha-Emitting Atoms Released From Intratumoral Wires Loaded With Radium-224

International Nuclear Information System (INIS)

Cooks, Tomer; Schmidt, Michael; Bittan, Hadas; Lazarov, Elinor; Arazi, Lior; Kelson, Itzhak; Keisari, Yona

2009-01-01

Purpose: Diffusing alpha-emitters radiation therapy (DART) is a new form of brachytherapy enabling the treatment of solid tumors with alpha radiation. The present study examines the antitumoral effects resulting from the release of alpha emitting radioisotopes into solid lung carcinoma (LL2, A427, and NCI-H520). Methods and Materials: An in vitro setup tested the dose-dependent killing of tumor cells exposed to alpha particles. In in vivo studies, radioactive wires (0.3 mm diameter, 5 mm long) with 224 Ra activities in the range of 21-38 kBq were inserted into LL/2 tumors in C57BL/6 mice and into human-derived A427 or NCI-H520 tumors in athymic mice. The efficacy of the short-lived daughters of 224 Ra to produce tumor growth retardation and prolong life was assessed, and the spread of radioisotopes inside tumors was measured using autoradiography. Results: The insertion of a single DART wire into the center of 6- to 7-mm tumors had a pronounced retardation effect on tumor growth, leading to a significant inhibition of 49% (LL2) and 93% (A427) in tumor development and prolongations of 48% (LL2) in life expectancy. In the human model, more than 80% of the treated tumors disappeared or shrunk. Autoradiographic analysis of the treated sectioned tissue revealed the intratumoral distribution of the radioisotopes, and histological analysis showed corresponding areas of necrosis. In vitro experiments demonstrated a dose-dependent killing of tumors cells exposed to alpha particles. Conclusions: Short-lived diffusing alpha-emitters produced tumor growth retardation and increased survival in mice bearing lung tumor implants. These results justify further investigations with improved dose distributions.

Infrared Line Intensities for Formaldehyde from Simultaneous Measurements in the Infrared and Far Infrared Spectral Ranges

Science.gov (United States)

Fissiaux, L.; Földes, T.; Tchana, F. Kwabia; Daumont, L.; Lepère, M.; Vander Auwera, J.

2011-06-01

Formaldehyde (H_2CO) is an important intermediate compound in the degradation of the volatile organic compounds (VOCs), including methane, in the terrestrial troposphere. Its observation using optical remote sensing in the infrared range relies on the 3.6 and 5.7 μm absorption bands. Band and individual line intensities have been reported in both ranges. With the present work, we aim to also derive infrared line intensities for formaldehyde, however relying on pure rotation line intensities and the known electric dipole moment to determine the particle density. Indeed, because formaldehyde polymerizes or degrades easily, the gas phase may contain polymerization or degradation products. Spectra of H_2CO diluted in 10 hPa of N_2 were therefore simultaneously recorded in the 20-60 Cm-1 and 3.6 μm ranges, respectively using a Bruker IFS125HR Fourier transform spectrometer and a tunable diode laser. see A. Perrin, D. Jacquemart, F. Kwabia Tchana, N. Lacome, J. Quant. Spectrosc. Radiat. Transfer 110 (2009) 700-716, and references therein

High-grade soft tissue sarcoma arising in a desmoid tumor: case report and review of the literature.

Science.gov (United States)

Bertucci, François; Faure, Marjorie; Ghigna, Maria-Rosa; Chetaille, Bruno; Guiramand, Jérôme; Moureau-Zabotto, Laurence; Sarran, Anthony; Perrot, Delphine

2015-01-01

Desmoid tumors are rare benign monoclonal fibroblastic tumors. Their aggressiveness is local with no potential for metastasis or dedifferentiation. Here we report on a 61-year-old patient who presented a locally advanced breast desmoid tumor diagnosed 20 years after post-operative radiotherapy for breast carcinoma. After 2 years of medical treatment, a high-grade undifferentiated pleomorphic soft tissue sarcoma arose within the desmoid tumor. Despite extensive surgery removing both tumors, the patient showed locoregional relapse by the sarcoma, followed by multimetastatic progression, then death 25 months after the surgery. The arising of a soft tissue sarcoma in a desmoid tumor is an exceptional event since our case is the fourth one reported so far in literature. It reinforces the need for timely and accurate diagnosis when a new mass develops in the region of a preexisting desmoid tumor, and more generally when a desmoid tumor modifies its clinical or radiological aspect.

The anti-tumor effect of the quinoline-3-carboxamide tasquinimod: blockade of recruitment of CD11b+ Ly6Chi cells to tumor tissue reduces tumor growth

International Nuclear Information System (INIS)

Deronic, Adnan; Leanderson, Tomas; Ivars, Fredrik

2016-01-01

Previous work has demonstrated immunomodulatory, anti-tumor, anti-metastatic and anti-angiogenic effects of the small molecule quinoline-3-carboxamide tasquinimod in pre-clinical cancer models. To better understand the anti-tumor effects of tasquinimod in transplantable tumor models, we have evaluated the impact of the compound both on recruitment of myeloid cells to tumor tissue and on tumor-induced myeloid cell expansion as these cells are known to promote tumor development. Mice bearing subcutaneous 4 T1 mammary carcinoma tumors were treated with tasquinimod in the drinking water. A BrdU-based flow cytometry assay was utilized to assess the impact of short-term tasquinimod treatment on myeloid cell recruitment to tumors. Additionally, long-term treatment was performed to study the anti-tumor effect of tasquinimod as well as its effects on splenic myeloid cells and their progenitors. Myeloid cell populations were also immune-depleted by in vivo antibody treatment. Short-term tasquinimod treatment did not influence the proliferation of splenic Ly6C hi and Ly6G hi cells, but instead reduced the influx of Ly6C hi cells to the tumor. Treatment with tasquinimod for various periods of time after tumor inoculation revealed that the anti-tumor effect of this compound mainly operated during the first few days of tumor growth. Similar to tasquinimod treatment, antibody-mediated depletion of Ly6C hi cells within that same time frame, caused reduced tumor growth, thereby confirming a significant role for these cells in tumor development. Additionally, long-term tasquinimod treatment reduced the splenomegaly and expansion of splenic myeloid cells during a later phase of tumor development. In this phase, tasquinimod normalized the tumor-induced alterations in myeloerythroid progenitor cells in the spleen but had only limited impact on the same populations in the bone marrow. Our results indicate that tasquinimod treatment reduces tumor growth by operating early after tumor

Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

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Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

2017-11-15

Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. 1 H magnetic resonance spectroscopy ( 1 H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. 1 H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional

Concurrent Longitudinal EPR Monitoring of Tissue Oxygenation, Acidosis, and Reducing Capacity in Mouse Xenograft Tumor Models.

Science.gov (United States)

Bobko, Andrey A; Evans, Jason; Denko, Nicholas C; Khramtsov, Valery V

2017-06-01

Tissue oxygenation, extracellular acidity, and tissue reducing capacity are among crucial parameters of tumor microenvironment (TME) of significant importance for tumor pathophysiology. In this paper, we demonstrate the complementary application of particulate lithium octa-n-butoxy-naphthalocyanine and soluble nitroxide paramagnetic probes for monitoring of these TME parameters using electron paramagnetic resonance (EPR) technique. Two different types of therapeutic interventions were studied: hypothermia and systemic administration of metabolically active drug. In summary, the results demonstrate the utility of EPR technique for non-invasive concurrent longitudinal monitoring of physiologically relevant chemical parameters of TME in mouse xenograft tumor models, including that under therapeutic intervention.

Whole-tumor apparent diffusion coefficient (ADC) histogram analysis to differentiate benign peripheral neurogenic tumors from soft tissue sarcomas.

Science.gov (United States)

Nakajo, Masanori; Fukukura, Yoshihiko; Hakamada, Hiroto; Yoneyama, Tomohide; Kamimura, Kiyohisa; Nagano, Satoshi; Nakajo, Masayuki; Yoshiura, Takashi

2018-02-22

Apparent diffusion coefficient (ADC) histogram analyses have been used to differentiate tumor grades and predict therapeutic responses in various anatomic sites with moderate success. To determine the ability of diffusion-weighted imaging (DWI) with a whole-tumor ADC histogram analysis to differentiate benign peripheral neurogenic tumors (BPNTs) from soft tissue sarcomas (STSs). Retrospective study, single institution. In all, 25 BPNTs and 31 STSs. Two-b value DWI (b-values = 0, 1000s/mm 2 ) was at 3.0T. The histogram parameters of whole-tumor for ADC were calculated by two radiologists and compared between BPNTs and STSs. Nonparametric tests were performed for comparisons between BPNTs and STSs. P histogram parameters except kurtosis and entropy differed significantly between BPNTs and STSs. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Chemical derivation to enhance the chemical/oxidative stability of resorcinol-formaldehyde (R-F) resin

International Nuclear Information System (INIS)

Hubler, T.L.; Shaw, W.J.; Brown, G.N.; Linehan, J.C.; Franz, J.A.; Hart, T.R.; Hogan, M.O.

1996-09-01

Tank wastes at Hanford and SRS contain highly alkaline supernate solutions of conc. Na, K nitrates with large amounts of 137 Cs. It is desirable to remove and concentrate the highly radioactive fraction for vitrification. One candidate ion exchange material for removing the radiocesium is R-F resin. This report summarizes studies into synthesis and characterization of 4-derivatized R-F resins prepared in pursuit of more chemically/oxidatively robust resin. 85% 4-fluororesorcinol/15% phenol formaldehyde resin appears to have good stability in alkaline solution, although there may be some nucleophilic displacement reaction during synthesis; further studies are needed

Chondro-osseous differentiation in fat tissue tumors: magnetic resonance imaging with pathological correlation

International Nuclear Information System (INIS)

Orui, Hiroshi; Ishikawa, Akira; Tsuchiya, Takashi; Takahara, Masatoshi; Ogino, Toshihiko; Ito, Masafumi

2000-01-01

Chondro-osseous differentiation of three benign or malignant fat tissue tumors - two chondrolipomas and a liposarcoma with cartilaginous metaplasia - was studied with magnetic resonance (MR) imaging and compared with their pathological findings. The results suggest that demarcation of cartilage tisssue can be clearly defined on MR imaging when the size of the cartilaginous area is large. Myxoid matrix, degenerative fat tissue and lipodystrophic change may decrease the delineation of the cartilage tissue. (orig.)

