Albumin-bound paclitaxel in solid tumors: clinical development and future directions.

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Kundranda, Madappa N; Niu, Jiaxin

2015-01-01

Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel's indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.

Solid and cystic pseudopapillary tumor of the pancreas: A case report

Directory of Open Access Journals (Sweden)

Milošević Bojan Z.

2013-01-01

Full Text Available Introduction. Solid and cystic pseudopapillary tumor of the pancreas is a rare tumor of the pancreas, for the first time described by Frantz et al. in 1959. The majority of patients are young females and most of them are asymptomatic. Case Outline. We report a case of 25-year old woman who was admitted to our institution with abdominal pain and a palpable mass in the left hypochondrial area. US and CT scan revealed a solid and cystic pseudopapillary tumor in the head of the pancreas. The patient was treated by Whipple procedure, modification Longmire-Traverso. There was no metastatic disease either in the liver or peritoneum. Histologically the tumor was diagnosed as a solid and cystic pseudopapillary tumor of the pancreas. Conclusion. The unclear pre-operative diagnoses, together with incidence of potential malignancy as well as good outcome with resection, suggest that all suspected cystic tumors of the pancreas should be resected. The exact diagnosis is based on histological findings. [Projekat Ministarstva nauke Republike Srbije, br. III41007 i br. III41010

CAR-T cells: the long and winding road to solid tumors.

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D'Aloia, Maria Michela; Zizzari, Ilaria Grazia; Sacchetti, Benedetto; Pierelli, Luca; Alimandi, Maurizio

2018-02-15

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles.

Bacteria-mediated in vivo delivery of quantum dots into solid tumor

Energy Technology Data Exchange (ETDEWEB)

Liu, Ying [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Zhou, Mei [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Luo, Dan; Wang, Lijun; Hong, Yuankai [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Yang, Yepeng, E-mail: yangyepeng@bjmu.edu.cn [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Sha, Yinlin, E-mail: shyl@hsc.pku.edu.cn [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Biomed-X Center, Peking University, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China)

2012-09-07

Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

Obtaining S values for rectangular--solid tumors inside rectangular--solid host organs

International Nuclear Information System (INIS)

Stinchcomb, T.G.; Durham, J.S.; Fisher, D.R.

1991-01-01

A method is described for obtaining S values between a tumor and its host organ for use with the MIRD formalism. It applies the point-source specific absorbed fractions for an infinite water medium, tabulated by Berger, to a rectangular solid of arbitrary dimensions which contains a rectangular tumor of arbitrary dimensions. Contributions from pairs of source and target volume elements are summed for the S values between the tumor and itself, between the remaining healthy host organ and itself, and between the tumor and the remaining healthy host organ, with the reciprocity theorem assumed for the last. This method labeled MTUMOR, is interfaced with the widely used MIRDOSE program which incorporates the MIRD formalism. An example is calculated

Combination effect of cisplatin and radiation in murine solid tumors

International Nuclear Information System (INIS)

Egawa, Shin; Lee, Kan-ei; Ishibashi, Akira; Komiyama, Hiroki; Umezawa, Iwao.

1986-01-01

The combination effect of cisplatin and radiation was studied using the two different murine systems of sarcoma 180 and Ehrlich solid tumors. In sarcoma 180 solid tumor the minimal effective doses (MED) of cisplatin and radiation were 19.5 mg/kg and 10375 rad respectively whereas these doses did not show any effective antitumor activity practically. Administration of cisplatin with a doses of 9 mg/kg given 24 hours before radiation (1000 rad), however, showed synergistic antitumor activity. In Ehrlich solid tumor the MED of cisplatin and radiation were 13.8 mg/kg and 2892 rad respectively. Treatment with cisplatin, 3, 6 or 9 mg/kg, given 24 hours before radiation (1000 rad) showed also synergistic antitumor activity also. Sodium thiosulfate (STS) rescue was effective in reducing toxicity of cisplatin on combined use of the drug with radiation. Cell kinetics of sarcoma 180 solid tumor in vivo after the combined treatment was analyzed by computer aided flowcytometry. Accumulation of cells in the radiosensitive G 2 + M phase was observed 18 to 42 hours after a single intraperitoneal administration of 9 mg/kg of cisplatin. It is strongly suggested that this synchronization is one of the mechanisms of the synergism in the combination therapy. (author)

Electron transfer reactions in microporous solids

Energy Technology Data Exchange (ETDEWEB)

Mallouk, T.E.

1993-01-01

Basic thrust the research program involves use of microporous solids (zeolites, clays, layered and tunnel structure oxide semiconductors) as organizing media for artificial photosynthetic systems. Purpose of the microporous solid is twofold. First, it induces spatial organization of photoactive and electroactive components (sensitizers, semiconductor particles, electron relays, and catalysts) at the solid-solution interface, enhancing the quantum efficiency of charge separation and separating physically the ultimate electron donor and acceptor in the electron transport chain. Second, since the microcrystalline solid admits only molecules of a certain charge and size, it is possible to achieve permanent charge separation by sieving chemical photoproducts (e.g., H[sub 2] and I[sub 3][sup [minus

Radio-immunotherapy of solid tumors

International Nuclear Information System (INIS)

Chatal, J.F.; Faivre Chauvet, A.; Bardies, M.; Kraeber-Bodere, F.; Barbet, J.

2001-01-01

A convincing efficacy of radio-immunotherapy of solid tumors has not been documented yet in clinical studies. Consequently, a methodological optimization is needed within the scope in increasing absorbed doses delivered to tumor targets by amplifying cumulative tumor activity and in the same time in reducing absorbed doses delivered normal organs. Multi-step pre-targeting techniques allow to approach these goals. The most developed technique is based on the high affinity for biotin. In a first step an anti-tumor antibody coupled to avidin or biodin is injected. In a second step, 24 hours later, the circulating residual immuno-conjugate is bound to a molecular complex and eliminated through the reticulo endothelial system of the liver ('chase'phase). A third step, a few hours later, consists in injecting biotin coupled to DOTA chelating agent and labeled with yttrium 90. This small molecule rapidly diffuses to tumor targets and binds to pre-localized immuno-conjugate. Another technique, designed and developed in France, is based on antigen-antibody affinity. In a first step an anti-tumor / anti-hapten bi-specific antibody is injected and, in a second step, a few days later, the small hapten molecule is radiolabeled with I-131 and injected. It diffuses rapidly to the tumor targets and binds to the anti-hapten arm of the pre-localized bi-specific antibody. An alternative way to increase radio-immunotherapy efficacy consists in combining this low-dose rate irradiation to radiosensitizing molecules within the scope of an additive or supra additive effect which has previously documented. (author)

Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors.

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Ham, Stephanie L; Joshi, Ramila; Luker, Gary D; Tavana, Hossein

2016-11-01

Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self-renewal and tumor-initiation capabilities. Both hypoxia and CSCs are associated with resistance to therapies and tumor relapse. This study demonstrates that 3D cancer cell models, known as tumor spheroids, generated with a polymeric aqueous two-phase system (ATPS) technology capture these important biological processes. Similar to solid tumors, spheroids of triple negative breast cancer cells deposit major extracellular matrix proteins. The molecular analysis establishes presence of hypoxic cells in the core region and expression of CSC gene and protein markers including CD24, CD133, and Nanog. Importantly, these spheroids resist treatment with chemotherapy drugs. A combination treatment approach using a hypoxia-activated prodrug, TH-302, and a chemotherapy drug, doxorubicin, successfully targets drug resistant spheroids. This study demonstrates that ATPS spheroids recapitulate important biological and functional properties of solid tumors and provide a unique model for studies in cancer research. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Endoscopic ultrasound-guided radiofrequency ablation for management of benign solid pancreatic tumors.