Chondro-osseous differentiation in fat tissue tumors: magnetic resonance imaging with pathological correlation

Energy Technology Data Exchange (ETDEWEB)

Orui, Hiroshi; Ishikawa, Akira; Tsuchiya, Takashi; Takahara, Masatoshi; Ogino, Toshihiko [Dept. of Orthopaedic Surgery, Yamagata University School of Medicine (Japan); Ito, Masafumi [1. Dept. of Pathology, Yamagata University School of Medicine, Yamagata (Japan)

2000-08-01

Chondro-osseous differentiation of three benign or malignant fat tissue tumors - two chondrolipomas and a liposarcoma with cartilaginous metaplasia - was studied with magnetic resonance (MR) imaging and compared with their pathological findings. The results suggest that demarcation of cartilage tisssue can be clearly defined on MR imaging when the size of the cartilaginous area is large. Myxoid matrix, degenerative fat tissue and lipodystrophic change may decrease the delineation of the cartilage tissue. (orig.)

Development of lutetium-labeled bombesin derivates: relationship between structure and diagnostic-therapeutic activity for prostate tumor

International Nuclear Information System (INIS)

Pujatti, Priscilla Brunelli

2009-01-01

Bombesin (BBN) receptors - in particular, the gastrin-releasing peptide (GRP) receptor peptide - have been shown to be massively over expressed in several human tumors types, including prostate cancer, and could be an alternative as target for its treatment by radionuclide therapy (RNT). A large number of BBN analogs had already been synthesized for this purpose and have shown to reduce tumor growth in mice. Nevertheless, most of the studied analogs exhibit high abdominal accumulation, especially in pancreas. This abdominal accumulation may represent a problem in clinical use of radiolabeled bombesin analogs probably due to serious side effects to patients. The goal of the present work was to radiolabel a novel series of bombesin derivatives with lutetium-177 and to evaluate the relationship between their structure and diagnostic-therapeutic activity for prostate tumor. The generic structure of studied peptides is DOTA-Phe-(Gly) n -BBN(6-14), where DOTA is the chelator, n is the number of glycine amino acids of Phe-(Gly) n spacer and BBN(6-14) is the bombesin sequence from the amino acid 6 to the amino acid 14. Preliminary studies were done to establish the ideal labeling conditions for obtaining the highest yield of labeled bombesin derivatives, determined by instant thin layer chromatography (ITLC-SG) and high performance liquid chromatography (HPLC). The stability of the preparations was evaluated either after storing at 2-8 degree C or incubation in human serum at 37 degree C and the partition coefficient was determined in n:octanol:water. In vivo studies were performed in both healthy Balb-c and Nude mice bearing PC-3 xenografts, in order to characterize the biological properties of labeled peptides. In vitro studies involved the evaluation of cold bombesin derivatives effect in PC-3 cells proliferation. Bombesin derivatives were successfully labeled with high yield at optimized conditions and exhibited high stability at 4 degree C. The analysis of the

Experimental study on active specific immunotherapy utilizing the immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 3

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Imanaka, Kazufumi; Gose, Kyuhei; Imajo, Yoshinari; Kimura, Shuji

1982-01-01

We have already demonstrated the remarkable effect of the active specific immunotherapy utilizing tumor cells and infiltrating lymphocytes prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the active specific immunotherapy using the tumor cells and infiltrating lymphocytes which were cryopreserved at -196 0 C in liquid nitrogen was investigated in female C3H/He mice inoculated MM46 tumor. Irradiation with the dose of 3,000 rads was performed on the sixth day. The tumor cells and lymphocytes which were separated from 2,000 rads-irradiated tumor tissue were frozen by the program freezer to be preserved at -196 0 C for two months and were thawed to inject into the tumor-bearing mice on the thirteenth day. Anti-tumor effect was evaluated by the regression of the tumor and survival curves. The remarkable regression of the tumor (p < 0.01) and significant elongation of the survival period (p < 0.1) were observed in the group which received the active specific immunotherapy using the cryopreserved tumor cells and lymphocytes as well as the group using the fresh tumor cells and lymphocytes prepared from a low-dose irradiated tumor tissue. (author)

A survey of formaldehyde in the Cepheus OB3 molecular cloud

International Nuclear Information System (INIS)

Few, R.W.; Cohen, R.J.

1983-01-01

The 1 11 - 1 10 absorption line of formaldehyde at 6-cm wavelength has been surveyed over the region of the Cepheus OB3 molecular cloud, using the Jodrell Bank Mk II radio telescope (beamwidth 9 x 10 arcmin 2 ). The measurements have a velocity resolution of 0.27 km s - 1 and an rms noise level of approx. 0.01 K. The formaldehyde has a very clumpy distribution which is broadly similar to the CO distribution found by Sargent. A total molecular mass of 1.9 x 10 4 solar masses is implied by the formaldehyde measurements. Cepheus A is not the dominant concentration in the formaldehyde map. The most massive formaldehyde concentration is Cepheus C, which has a mass of 3600 solar masses. It appears to be stabilized by rotation. (author)

Teratogenic effect of formaldehyde in rabbits

Directory of Open Access Journals (Sweden)

A. A. Al–Saraj

2009-01-01

Full Text Available Thirty three pregnant rabbits were exposed to vapour of 10% formaldehyde (12 ppm throughout the gestation period to know its effect on newborns. The results showed no abortion or foetal mortality but there were some anomalies (23.8% among the newborns rabbits which includes: meromelia (6.8%, encephalocele (6.1%, Oligodactyly (4.1%, Umbilical hernia (3.4% and Short tail (3.4%; besides that small for date and decrease in the body weight of the newborns were also noticed. These findings suggest that formaldehyde is a teratogenic agent.

Tumor development in field-cancerized tissue is inhibited by a double application of Boron neutron capture therapy (BNCT) without exceeding radio-tolerance

International Nuclear Information System (INIS)

Monti Hughes, Andrea; Heber, Elisa M.; Itoiz, Maria E.; Molinari, Ana J.; Garabalino, Marcela A.; Trivillin, Veronica A.; Schwint, Amanda E.; Aromando, Romina F.

2009-01-01

Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of a 'single' application of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-1(Na 2 10 B 10 H 10 ) or (GB-10+BPA) to treat hamster cheek pouch tumors with no normal tissue radiotoxicity. Based on these results, we developed a model of precancerous tissue in the hamster cheek pouch for long-term studies. Employing this model we evaluated the long-term potential inhibitory effect on the development of second primary tumors from precancerous tissue and eventual radiotoxicity of a single application of BNCT mediated by BPA, GB-10 or (GB-10+BPA), in the RA-6. The clinical rationale of this study was to search for a BNCT protocol that is therapeutic for tumor, not radio-toxic for the normal tissue that lies in the neutron beam path, and exerts the desired inhibitory effect on the development of second primary tumors, without exceeding the radio-tolerance of precancerous tissue, the dose limiting tissue in this case. Second primary tumors that arise in precancerous tissue (also called locoregional recurrences) are a frequent cause of therapeutic failure in head and neck tumors. Aim: Evaluate the radiotoxicity and inhibitory effect of a 'double' application of the same BNCT protocols that were proved therapeutically successful for tumor and precancerous tissue, with a long term follow up (8 months). A 'double' application of BNCT is a potentially useful strategy for the treatment of tumors, in particular the larger ones, but the cost in terms of side-effects in dose-limiting tissues might preclude its application and requires cautious evaluation. Materials and methods: We performed a double application of 1) BPA-BNCT; 2) (GB

Conditioned Media from Human Adipose Tissue-Derived Mesenchymal Stem Cells and Umbilical Cord-Derived Mesenchymal Stem Cells Efficiently Induced the Apoptosis and Differentiation in Human Glioma Cell Lines In Vitro

Directory of Open Access Journals (Sweden)

Chao Yang

2014-01-01

Full Text Available Human mesenchymal stem cells (MSCs have an intrinsic property for homing towards tumor sites and can be used as tumor-tropic vectors for tumor therapy. But very limited studies investigated the antitumor properties of MSCs themselves. In this study we investigated the antiglioma properties of two easily accessible MSCs, namely, human adipose tissue-derived mesenchymal stem cells (ASCs and umbilical cord-derived mesenchymal stem cells (UC-MSCs. We found (1 MSC conditioned media can significantly inhibit the growth of human U251 glioma cell line; (2 MSC conditioned media can significantly induce apoptosis in human U251 cell line; (3 real-time PCR experiments showed significant upregulation of apoptotic genes of both caspase-3 and caspase-9 and significant downregulation of antiapoptotic genes such as survivin and XIAP after MSC conditioned media induction in U 251 cells; (4 furthermore, MSCs conditioned media culture induced rapid and complete differentiation in U251 cells. These results indicate MSCs can efficiently induce both apoptosis and differentiation in U251 human glioma cell line. Whereas UC-MSCs are more efficient for apoptosis induction than ASCs, their capability of differentiation induction is not distinguishable from each other. Our findings suggest MSCs themselves have favorable antitumor characteristics and should be further explored in future glioma therapy.

Contact allergic dermatitis from melamine formaldehyde resins in a patient with a negative patch-test reaction to formaldehyde.

Science.gov (United States)

García Gavin, Juan; Loureiro Martinez, Manuel; Fernandez-Redondo, Virginia; Seoane, Maria-José; Toribio, Jaime

2008-01-01

Melamine paper is a basic material used in the furniture industry for home and office interiors. Contact allergic dermatitis from melamine formaldehyde resins (MFRs) should be considered in patients who work on melamine paper impregnation lines. We report a case of a 28-year-old female plywood worker who developed eczema on the dorsal side of her hands and wrists after 2 years of working on the melamine paper impregnation line. She had a relevant positive patch-test reaction to MFR, with a negative reaction to formaldehyde. Contact dermatitis due to MFR is not common, and it is usually related to products that are not fully cured or to close contact with intermediate products on the assembly line. Formaldehyde release from MFR can explain most of the positive responses. To our knowledge, this is the first report of MFR contact allergic dermatitis in a worker on a melamine paper impregnation line.

Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure

NARCIS (Netherlands)

Oedayrajsingh-Varma, M. J.; van Ham, S. M.; Knippenberg, M.; Helder, M. N.; Klein-Nulend, J.; Schouten, T. E.; Ritt, M. J. P. F.; van Milligen, F. J.

2006-01-01

Adipose tissue contains a stromal vascular fraction that can be easily isolated and provides a rich source of adipose tissue-derived mesenchymal stem cells (ASC). These ASC are a potential source of cells for tissue engineering. We studied whether the yield and growth characteristics of ASC were

Sol-gel based sensor for selective formaldehyde determination

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Bunkoed, Opas [Trace Analysis and Biosensor Research Center, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand); Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand); Davis, Frank [Cranfield Health, Cranfield University, Bedford MK43 0AL (United Kingdom); Kanatharana, Proespichaya, E-mail: proespichaya.K@psu.ac.th [Trace Analysis and Biosensor Research Center, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand); Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand); Thavarungkul, Panote [Trace Analysis and Biosensor Research Center, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand); Department of Physics, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112 (Thailand); Higson, Seamus P.J., E-mail: s.p.j.higson@cranfield.ac.uk [Cranfield Health, Cranfield University, Bedford MK43 0AL (United Kingdom)

2010-02-05

We report the development of transparent sol-gels with entrapped sensitive and selective reagents for the detection of formaldehyde. The sampling method is based on the adsorption of formaldehyde from the air and reaction with {beta}-diketones (for example acetylacetone) in a sol-gel matrix to produce a yellow product, lutidine, which was detected directly. The proposed method does not require preparation of samples prior to analysis and allows both screening by visual detection and quantitative measurement by simple spectrophotometry. The detection limit of 0.03 ppmv formaldehyde is reported which is lower than the maximum exposure concentrations recommended by both the World Health Organisation (WHO) and the Occupational Safety and Health Administration (OSHA). This sampling method was found to give good reproducibility, the relative standard deviation at 0.2 and 1 ppmv being 6.3% and 4.6%, respectively. Other carbonyl compounds i.e. acetaldehyde, benzaldehyde, acetone and butanone do not interfere with this analytical approach. Results are provided for the determination of formaldehyde in indoor air.

Sol-gel based sensor for selective formaldehyde determination

International Nuclear Information System (INIS)

Bunkoed, Opas; Davis, Frank; Kanatharana, Proespichaya; Thavarungkul, Panote; Higson, Seamus P.J.

2010-01-01

We report the development of transparent sol-gels with entrapped sensitive and selective reagents for the detection of formaldehyde. The sampling method is based on the adsorption of formaldehyde from the air and reaction with β-diketones (for example acetylacetone) in a sol-gel matrix to produce a yellow product, lutidine, which was detected directly. The proposed method does not require preparation of samples prior to analysis and allows both screening by visual detection and quantitative measurement by simple spectrophotometry. The detection limit of 0.03 ppmv formaldehyde is reported which is lower than the maximum exposure concentrations recommended by both the World Health Organisation (WHO) and the Occupational Safety and Health Administration (OSHA). This sampling method was found to give good reproducibility, the relative standard deviation at 0.2 and 1 ppmv being 6.3% and 4.6%, respectively. Other carbonyl compounds i.e. acetaldehyde, benzaldehyde, acetone and butanone do not interfere with this analytical approach. Results are provided for the determination of formaldehyde in indoor air.

Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

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Jin Qi

2017-08-01

Full Text Available Background/Aims: Mesenchymal stem/stromal cells (MSCs are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. Methods: MSCs derived from human bone marrow (hBMSCs were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63 and gastric cancer (SGC7901 cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. Results: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. Conclusion: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.

High CD49f expression is associated with osteosarcoma tumor progression: a study using patient-derived primary cell cultures.

Science.gov (United States)

Penfornis, Patrice; Cai, David Z; Harris, Michael R; Walker, Ryan; Licini, David; Fernandes, Joseph D A; Orr, Griffin; Koganti, Tejaswi; Hicks, Chindo; Induru, Spandana; Meyer, Mark S; Khokha, Rama; Barr, Jennifer; Pochampally, Radhika R

2014-08-01

Overall prognosis for osteosarcoma (OS) is poor despite aggressive treatment options. Limited access to primary tumors, technical challenges in processing OS tissues, and the lack of well-characterized primary cell cultures has hindered our ability to fully understand the properties of OS tumor initiation and progression. In this study, we have isolated and characterized cell cultures derived from four central high-grade human OS samples. Furthermore, we used the cell cultures to study the role of CD49f in OS progression. Recent studies have implicated CD49f in stemness and multipotency of both cancer stem cells and mesenchymal stem cells. Therefore, we investigated the role of CD49f in osteosarcomagenesis. First, single cell suspensions of tumor biopsies were subcultured and characterized for cell surface marker expression. Next, we characterized the growth and differentiation properties, sensitivity to chemotherapy drugs, and anchorage-independent growth. Xenograft assays showed that cell populations expressing CD49f(hi) /CD90(lo) cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49f(hi) /CD90(lo) cell population is generating more aggressive OS tumor growth and indicating this cell surface marker could be a potential candidate for the isolation of an aggressive cell type in OSs. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Soft-tissue reactions following irradiation of primary brain and pituitary tumors

International Nuclear Information System (INIS)

Baglan, R.J.; Marks, J.E.

1981-01-01

One hundred and ninety-nine patients who received radiation therapy for a primary brain or pituitary tumor were studied for radiation-induced soft-tissue reactions of the cranium, scalp, ears and jaw. The frequency of these reactions was studied as a function of: the radiation dose 5 mm below the skin surface, dose distribution, field size and fraction size. Forty percent of patients had complete and permanent epilation, while 21% had some other soft-tissue complication, including: scalp swelling-6%, external otitis-6%, otitis media-5%, ear swelling-4%, etc. The frequency of soft-tissue reactions correlates directly with the radiation dose at 5 mm below the skin surface. Patients treated with small portals ( 2 ) had few soft-tissue reactions. The dose to superficial tissues, and hence the frequency of soft-tissue reactions can be reduced by: (1) using high-energy megavoltage beams; (2) using equal loading of beams; and (3) possibly avoiding the use of electron beams

Mesenchymal stem cells derived from adipose tissue vs bone marrow: in vitro comparison of their tropism towards gliomas.

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Courtney Pendleton

Full Text Available INTRODUCTION: Glioblastoma is the most common primary malignant brain tumor, and is refractory to surgical resection, radiation, and chemotherapy. Human mesenchymal stem cells (hMSC may be harvested from bone marrow (BMSC and adipose (AMSC tissue. These cells are a promising avenue of investigation for the delivery of adjuvant therapies. Despite extensive research into putative mechanisms for the tumor tropism of MSCs, there remains no direct comparison of the efficacy and specificity of AMSC and BMSC tropism towards glioma. METHODS: Under an IRB-approved protocol, intraoperative human Adipose MSCs (hAMSCs were established and characterized for cell surface markers of mesenchymal stem cell origin in conjunction with the potential for tri-lineage differentiation (adipogenic, chondrogenic, and osteogenic. Validated experimental hAMSCs were compared to commercially derived hBMSCs (Lonza and hAMSCs (Invitrogen for growth responsiveness and glioma tropism in response to glioma conditioned media obtained from primary glioma neurosphere cultures. RESULTS: Commercial and primary culture AMSCs and commercial BMSCs demonstrated no statistically significant difference in their migration towards glioma conditioned media in vitro. There was statistically significant difference in the proliferation rate of both commercial AMSCs and BMSCs as compared to primary culture AMSCs, suggesting primary cultures have a slower growth rate than commercially available cell lines. CONCLUSIONS: Adipose- and bone marrow-derived mesenchymal stem cells have similar in vitro glioma tropism. Given the well-documented ability to harvest larger numbers of AMSCs under local anesthesia, adipose tissue may provide a more efficient source of MSCs for research and clinical applications, while minimizing patient morbidity during cell harvesting.

Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

Science.gov (United States)

Zhao, Hongyun; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Bernard, Vincent; Moss, Tyler; Marini, Juan C; Tudawe, Thavisha; Seviour, Elena G; San Lucas, F Anthony; Alvarez, Hector; Gupta, Sonal; Maiti, Sourindra N; Cooper, Laurence; Peehl, Donna; Ram, Prahlad T; Maitra, Anirban; Nagrath, Deepak

2016-01-01

Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions. DOI: http://dx.doi.org/10.7554/eLife.10250.001 PMID:26920219

  Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

DEFF Research Database (Denmark)

Rasmussen, Anne-Sofie Schrohl; Look, Maxime P.; Meijer-van Gelder, Marion E.

tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however...... Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006......) suggesting that TIMP-1 may be a predictive marker in breast cancer patients. Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen. Patients...

Migration of formaldehyde from melamine-ware: UK 2008 survey results.