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Choi, Jun-Ho; Seo, Dong-Wan; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

2018-05-04

 Radiofrequency ablation (RFA) has been increasingly employed in experimental and clinical settings for the management of pancreatic lesions. This study aimed to assess the safety and efficacy of endoscopic ultrasound (EUS)-guided RFA for benign solid pancreatic tumors.  In a single-center, prospective study, 10 patients with benign solid pancreatic tumors underwent EUS-RFA. After the RFA electrode had been inserted into the pancreatic mass, the radiofrequency generator was activated to deliver 50 W of ablation power.  Among the 10 patients, 16 sessions of EUS-RFA were successfully performed. Diagnoses included nonfunctioning neuroendocrine tumor (n = 7), solid pseudopapillary neoplasm (n = 2), and insulinoma (n = 1); the median largest diameter of the tumors was 20 mm (range 8 - 28 mm). During follow-up (median 13 months), radiologic complete response was achieved in seven patients. Two adverse events (12.4 %; 1 moderate and 1 mild) occurred.  EUS-RFA may be a safe and potentially effective treatment option in selected patients with benign solid pancreatic tumors. Multiple sessions may be required if there is a remnant tumor, and adverse events must be carefully monitored. © Georg Thieme Verlag KG Stuttgart · New York.

Chimeric antigen receptor T-cell therapy for solid tumors

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Kheng Newick

2016-01-01

Full Text Available Chimeric antigen receptor (CAR T cells are engineered constructs composed of synthetic receptors that direct T cells to surface antigens for subsequent elimination. Many CAR constructs are also manufactured with elements that augment T-cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematological malignancies (e.g., CD19 CARs in leukemias. This success is not yet extrapolated to solid tumors, and the reasons for this are being actively investigated. Here in this mini-review, we discuss some of the key hurdles encountered by CAR T cells in the solid tumor microenvironment.

Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

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Zhang, Bing-Lan; Qin, Di-Yuan; Mo, Ze-Ming; Li, Yi; Wei, Wei; Wang, Yong-Sheng; Wang, Wei; Wei, Yu-Quan

2016-04-01

Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

Potential of epigenetic therapies in the management of solid tumors

International Nuclear Information System (INIS)

Valdespino, Victor; Valdespino, Patricia M

2015-01-01

Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails

Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.

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Taniguchi, Shun'ichiro; Fujimori, Minoru; Sasaki, Takayuki; Tsutsui, Hiroko; Shimatani, Yuko; Seki, Keiichi; Amano, Jun

2010-09-01

Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. © 2010 Japanese Cancer Association.

In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.

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Boissonnas, Alexandre; Fetler, Luc; Zeelenberg, Ingrid S; Hugues, Stéphanie; Amigorena, Sebastian

2007-02-19

Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8(+) cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration.

Turnover rate of hypoxic cells in solid tumors

International Nuclear Information System (INIS)

Ljungkvist, A.S.E.; Bussink, J.; Rijken, P.F.J.W.; Van Der Kogel, A.J.

2003-01-01

Most solid tumors contain hypoxic cells, and both the amount and duration of tumor hypoxia has been shown to influence the effect of radiation treatment negatively. It is important to understand the dynamic processes within the hypoxic cell population in non-treated tumors, and the effect of different treatment modalities on the kinetics of hypoxic cells to be able to design optimal combined modality treatments. The turnover rate of hypoxic cells was analyzed in three different solid tumor models with a double bio-reductive hypoxic marker assay with sequential injection of the two hypoxic markers. Previously it was shown that this assay could be used to detect both a decrease and an increase of tumor hypoxia in relation to the tumor vasculature with high spatial resolution. In this study the first hypoxic marker, pimonidazole, was administered at variable times relative to tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. The hypoxic cell turnover rate was calculated as the loss of pimonidazole positive cells relative to CCI-103F. The murine C38 line had the fastest hypoxic turnover rate of 60% /24h and the human xenograft line SCCNij3 had the slowest hypoxic turnover rate of 30% /24 h. The hypoxic turnover rate was most heterogeneous in the SCCNij3 line that even contained viable groups of cells that had been hypoxic for at least 5 days. The human xenograft line MEC82 fell in between with a hypoxic turnover rate of 50% /24 h. The hypoxic cell turnover was related to the potential tumor volume doubling time (Tpot) with a Tpot of 26h in C38 and 103h in SCCNij3. The dynamics of hypoxic cells, quantified with a double hypoxic marker method, showed large differences in hypoxic cell turnover rate and were related to Tpot