Science.gov (United States)

Potter, E L J; Bradley, E L; Davies, C R; Barnes, K A; Castle, L

2010-06-01

Fifty melamine-ware articles were tested for the migration of formaldehyde - with hexamethylenetetramine (HMTA) expressed as formaldehyde - to see whether the total specific migration limit (SML(T)) was being observed. The SML(T), given in European Commission Directive 2002/72/EC as amended, is 15 mg kg(-1). Fourier transform-infrared (FT-IR) spectroscopy was carried out on the articles to confirm the plastic type. Articles were exposed to the food simulant 3% (w/v) aqueous acetic acid under conditions representing their worst foreseeable use. Formaldehyde and HMTA in food simulants were determined by a spectrophotometric derivatization procedure. Positive samples were confirmed by a second spectrophotometric procedure using an alternative derivatization agent. As all products purchased were intended for repeat use, three sequential exposures to the simulant were carried out. Formaldehyde was detected in the simulant exposed to 43 samples. Most of the levels found were well below the limits set in law such that 84% of the samples tested were compliant. However, eight samples had formaldehyde levels that were clearly above the legal maximum at six to 65 times the SML(T).

Computerized tomography in bone and soft tissue tumors

International Nuclear Information System (INIS)

Isobe, Yasushi; Kaneta, Koichi; Kawaguchi, Tomoyoshi; Wada, Shigehito; Matsumoto, Seiichi

1982-01-01

The contribution to pretreatment evaluation and surgical planning of 238 CT image of bone and soft tissue lesions was evaluated. Their accuracy was studied by careful postoperative examination of gross surgical specimens and histologic sections. CT was helpful in delineating the anatomic extent of lesions and, therefore, in planning the appropriate resection. CT was of little help in confirming or detecting residual or recurrent tumor after prior resection. CT was not accurate or helpful in distinguishing benign from malignant lesions when the clinical presentation and roentgenographic findings were confusing. (author)

Computerized tomography in bone and soft tissue tumors

Energy Technology Data Exchange (ETDEWEB)

Isobe, Yasushi; Kaneta, Koichi; Kawaguchi, Tomoyoshi; Wada, Shigehito; Matsumoto, Seiichi (Japanese Foundation for Cancer Research, Tokyo. Hospital)

1982-11-01

The contribution to pretreatment evaluation and surgical planning of 238 CT image of bone and soft tissue lesions was evaluated. Their accuracy was studied by careful postoperative examination of gross surgical specimens and histologic sections. CT was helpful in delineating the anatomic extent of lesions and, therefore, in planning the appropriate resection. CT was of little help in confirming or detecting residual or recurrent tumor after prior resection. CT was not accurate or helpful in distinguishing benign from malignant lesions when the clinical presentation and roentgenographic findings were confusing.

Diffusion-weighted imaging of tumor recurrencies and posttherapeutical soft-tissue changes in humans

International Nuclear Information System (INIS)

Baur, A.; Huber, A.; Reiser, M.; Arbogast, S.; Duerr, H.R.; Zysk, S.; Wendtner, C.; Deimling, M.

2001-01-01

The aim of this study was to examine soft tissue tumor recurrences and posttherapeutic soft tissue changes in humans with a diffusion-weighted steady-state free precession (SSFP) sequence. Twenty-four patients with 29 pathologies of the pelvis or the extremities were examined. The lesions were classified as follows: group 1, recurrent viable tumors (n = 10); group 2, postoperative hygromas (n = 7); and group 3, posttherapeutic reactive inflammatory muscle changes (n = 12). The sequence protocol in these patients consisted of short tau inversion recovery images, T2-weighted spin-echo (SE), pre- and postcontrast T1-weighted SE images and the diffusion-weighted SSFP sequence. The signal loss on diffusion-weighting was evaluated visually on a four-grade scale and quantitatively. The signal intensities were measured in regions of interest and a regression analysis was performed. Statistical analyses was performed utilizing the Student's t-test. The signal loss was significantly higher for hygromas and edematous muscle changes than for recurrent tumors (p < 0.001) indicating higher diffusion of water protons. The regression coefficient was -0.11 (mean) for tumors. Hygromas had a significantly higher signal loss than inflammatory edematous muscle changes (p < 0.01). The regression coefficients were -0.29 (mean) for hygromas and -0.22 (mean) for edematous muscle changes. The SSFP sequence seems to be a suitable method for diffusion-weighted imaging of the musculoskeletal system in humans. These preliminary results suggest that the signal loss and the regression coefficients can be used to characterize different types of tissue. (orig.)

A Rare Cutaneous Adnexal Tumor: Malignant Proliferating Trichilemmal Tumor

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Omer Alici

2015-01-01

Full Text Available Proliferating trichilemmal tumors (PTTs are neoplasms derived from the outer root sheath of the hair follicle. These tumors, which commonly affect the scalp of elderly women, rarely demonstrate malignant transformation. Although invasion of the tumors into neighboring tissues and being accompanied with anaplasia and necrosis are accepted as findings of malignancy, histological features may not always be sufficient to identify these tumors. The clinical behavior of the tumor may be incompatible with its histological characteristics. Squamous-cell carcinoma should certainly be considered in differential diagnosis because of its similarity in morphological appearance with PTT. Immunostaining for CD34, P53, and Ki-67 is a useful adjuvant diagnostic method that can be used in differential diagnosis aside from morphological findings. In this study, we aimed to present the case of a 52-year-old female patient with clinicopathological features. We reported a low-grade malignant proliferating trichilemmal tumor in this patient and detected no relapse or metastasis in a 24-month period of follow-up.

Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

Science.gov (United States)

Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

2013-02-01

Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

On clinical usefulness of Tl-201 scintigraphy for the management of malignant soft tissue tumors

International Nuclear Information System (INIS)

Terui, Shoji; Terauchi, Takashi; Abe, Hiroyuki; Fukuma, Hisatoshi; Beppu, Yasuo; Chuman, Koichi; Yokoyama, Ryohei

1994-01-01

The purpose of this study was to investigate Tl-201 as a tumor scanning agent in patients with malignant soft tissue sarcomas and to establish the sensitivity of this type of scintigraphy concerning local recurrences or metastases that may remain clinically suspected. Seventy-eight patients with malignant soft tissue sarcomas and 22 with benign soft tissue tumors were studied. Of these 78 malignant soft tissue sarcomas patients, the sensitivity of Tl-201 (81.2%) was higher than that of Ga-67 (68.8%). Thirty-three out of 78 patients received a total of 95 consecutive scintigraphic follow-up examinations. Therapeutic effects was assessed by comparing the results of Tl-201 examinations with the clinical findings. Of these 33 patients, the therapeutic effects observed were as follows: complete remission 1, partial remission 8, progress of disease 1, and no remarkable change 23. Tl-201 scintigraphy has proved itself very useful not only in clinically detecting the malignant soft tissue sarcomas and in assessing therapeutic effects on these diseases, but also in assessing the follow-up patients with malignant soft tissue sarcomas. (author)

Performance of optical biosensor using alcohol oxidase enzyme for formaldehyde detection

Science.gov (United States)

Sari, A. P.; Rachim, A.; Nurlely, Fauzia, V.

2017-07-01

The recent issue in the world is the long exposure of formaldehyde which is can increase the risk of human health, therefore, that is very important to develop a device and method that can be optimized to detect the formaldehyde elements accurately, have a long lifetime and can be fabricated and produced in large quantities. A new and simple prepared optical biosensor for detection of formaldehyde in aqueous solutions using alcohol oxidase (AOX) enzyme was successfully fabricated. The poly-n-butyl acrylic-co-N-acryloxysuccinimide (nBA-NAS) membranes containing chromoionophore ETH5294 were used for immobilization of alcohol oxidase enzyme (AOX). Biosensor response was based on the colour change of chromoionophore as a result of enzymatic oxidation of formaldehyde and correlated with the detection concentration of formaldehyde. The performance of biosensor parameters were measured through the optical absorption value using UV-Vis spectrophotometer including the repeatability, reproducibility, selectivity and lifetime. The results showed that the prepared biosensor has good repeatability (RSD = 1.9 %) and good reproducibility (RSD = 2.1 %). The biosensor was selective formaldehyde with no disturbance by methanol, ethanol, and acetaldehyde, and also stable before 49 days and decrease by 41.77 % after 49 days.

THE PHOTODISSOCIATION OF FORMALDEHYDE IN COMETS

Energy Technology Data Exchange (ETDEWEB)

Feldman, Paul D., E-mail: pfeldman@jhu.edu [Department of Physics and Astronomy, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218 (United States)

2015-10-20

Observations of comets in the 905–1180 Å spectral band made with the Far Ultraviolet Spectroscopic Explorer in 2001 and 2004 show unusual features in the fluorescent emissions of CO and H{sub 2}. These include emission from a non-thermal high-J rotational population of CO and solar Lyα induced fluorescence from excited vibrational levels of H{sub 2}, both of which are attributed to the photodissociation of formaldehyde. In this paper we model the large number of observed H{sub 2} lines and demonstrate the dependence of the pumping on the heliocentric velocity of the comet and the solar line profiles. We also derive the rotational and vibrational populations of H{sub 2} and show that they are consistent with the results of laboratory studies of the photodissociation of H{sub 2}CO. In addition to the principal series of H i and O i, the residual spectrum is found to consist mainly of the Rydberg series of C i multiplets from which we derive the mean carbon column abundance in the coma. Fluorescent emissions from N i and N{sub 2} are also searched for.

A Formaldehyde Exposure Assessment Tool for Occupants of FEMA Temporary Housing Units

Energy Technology Data Exchange (ETDEWEB)

Parthasarathy, Srinandini; Spears, Michael; Maddalena, Randy L.; Russell, Marion L; Apte, Michael G.

2010-10-01

The report outlines the methodology used to develop a web-based tool to assess the formaldehyde exposure of the occupants of Federal Emergency Management Administration (FEMA) temporary housing units (THUs) after Hurricanes Katrina and Rita in 2005. Linear regression models were built using available data to retrospectively estimate the indoor temperature and relative humidity, formaldehyde emission factors and concentration, and hence the formaldehyde exposures. The interactive web-tool allows the user to define the inputs to the model to evaluate formaldehyde exposures for different scenarios.

Immunocytochemistry of formalin-fixed human brain tissues: microwave irradiation of free-floating sections.

Science.gov (United States)

Shiurba, R A; Spooner, E T; Ishiguro, K; Takahashi, M; Yoshida, R; Wheelock, T R; Imahori, K; Cataldo, A M; Nixon, R A

1998-01-01

Formalin fixation, the chemical process in which formaldehyde binds to cells and tissues, is widely used to preserve human brain specimens from autolytic decomposition. Ultrastructure of cellular and mitochondrial membranes is markedly altered by vesiculation, but this does not interfere with diagnostic evaluation of neurohistology by light microscopy. Serious difficulties are encountered, however, when immunocytochemical staining is attempted. Antigens that are immunoreactive in unfixed frozen sections and protein extracts appear to be concealed or destroyed in formalin-fixed tissues. In dilute aqueous solution, formaldehyde is in equilibrium with methylene glycol and its polymeric hydrates, the balance by far in favor of methylene glyco. Carbonylic formaldehyde is a reactive electrophilic species well known for crosslinking functional groups in tissue proteins, nucleic acids, and polysaccharides. Some of its methylene crosslinks are readily hydrolyzed. Others are stable and irreversible. During immunostaining reactions, intra- and inter-molecular links between macromolecules limit antibody permeation of tissue sections, alter protein secondary structure, and reduce accessibility of antigenic determinants . Accordingly, immunoreactivity is diminished for many antigens. Tissues are rapidly penetrated by methylene glycol, but formaldehyde binding to cellular constituents is relatively slow, increasing progressively until equilibrium is reached. In addition, prolonged storage in formalin may result in acidification of human brain specimens. Low pH favors dissociation of methylene glycol into formaldehyde, further reducing both classical staining and antigen detectability. Various procedures have been devised to counter the antigen masking effects of formaldehyde. Examples include pretreatment of tissue sections with proteases, formic acid, or ultrasound. Recently, heating of mounted sections in ionic salt solution by microwave energy was found to restore many

Imaging appearances of soft-tissue tumors of the pediatric foot: review of a 15-year experience at a tertiary pediatric hospital

Energy Technology Data Exchange (ETDEWEB)

Caro-Dominguez, Pablo [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); Hospital San Juan de Dios, Health Time Group, Department of Diagnostic Imaging, Cordoba, Andalucia (Spain); Navarro, Oscar M. [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada)

2017-11-15

Tumors of the foot are rare in children. In this review the authors illustrate radiographic, sonographic and MR imaging findings of foot soft-tissue tumors in children based on all cases presenting at a tertiary pediatric hospital during the 15-year period of 1999-2014. Among these cases there were 155 tumors of the foot - 72 of the bones and 83 of the soft tissues. Vascular malformations, fibromatosis and sarcomas were respectively the most frequent benign, intermediate and malignant soft-tissue tumors. Some tumors showed specific imaging findings. In imaging investigations, ultrasound can be used as the first imaging modality for diagnostic workup of most lesions because it is noninvasive, low-cost and readily available, and can confirm the presence of the mass and evaluate cystic components, especially in young children who would otherwise require sedation for MR imaging. MR imaging is the reference standard technique because of its high tissue contrast, which allows for detection and characterization of soft-tissue and bone abnormalities. MR imaging is useful as the first imaging modality in select cases, including those with high suspicion of malignancy, very large lesions or pre-treatment lesions. Recognition of some typical imaging findings in pediatric soft-tissue foot tumors is helpful to establish diagnosis and facilitate patient management. (orig.)

Evaluation of Soft Tissue Sarcoma Tumors Electrical Conductivity Anisotropy Using Diffusion Tensor Imaging for Numerical Modeling on Electroporation

Directory of Open Access Journals (Sweden)

Ghazikhanlou-sani K.

2016-06-01

Full Text Available Introduction: There is many ways to assessing the electrical conductivity anisotropy of a tumor. Applying the values of tissue electrical conductivity anisotropy is crucial in numerical modeling of the electric and thermal field distribution in electroporation treatments. This study aims to calculate the tissues electrical conductivity anisotropy in patients with sarcoma tumors using diffusion tensor imaging technique. Materials and Method: A total of 3 subjects were involved in this study. All of patients had clinically apparent sarcoma tumors at the extremities. The T1, T2 and DTI images were performed using a 3-Tesla multi-coil, multi-channel MRI system. The fractional anisotropy (FA maps were performed using the FSL (FMRI software library software regarding the DTI images. The 3D matrix of the FA maps of each area (tumor, normal soft tissue and bone/s was reconstructed and the anisotropy matrix was calculated regarding to the FA values. Result: The mean FA values in direction of main axis in sarcoma tumors were ranged between 0.475–0.690. With assumption of isotropy of the electrical conductivity, the FA value of electrical conductivity at each X, Y and Z coordinate axes would be equal to 0.577. The gathered results showed that there is a mean error band of 20% in electrical conductivity, if the electrical conductivity anisotropy not concluded at the calculations. The comparison of FA values showed that there is a significant statistical difference between the mean FA value of tumor and normal soft tissues (P<0.05. Conclusion: DTI is a feasible technique for the assessment of electrical conductivity anisotropy of tissues. It is crucial to quantify the electrical conductivity anisotropy data of tissues for numerical modeling of electroporation treatments.

Diagnostic utility of NCOA2 fluorescence in situ hybridization and Stat6 immunohistochemistry staining for soft tissue angiofibroma and morphologically similar fibrovascular tumors.

Science.gov (United States)

Sugita, Shintaro; Aoyama, Tomoyuki; Kondo, Kei; Keira, Yoshiko; Ogino, Jiro; Nakanishi, Katsuya; Kaya, Mitsunori; Emori, Makoto; Tsukahara, Tomohide; Nakajima, Hisaya; Takagi, Masayuki; Hasegawa, Tadashi

2014-08-01

Soft tissue angiofibroma (STA), a recently suggested new histologic entity, is a benign fibrovascular soft tissue tumor composed of bland spindle-shaped tumor cells with abundant collagenous to myxoid stroma and branching small vessels. The lesion has a characteristic AHRR-NCOA2 fusion gene derived from chromosomal translocation of t(5;8)(p15;q13). However, morphologically similar tumors containing abundant fibrovascular and myxoid stroma can complicate diagnosis. We designed an original DNA probe for detecting NCOA2 split signals on fluorescence in situ hybridization (FISH) and estimated its utility with 20 fibrovascular tumors: 4 each of STAs, solitary fibrous tumors (SFTs), and cellular angiofibromas and 3 each of low-grade myxofibrosarcomas, myxoid liposarcomas, and low-grade fibromyxoid sarcomas. We also performed FISH for 13q14 deletion and immunohistochemistry (IHC) staining for estrogen receptor, progesterone receptor, retinoblastoma protein, and MUC-4 expression. Furthermore, IHC for Stat6 was conducted in the 20 cases analyzed by FISH and in an additional 26 SFTs. We found moderate to strong nuclear Stat6 expression in all SFTs but no expression in the other tumors. Both estrogen receptor and progesterone receptor expressions were observed in STAs, SFTs, and cellular angiofibromas. Expression of retinoblastoma protein was found in less than 10% of cells in all tumor types except myxoid liposarcoma. The low-grade fibromyxoid sarcomas were strongly positive for MUC-4. All STAs showed NCOA2 split signals on FISH. All tumors, regardless of histologic type, had 13q14 deletion. The NCOA2 FISH technique is a practical method for confirming STA diagnosis. The combination of NCOA2 FISH and Stat6 IHC proved effective for the differential diagnosis of STA, even when using small biopsy specimens. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of reuse and bleach/formaldehyde reprocessing on polysulfone and polyamide hemodialyzers.

Science.gov (United States)

Cornelius, Rena M; McClung, W Glenn; Barre, Paul; Esguerra, Fe; Brash, John L

2002-01-01

The surface features, morphology, and blood interactions of fibers from pristine, bleach/formaldehyde reprocessed, and reused Fresenius Polysulfone High Flux (Hemoflow F80B) hemodialyzers and Gambro Polyflux 21S Polyamide hemodialyzers have been studied. SEM images of fibers from both hemodialyzer types revealed a dense skin layer on the inner surface and a relatively thick porous layer on the outer surface. The 21S polyamide support layer consisted of interconnected highly porous structures. Environmental scanning electron microscopy and atomic force microscopy images of both membrane types showed alterations in morphology due to reprocessing and reuse; however the changes were more marked for the 21S polyamide dialyzers. Fluorescence microscopy images showed only minimal fluorescence associated with the fibers after patient use and reprocessing, suggesting that blood derived deposits were removed by processing. The protein layers formed on pristine and reused hemodialyzer membranes during clinical use were studied using SDS-PAGE and immunoblotting. Before bleach/formaldehyde treatment, protein layers of considerable amount and complexity were found on the blood side of singly and multiply used dialyzers. Proteins adsorbed on the dialysate side were predominantly in the molecular mass region below 30 kDa. However, some higher molecular mass proteins were detected on the dialysate side of the 21 S polyamide dialyzers. Very little protein was detected on dialyzers that were treated with bleach/formaldehyde after dialysis, regardless of whether they had been used/reprocessed once or 12 times.

Current concepts in non-gastrointestinal stromal tumor soft tissue sarcomas: A primer for radiologists

Energy Technology Data Exchange (ETDEWEB)

Baheti, Akahay D. [Dept. of Radiology, Tata Memorial Centre, Mumbai (India); Tirumani, Harika [Dept. of Radiology, University of Arkansas for Medical Sciences, Little Rock (United States); O' Neill, Alibhe; Jagannathan, Jyothi P. [Dept. of Imaging, Dana-Farber Cancer Institute, Boston (United States)

2017-01-15

Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist.