Disseminated intravascular coagulation in solid tumors

International Nuclear Information System (INIS)

Terzieff, V.; Alonso, I.; Vázquez, A.

2004-01-01

It is estimated that 20-25% of cases of disseminated intravascular coagulation (DIC) relate to an underlying neoplasia primarily hematologic. It is estimated that about 5% of patients with solid tumors have CID clinic, although the incidence of subclinical alterations is much higher. The CID is not limited to the activation of the coagulation cascade, which leads to bleeding micro thrombosis and consumption of coagulation factors. Solid tumors are frequently associated adenocarcinomas producers mucin (especially gastric), usually in the context of a disseminated disease. The mucin may act as a promoter of the cascade, but probably it is a multi-event. High levels of TNF to produced by the tumor mass and chemotherapy-induced cell lysis have Also linked. Although the bleeding is usually oriented diagnosis, the most frequent cause of death is thrombosis. There are no specific tests for diagnosis. Elevated levels of D-dimer and products oriented fibrinogen degradation diagnosis. No reduction fibrinogen and almost always, one thrombocytopenia consumption. Treatment is complex and there is no consensus on many points. To recover the lost factors for consumption, it is recommended to use fresh frozen plasma and / or washed red blood cells. the heparin anticoagulation low dose is indicated since the disease causal can not be controlled quickly, but should not be initiated if there thrombocytopenia 50.000.El under profuse bleeding can require the use of tranexamic acid or EACA. Acute DIC, the case of our patient, is rare and very serious

Pregnancy following Radical Resection of Solid Pseudopapillary Tumor of the Pancreas

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James M. O’Brien

2014-01-01

Full Text Available Solid pseudopapillary tumor of the pancreas is a rare tumor seen in predominately young women and carries a low malignant potential. We discuss a patient, who presented to our high risk clinic, with a clinical history of solid pseudopapillary tumor of the pancreas, predating her pregnancy. The patient had undergone previous surgery and imaging which had excluded recurrence of disease; however, increased attention was paid to the patient during her pregnancy secondary to elevated hormonal levels of progesterone, which any residual disease would have a heightened sensitivity to. In cases of pregnant patients with a history of pancreatic tumors, a multidisciplinary approach with maternal fetal medicine, medicine, and general surgery is appropriate and can result in a healthy mother and healthy term infant.

Challenges and prospects of chimeric antigen receptor T cell therapy in solid tumors.

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Jindal, Vishal; Arora, Ena; Gupta, Sorab

2018-05-05

Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors. In this article, we will discuss the challenges faced in improving the outcome of CAR T cell therapy in solid tumors and various strategies adopted to curb them.

Radiotherapy of the most frequent solid tumors in childhood

International Nuclear Information System (INIS)

Pfeiffer, J.; Kamprad, F.

1980-01-01

During the past decade the prognosis of malignant tumors in childhood could be clearly improved, realized by combining surgery, radiation therapy and chemotherapy. Recommendations for the use of radiotherapy for the most frequent solid tumors in childhood are represented basing on the experience of the study groups 'Pediatric Hematology and Oncology' of the Society for Pediatrics of the GDR and 'Tumors in Childhood' of the Section of Children's Surgery of the GDR. Besides general problems which have to be taken into consideration in the treatment of infantile tumors the radiotherapeutical measures for Wilms' tumors, neuroblastomas, cerebral tumors, embryonal sarcomas of the soft parts and bone tumors are discussed. The necessary close cooperation of the attending branches is pointed out and both the regional centralization of patients' care and a superregional cooperation are required. (author)