Current concepts in non-gastrointestinal stromal tumor soft tissue sarcomas: A primer for radiologists

International Nuclear Information System (INIS)

Baheti, Akahay D.; Tirumani, Harika; O'Neill, Alibhe; Jagannathan, Jyothi P.

2017-01-01

Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist

Evaluation of 18F-labeled icotinib derivatives as potential PET agents for tumor imaging

International Nuclear Information System (INIS)

Hongyu Ren; Hongyu Ning; Jin Chang; Mingxia Zhao; Yong He; Yan Chong; Chuanmin Qi

2016-01-01

In this study, three 18 F-labeled crown ether fused anilinoquinazoline derivatives ([ 18 F]11a-c) were synthesized and evaluated as potential tumor imaging probes. The biodistribution results of [ 18 F]11b were good. Compared with [ 18 F]-fludeoxyglucose and l-[ 18 F]-fluoroethyltyrosine in the same animal model, [ 18 F]11b had better tumor/brain, tumor/muscle, and tumor/blood uptake ratios. Overall, these results suggest that [ 18 F]11b is promising as a tumor imaging agent for positron emission tomography. (author)

3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation.

Science.gov (United States)

Sethi, Pallavi; Jyoti, Amar; Swindell, Elden P; Chan, Ryan; Langner, Ulrich W; Feddock, Jonathan M; Nagarajan, Radhakrishnan; O'Halloran, Thomas V; Upreti, Meenakshi

2015-11-01

An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies. Existing in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Concentrations of formaldehyde in rain waters harvested at the ...

African Journals Online (AJOL)

Formaldehyde has been recognized as one of the most important pollutants and a carcinogen that is present in the air, water, foods, soils, fabrics, cosmetics, cigarette smoke and treated wood. Related health effects and hazards are linked to formaldehyde, depending on mode of exposure which includes: weakness, ...

Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil

Directory of Open Access Journals (Sweden)

Zora Djuric

2017-08-01

Full Text Available Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate. The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1].

Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization

International Nuclear Information System (INIS)

Jang, Ji-Young; Lee, Jong-Kuen; Jeon, Yoon-Kyung; Kim, Chul-Woo

2013-01-01

Tumor-associated macrophages (TAM) play an important role in tumor microenvironment. Particularly, M2 macrophages contribute to tumor progression, depending on the expression of NF-κB. Tumor-derived exosomes can modulate tumor microenvironment by transferring miRNAs to immune cells. Epigallocatechin gallate (EGCG) has well known anti-tumor effects; however, no data are available on the influence of EGCG on communication with cancer cells and TAM. Murine breast cancer cell lines, 4T1, was used for in vivo and ex vivo studies. Exosome was extracted from EGCG-treated 4T1 cells, and the change of miRNAs was screened using microarray. Tumor cells or TAM isolated from murine tumor graft were incubated with exosomes derived from EGCG-treated and/or miR-16 inhibitor-transfected 4T1 cells. Chemokines for monocytes (CSF-1 and CCL-2), cytokines both with high (IL-6 and TGF-β) and low (TNF-α) expression in M2 macrophages, and molecules in NF-κB pathway (IKKα and Iκ-B) were evaluated by RT-qPCR or western blot. EGCG suppressed tumor growth in murine breast cancer model, which was associated with decreased TAM and M2 macrophage infiltration. Expression of chemokine for monocytes (CSF-1 and CCL-2) were low in tumor cells from EGCG-treated mice, and cytokines of TAM was skewed from M2- into M1-like phenotype by EGCG as evidenced by decreased IL-6 and TGF-β and increased TNF-α. Ex vivo incubation of isolated tumor cells with EGCG inhibited the CSF-1 and CCL-2 expression. Ex vivo incubation of TAM with exosomes from EGCG-treated 4T1 cells led to IKKα suppression and concomitant I-κB accumulation; increase of IL-6 and TGF-β; and, decrease of TNF-α. EGCG up-regulated miR-16 in 4T1 cells and in the exosomes. Treatment of tumor cells or TAM with exosomes derived from EGCG-treated and miR-16-knock-downed 4T1 cells restored the above effects on chemokines, cytokines, and NF-κB pathway elicited by EGCG-treated exosomes. Our data demonstrate that EGCG up-regulates miR-16 in

Conditionally reprogrammed cells (CRC) methodology does not allow the in vitro expansion of patient-derived primary and metastatic lung cancer cells.

Science.gov (United States)

Sette, Giovanni; Salvati, Valentina; Giordani, Ilenia; Pilozzi, Emanuela; Quacquarini, Denise; Duranti, Enrico; De Nicola, Francesca; Pallocca, Matteo; Fanciulli, Maurizio; Falchi, Mario; Pallini, Roberto; De Maria, Ruggero; Eramo, Adriana

2018-07-01

Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for non-small cell lung cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC cultures were obtained from both tumor and non-malignant tissues with extraordinary high efficiency. Tumor cells were tracked in vitro through tumorigenicity assay, monitoring of tumor-specific genetic alterations and marker expression. Cultures were composed of EpCAM+ lung epithelial cells lacking tumorigenic potential. NSCLC biopsies-derived cultures rapidly lost patient-specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC cultures examined displayed epithelial lung stem cell phenotype and function. In contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures. In conclusion, patient-derived primary and metastatic lung cancer cells were negatively selected under CRC conditions, limiting the expansion to non-malignant lung epithelial stem cells from either tumor or non-tumor tissue sources. Thus, CRC approach cannot be applied for direct therapeutic testing of patient lung tumor cells, as the tumor-derived CRC cultures are composed of (non-tumoral) airway basal cells. © 2018 UICC.

Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

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Maciej H Swat

Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

MALDI imaging mass spectrometry profiling of N-glycans in formalin-fixed paraffin embedded clinical tissue blocks and tissue microarrays.

Science.gov (United States)

Powers, Thomas W; Neely, Benjamin A; Shao, Yuan; Tang, Huiyuan; Troyer, Dean A; Mehta, Anand S; Haab, Brian B; Drake, Richard R

2014-01-01

A recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) method to spatially profile the location and distribution of multiple N-linked glycan species in frozen tissues has been extended and improved for the direct analysis of glycans in clinically derived formalin-fixed paraffin-embedded (FFPE) tissues. Formalin-fixed tissues from normal mouse kidney, human pancreatic and prostate cancers, and a human hepatocellular carcinoma tissue microarray were processed by antigen retrieval followed by on-tissue digestion with peptide N-glycosidase F. The released N-glycans were detected by MALDI-IMS analysis, and the structural composition of a subset of glycans could be verified directly by on-tissue collision-induced fragmentation. Other structural assignments were confirmed by off-tissue permethylation analysis combined with multiple database comparisons. Imaging of mouse kidney tissue sections demonstrates specific tissue distributions of major cellular N-linked glycoforms in the cortex and medulla. Differential tissue distribution of N-linked glycoforms was also observed in the other tissue types. The efficacy of using MALDI-IMS glycan profiling to distinguish tumor from non-tumor tissues in a tumor microarray format is also demonstrated. This MALDI-IMS workflow has the potential to be applied to any FFPE tissue block or tissue microarray to enable higher throughput analysis of the global changes in N-glycosylation associated with cancers.

Soft tissue masses with myxoid stroma: Can conventional magnetic resonance imaging differentiate benign from malignant tumors?

Energy Technology Data Exchange (ETDEWEB)

Crombe, A., E-mail: amandine.crombe@ens-lyon.fr [Department of Radiology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Alberti, N. [Department of Radiology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Stoeckle, E. [Department of Surgery, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Brouste, V. [Clinical and Epidemiological Research Unit, Institut Bergonié, 33000 Bordeaux (France); Buy, X. [Department of Radiology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Coindre, J-M. [Department of Pathology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Kind, M. [Department of Radiology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France)

2016-10-15

Objectives: To retrospectively evaluate the diagnostic performance of morphological signs observed on conventional magnetic resonance (MR) imaging to differentiate benign from malignant peripheral solid tumors of soft tissue with myxoid stroma. Methods: MR images from 95 consecutive histopathologically proven tumors (26 benign and 69 malignant) of soft tissues with myxoid components were evaluated in our tertiary referral center. Two radiologists, blind to pathology results, independently reviewed conventional MR sequences including at least a) one T2-weighted sequence with or without fat suppression; b) one T1-weighted sequence without fat suppression; and c) one T1-weighted sequence with gadolinium-complex contrast enhancement and fat suppression. Multiple criteria were defined to analyze morphology, margins, architecture and tumor periphery and evaluated for each lesion. Intra- and inter-observer reproducibility and Odds ratios were calculated for each criterion. Results: The most relevant and reproducible criteria to significantly predict malignancy were: (1) ill-defined tumor margins, (2) a hemorrhagic component, (3) intra-tumoral fat, (4) fibrosis and (5) the “tail sign”. A lesion is classified as malignant if any of these 5 criteria is present, and benign if none of them are observed. Therefore, this combination provides a sensitivity of 92.9% and a specificity of 93.3%. Conclusion: Conventional MR imaging provides reproducible criteria that can be combined to differentiate between benign and malignant solid tumors of soft tissue with myxoid stroma.

PASSIVE CAVITATION DETECTION DURING PULSED HIFU EXPOSURES OF EX VIVO TISSUES AND IN VIVO MOUSE PANCREATIC TUMORS

Science.gov (United States)

Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

2014-01-01

Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rarefactional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms, pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KPC mice and closely recapitulate human disease in their morphology. The cavitation threshold, defined at 50 % cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but ex vivo it decreased rapidly and stopped over the first few pulses

Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.

Science.gov (United States)

Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

2014-07-01

Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped

The Potential Biomarkers and Immunological Effects of Tumor-Derived Exosomes in Lung Cancer

Directory of Open Access Journals (Sweden)

Shamila D. Alipoor

2018-04-01

Full Text Available Lung cancer remains the leading cause of cancer-related deaths worldwide. Despite considerable achievements in lung cancer diagnosis and treatment, the global control of the disease remains problematic. In this respect, greater understanding of the disease pathology is crucially needed for earlier diagnosis and more successful treatment to be achieved. Exosomes are nano-sized particles secreted from most cells, which allow cross talk between cells and their surrounding environment via transferring their cargo. Tumor cells, just like normal cells, also secrete exosomes that are termed Tumor-Derived Exosome or tumor-derived exosome (TEX. TEXs have gained attention for their immuno-modulatory activities, which strongly affect the tumor microenvironment and antitumor immune responses. The immunological activity of TEX influences both the innate and adaptive immune systems including natural killer cell activity and regulatory T-cell maturation as well as numerous anti-inflammatory responses. In the context of lung cancer, TEXs have been studied in order to better understand the mechanisms underlying tumor metastasis and progression. As such, TEX has the potential to act both as a biomarker for lung cancer diagnosis as well as the response to therapy.

Tumor-derived exosomes in cancer progression and treatment failure

Science.gov (United States)

Shen, Bo; Feng, Jifeng

2015-01-01

Exosomes have diameter within the range of 30-100nm and spherical to cup-shaped nanoparticles with specific surface molecular characteristics, such as CD9 and CD63. These vesicles are present in nearly all human body fluids, including blood plasma/serum, saliva, breast milk, cerebrospinal fluid, urine, semen, and particularly enriched in tumor microenvironment. Exosomes contain multiple proteins, DNA, mRNA, miRNA, long non-coding RNA, and even genetic materials of viruses/prions. These materials are biochemically and functionally distinct and can be transferred to a recipient cell where they regulate protein expression and signaling pathways. Recently, exosomes are demonstrated to have a close relationship with tumor development and metastasis. Exosomes influence therapeutic effect in cancer patients. In this review, we describe the biogenesis, composition, and function of exosomes. The mechanism on how tumor-derived exosomes contribute to cancer progression and clinical treatment failure is also described, with special focus on their potential applications in cancer therapy. PMID:26452221

Tumor-derived exosomes in cancer progression and treatment failure.

Science.gov (United States)

Yu, Shaorong; Cao, Haixia; Shen, Bo; Feng, Jifeng

2015-11-10

Exosomes have diameter within the range of 30-100 nm and spherical to cup-shaped nanoparticles with specific surface molecular characteristics, such as CD9 and CD63. These vesicles are present in nearly all human body fluids, including blood plasma/serum, saliva, breast milk, cerebrospinal fluid, urine, semen, and particularly enriched in tumor microenvironment. Exosomes contain multiple proteins, DNA, mRNA, miRNA, long non-coding RNA, and even genetic materials of viruses/prions. These materials are biochemically and functionally distinct and can be transferred to a recipient cell where they regulate protein expression and signaling pathways. Recently, exosomes are demonstrated to have a close relationship with tumor development and metastasis. Exosomes influence therapeutic effect in cancer patients. In this review, we describe the biogenesis, composition, and function of exosomes. The mechanism on how tumor-derived exosomes contribute to cancer progression and clinical treatment failure is also described, with special focus on their potential applications in cancer therapy.

Exploration of two methods for quantitative Mitomycin C measurement in tumor tissue in vitro and in vivo

DEFF Research Database (Denmark)

Fischer, Lee MacKenzie; Vásquez, Juan Luis; Gehl, Julie

2013-01-01

Two methods of quantifying Mitomycin C in tumor tissue are explored. A method of ultraviolet-visible absorption microscopy is developed and applied to measure the concentration of Mitomycin C in preserved mouse tumor tissue, as well as in gelatin samples. Concentrations as low as 60 μM can...... be resolved using this technique in samples that do not strongly scatter light. A novel method for monitoring the Mitomycin C concentrations inside a tumor is developed, based on microdialysis and ultraviolet-visible spectroscopy. A pump is used to perfuse a microdialysis probe with Ringer’s solution, which...

Suitability of the Cellient (TM) cell block method for diagnosing soft tissue and bone tumors

NARCIS (Netherlands)

Song, W.; van Hemel, B. M.; Suurmeijer, A. J. H.

BACKGROUNDThe diagnosis of tumors of soft tissue and bone (STB) heavily relies on histological biopsies, whereas cytology is not widely used. Cellient(TM) cell blocks often contain small tissue fragments. In addition to Hematoxylin and Eosin (H&E) interpretation of histological features,

Tumor tropism of intravenously injected human-induced pluripotent stem cell-derived neural stem cells and their gene therapy application in a metastatic breast cancer model.

Science.gov (United States)

Yang, Jing; Lam, Dang Hoang; Goh, Sally Sallee; Lee, Esther Xingwei; Zhao, Ying; Tay, Felix Chang; Chen, Can; Du, Shouhui; Balasundaram, Ghayathri; Shahbazi, Mohammad; Tham, Chee Kian; Ng, Wai Hoe; Toh, Han Chong; Wang, Shu

2012-05-01

Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we used a conventional lentiviral transduction method to derive human-induced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole-body imaging technology, we demonstrated that after tail vein injection, these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor-bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumor-bearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help to overcome problems associated with allogeneic transplantation of other types of human NSCs. Copyright © 2012 AlphaMed Press.

Histological and molecular evaluation of patient-derived colorectal cancer explants.

Directory of Open Access Journals (Sweden)

Joshua M Uronis

Full Text Available Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

PASSIVE CAVITATION DETECTION DURING PULSED HIFU EXPOSURES OF EX VIVO TISSUES AND IN VIVO MOUSE PANCREATIC TUMORS

OpenAIRE

Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

2014-01-01

Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitatio...

A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

Directory of Open Access Journals (Sweden)

Han Jin Cho

2015-04-01

Full Text Available To examine the effects of high-fat diet (HFD containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

Genotoxicity of formaldehyde: Molecular basis of DNA damage and mutation

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Masanobu eKawanishi

2014-09-01

Full Text Available Formaldehyde is commonly used in the chemical industry and is present in the environment, such as vehicle emissions, some building materials, food and tobacco smoke. It also occurs as a natural product in most organisms, the sources of which include a number of metabolic processes. It causes various acute and chronic adverse effects in humans if they inhale its fumes. Among the chronic effects on human health, we summarize data on genotoxicity and carcinogenicity in this review, and we particularly focus on the molecular mechanisms involved in the formaldehyde mutagenesis. Formaldehyde mainly induces N-hydroxymethyl mono-adducts on guanine, adenine and cytosine, and N-methylene crosslinks between adjacent purines in DNA. These crosslinks are types of DNA damage potentially fatal for cell survival if they are not removed by the nucleotide excision repair pathway. In the previous studies, we showed evidence that formaldehyde causes intra-strand crosslinks between purines in DNA using a unique method (Matsuda et al. Nucleic Acids Res. 26, 1769-1774,1998. Using shuttle vector plasmids, we also showed that formaldehyde as well as acetaldehyde induces tandem base substitutions, mainly at 5’-GG and 5’-GA sequences, which would arise from the intra-strand crosslinks. These mutation features are different from those of other aldehydes such as crotonaldehyde, acrolein, glyoxal and methylglyoxal. These findings provide molecular clues to improve our understanding of the genotoxicity and carcinogenicity of formaldehyde.

ISOFORMAL: isotopic tracing of formaldehyde sources in housing. Intermediary report

International Nuclear Information System (INIS)

2011-01-01

The authors report an investigation which comprised a sampling and a chemical and isotopic analysis of emissions from the main indoor formaldehyde pollution sources in order to create a exhaustive database. Emissions which are characteristic of motorcar traffic, are also sampled in order to asses their possible contribution in the housing air. This step will be used to develop emission simulations of formaldehyde sources in a laboratory-house in order to validate the isotopic approach as tracing tool for sources of this compound. The report describes the carbon and hydrogen steady isotopes. It presents the sampling procedure, reports the determination of formaldehyde concentrations by high performance liquid chromatography with UV detectors, the use of gas source mass spectrometry, and the analytic development of the isotopic analysis of formaldehyde by gas chromatography combustion isotope ratio mass spectrometry. Outdoor and indoor pollution sources are discussed

Investigation of the detoxification mechanism of formaldehyde-treated tetanus toxin

DEFF Research Database (Denmark)

Thaysen-Andersen, Morten; Jørgensen, Sys Borcher; Wilhelmsen, Ellen Sloth

2007-01-01

and properties of the vaccine component, occurs through partly unknown chemical modifications of the toxin. The aim of this study was to gain knowledge of the detoxification mechanism in the generation of the tetanus vaccine. Two approaches were chosen: (i) the effect of changes in the concentrations of lysine...... The tetanus vaccine is based on the extremely potent tetanus neurotoxin (TeNT), which is converted by treatment with formaldehyde and lysine into the non-toxic, but still immunogenic tetanus toxoid (TTd). This formaldehyde-induced detoxification, which to a large extend determines the quality...... and formaldehyde in the detoxification process and (ii) characterisation of the chemically detoxified TTd. (i) We examined a number of TTd components that was produced by varying the concentrations of formaldehyde and lysine during the inactivation. Toxicity tests showed that the detoxification failed when...

Mechanism of endothelial progenitor cell recruitment into neo-vessels in adjacent non-tumor tissues in hepatocellular carcinoma

International Nuclear Information System (INIS)

Yu, De-cai; Chen, Jun; Sun, Xi-tai; Zhuang, Lin-yuan; Jiang, Chun-ping; Ding, Yi-tao

2010-01-01

We investigated the distribution and clinical significance of mobilized endothelial progenitor cells (EPCs) in hepatocellular carcinoma (HCC). We found that many more EPCs were recruited to nonmalignant liver tissue (especially into adjacent non-tumor tissues (AT)) than to tumor vessels. These results suggest that the mechanism underlying the recruitment of EPCs into microvessels in AT merits further investigation Angiogenic factors were detected in three tissue microarrays comprising normal liver, paired tumor tissue (TT) and AT from 105 patients (who had undergone hepatectomy for HCC) using immunohistochemistry. Also, the number of EPCs (positive for Sca-1, Flk-1 and c-Kit) in the blood and liver of cirrhotic mice were determined by flow cytometry and immunohistochemistry. The distribution of these labeled EPCs in tumor and non-tumor tissues was then studied. The results from the tissue microarrays showed that the expression levels of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, and endostatin were significantly higher in AT than in either normal liver or TT (p < 0.05), but no significant difference was found in the expression levels of COX-2 and NOS-2 between AT and TT. The expression of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, endostatin, COX-2, and NOS-2 in normal liver tissue was weaker than that in AT or TT. In cirrhotic mice, the number of circulating endothelial progenitor cells gradually increased, before decreasing again. In this mouse model, increased numbers of EPCs were recruited and homed specifically to the cirrhotic liver. Both liver cirrhosis and HCC led to increased expression of pro-angiogenic factors, which resulted in the recruitment of EPCs into AT. Also, EPCs were mobilized, recruited and homed to cirrhotic liver. The unique pathology of HCC coupled with liver cirrhosis may, therefore, be associated with the distribution and function of EPCs

Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.

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Woo, Hae-Mi; Kang, Ji-Hye; Kawada, Teruo; Yoo, Hoon; Sung, Mi-Kyung; Yu, Rina

2007-02-13

Inflammation plays a key role in obesity-related pathologies such as cardiovascular disease, type II diabetes, and several types of cancer. Obesity-induced inflammation entails the enhancement of the recruitment of macrophages into adipose tissue and the release of various proinflammatory proteins from fat tissue. Therefore, the modulation of inflammatory responses in obesity may be useful for preventing or ameliorating obesity-related pathologies. Some spice-derived components, which are naturally occurring phytochemicals, elicit antiobesity and antiinflammatory properties. In this study, we investigated whether active spice-derived components can be applied to the suppression of obesity-induced inflammatory responses. Mesenteric adipose tissue was isolated from obese mice fed a high-fat diet and cultured to prepare an adipose tissue-conditioned medium. Raw 264.7 macrophages were treated with the adipose tissue-conditioned medium with or without active spice-derived components (i.e., diallyl disulfide, allyl isothiocyanate, piperine, zingerone and curcumin). Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha), nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The active spice-derived components markedly suppressed the migration of macrophages induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent manner. Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes

Computer modeling of the combined effects of perfusion, electrical conductivity, and thermal conductivity on tissue heating patterns in radiofrequency tumor ablation.

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Ahmed, Muneeb; Liu, Zhengjun; Humphries, Stanley; Goldberg, S Nahum

2008-11-01

To use an established computer simulation model of radiofrequency (RF) ablation to characterize the combined effects of varying perfusion, and electrical and thermal conductivity on RF heating. Two-compartment computer simulation of RF heating using 2-D and 3-D finite element analysis (ETherm) was performed in three phases (n = 88 matrices, 144 data points each). In each phase, RF application was systematically modeled on a clinically relevant template of application parameters (i.e., varying tumor and surrounding tissue perfusion: 0-5 kg/m(3)-s) for internally cooled 3 cm single and 2.5 cm cluster electrodes for tumor diameters ranging from 2-5 cm, and RF application times (6-20 min). In the first phase, outer thermal conductivity was changed to reflect three common clinical scenarios: soft tissue, fat, and ascites (0.5, 0.23, and 0.7 W/m- degrees C, respectively). In the second phase, electrical conductivity was changed to reflect different tumor electrical conductivities (0.5 and 4.0 S/m, representing soft tissue and adjuvant saline injection, respectively) and background electrical conductivity representing soft tissue, lung, and kidney (0.5, 0.1, and 3.3 S/m, respectively). In the third phase, the best and worst combinations of electrical and thermal conductivity characteristics were modeled in combination. Tissue heating patterns and the time required to heat the entire tumor +/-a 5 mm margin to >50 degrees C were assessed. Increasing background tissue thermal conductivity increases the time required to achieve a 50 degrees C isotherm for all tumor sizes and electrode types, but enabled ablation of a given tumor size at higher tissue perfusions. An inner thermal conductivity equivalent to soft tissue (0.5 W/m- degrees C) surrounded by fat (0.23 W/m- degrees C) permitted the greatest degree of tumor heating in the shortest time, while soft tissue surrounded by ascites (0.7 W/m- degrees C) took longer to achieve the 50 degrees C isotherm, and complete ablation

Elevated pressure improves the extraction and identification of proteins recovered from formalin-fixed, paraffin-embedded tissue surrogates.

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Carol B Fowler

2010-12-01

Full Text Available Proteomic studies of formalin-fixed paraffin-embedded (FFPE tissues are frustrated by the inability to extract proteins from archival tissue in a form suitable for analysis by 2-D gel electrophoresis or mass spectrometry. This inability arises from the difficulty of reversing formaldehyde-induced protein adducts and cross-links within FFPE tissues. We previously reported the use of elevated hydrostatic pressure as a method for efficient protein recovery from a hen egg-white lysozyme tissue surrogate, a model system developed to study formalin fixation and histochemical processing.In this study, we demonstrate the utility of elevated hydrostatic pressure as a method for efficient protein recovery from FFPE mouse liver tissue and a complex multi-protein FFPE tissue surrogate comprised of hen egg-white lysozyme, bovine carbonic anhydrase, bovine ribonuclease A, bovine serum albumin, and equine myoglobin (55∶15∶15∶10∶5 wt%. Mass spectrometry of the FFPE tissue surrogates retrieved under elevated pressure showed that both the low and high-abundance proteins were identified with sequence coverage comparable to that of the surrogate mixture prior to formaldehyde treatment. In contrast, non-pressure-extracted tissue surrogate samples yielded few positive and many false peptide identifications. Studies with soluble formalin-treated bovine ribonuclease A demonstrated that pressure modestly inhibited the rate of reversal (hydrolysis of formaldehyde-induced protein cross-links. Dynamic light scattering studies suggest that elevated hydrostatic pressure and heat facilitate the recovery of proteins free of formaldehyde adducts and cross-links by promoting protein unfolding and hydration with a concomitant reduction in the average size of the protein aggregates.These studies demonstrate that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues in a form suitable for proteomic analysis.

Elevated Pressure Improves the Extraction and Identification of Proteins Recovered from Formalin-Fixed, Paraffin-Embedded Tissue Surrogates

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Fowler, Carol B.; Chesnick, Ingrid E.; Moore, Cedric D.; O'Leary, Timothy J.; Mason, Jeffrey T.

2010-01-01

Background Proteomic studies of formalin-fixed paraffin-embedded (FFPE) tissues are frustrated by the inability to extract proteins from archival tissue in a form suitable for analysis by 2-D gel electrophoresis or mass spectrometry. This inability arises from the difficulty of reversing formaldehyde-induced protein adducts and cross-links within FFPE tissues. We previously reported the use of elevated hydrostatic pressure as a method for efficient protein recovery from a hen egg-white lysozyme tissue surrogate, a model system developed to study formalin fixation and histochemical processing. Principal Findings In this study, we demonstrate the utility of elevated hydrostatic pressure as a method for efficient protein recovery from FFPE mouse liver tissue and a complex multi-protein FFPE tissue surrogate comprised of hen egg-white lysozyme, bovine carbonic anhydrase, bovine ribonuclease A, bovine serum albumin, and equine myoglobin (55∶15∶15∶10∶5 wt%). Mass spectrometry of the FFPE tissue surrogates retrieved under elevated pressure showed that both the low and high-abundance proteins were identified with sequence coverage comparable to that of the surrogate mixture prior to formaldehyde treatment. In contrast, non-pressure-extracted tissue surrogate samples yielded few positive and many false peptide identifications. Studies with soluble formalin-treated bovine ribonuclease A demonstrated that pressure modestly inhibited the rate of reversal (hydrolysis) of formaldehyde-induced protein cross-links. Dynamic light scattering studies suggest that elevated hydrostatic pressure and heat facilitate the recovery of proteins free of formaldehyde adducts and cross-links by promoting protein unfolding and hydration with a concomitant reduction in the average size of the protein aggregates. Conclusions These studies demonstrate that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues in a form

Tumor sterilization dose and radiation induced change of the brain tissue in radiotherapy of brain tumors

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Yoshii, Yoshihiko; Maki, Yutaka; Takano, Shingo

1987-01-01

Ninety-seven patients with brain tumors (38 gliomas, 26 brain metastases, 18 sellar tumors, 15 others) were treated by cobalt gamma ray or proton radiotherapy. In this study, normal brain injury due to radiation was analysed in terms of time-dose-fractionation (TDF), nominal standard dose (NSD) by the Ellis formula and NeuNSD by a modification in which the N exponent was -0.44 and the T exponent was -0.06. Their calculated doses were analysed in relationship to the normal brain radiation induced change (RIC) and the tumor sterilization dose. All brain tumors with an exception of many patients with brain metastases were received a surgical extirpation subtotally or partially prior to radiotherapy. And all patients with glioma and brain metastasis received also immuno-chemotherapy in the usual manner during radiotherapy. The calculated dose expressed by NeuNSD and TDF showed a significant relationship between a therapeutic dose and a postradiation time in terms of the appearance of RIC. It was suggested that RIC was caused by a dose over 800 in NeuNSD and a dose over 70 in TDF. Furthermore, it was suggested that an aged patient and a patient who had the vulnerable brain tissue to radiation exposure in the irradiated field had the high risk of RIC. On the other hand, our results suggested that the tumor sterilization dose should be over 1,536 NeuNSD and the irradiated method should be further considered in addition to the radiobiological concepts for various brain tumors. (author)