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

Science.gov (United States)

Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

2018-01-01

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

Directory of Open Access Journals (Sweden)

Muhammad Kashif Riaz

2018-01-01

Full Text Available Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications

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Hamid R. Mirzaei

2017-12-01

Full Text Available Adoptive cellular immunotherapy (ACT employing engineered T lymphocytes expressing chimeric antigen receptors (CARs has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

Introduction to solid state electronics

CERN Document Server

Wang, FFY

1989-01-01

This textbook is specifically tailored for undergraduate engineering courses offered in the junior year, providing a thorough understanding of solid state electronics without relying on the prerequisites of quantum mechanics. In contrast to most solid state electronics texts currently available, with their generalized treatments of the same topics, this is the first text to focus exclusively and in meaningful detail on introductory material. The original text has already been in use for 10 years. In this new edition, additional problems have been added at the end of most chapters. These proble

Recent advances of bispecific antibodies in solid tumors

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Shengnan Yu

2017-09-01

Full Text Available Abstract Cancer immunotherapy is the most exciting advancement in cancer therapy. Similar to immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T, bispecific antibody (BsAb is attracting more and more attention as a novel strategy of antitumor immunotherapy. BsAb not only offers an effective linkage between therapeutics (e.g., immune effector cells, radionuclides and targets (e.g., tumor cells but also simultaneously blocks two different oncogenic mediators. In recent decades, a variety of BsAb formats have been generated. According to the structure of Fc domain, BsAb can be classified into two types: IgG-like format and Fc-free format. Among these formats, bispecific T cell engagers (BiTEs and triomabs are commonly investigated. BsAb has achieved an exciting breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. In this review, we focus on the preclinical experiments and clinical studies of epithelial cell adhesion molecule (EpCAM, human epidermal growth factor receptor (HER family, carcinoembryonic antigen (CEA, and prostate-specific membrane antigen (PSMA related BsAbs in solid tumors, as well as discuss the challenges and corresponding approaches in clinical application.

New Chimeric Antigen Receptor Design for Solid Tumors

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Yuedi Wang

2017-12-01

Full Text Available In recent years, chimeric antigen receptor (CAR T-cell therapy has become popular in immunotherapy, particularly after its tremendous success in the treatment of lineage-restricted hematologic cancers. However, the application of CAR T-cell therapy for solid tumors has not reached its full potential because of the lack of specific tumor antigens and inhibitory factors in suppressive tumor microenvironment (TME (e.g., programmed death ligand-1, myeloid-derived suppressor cells, and transforming growth factor-β. In this review, we include some limitations in CAR design, such as tumor heterogeneity, indefinite spatial distance between CAR T-cell and its target cell, and suppressive TME. We also summarize some new approaches to overcome these hurdles, including targeting neoantigens and/or multiple antigens at once and depleting some inhibitory factors.

Analysis of the value of imaging in diagnosing pancreatic solid-pseudopapillary tumor

International Nuclear Information System (INIS)

Sun Canhui; Li Ziping; Meng Quanfei; Feng Shiting; Fan Miao; Peng Zhenpeng

2007-01-01

Objective: To describe the imaging features of solid-pseudopapillary tumor of the pancreas(SPTP) and evaluate the value of imaging in diagnosing SPTP. Methods: The imaging appearances in seven cases of SPTP confirmed by surgery and pathology were analyzed retrospectively. The un-enhanced and biphasic enhanced CT scanning were per- formed on all seven cases, including gastrointestinal barium meal series on three cases, endoscopic ultrasonography (EUS) on three cases, and MRI on one case. Results All tumors presented well-encapsulated heterogeneous soft tissue mass with varying degrees of solid and cystic components. Barium meal examination showed displaced gastrointestinal wall due to the tumoral compression. EUS demonstrated hyper-echoic mass with scattered small anechoic areas within the tumor. The tumor capsules were hyper-echoic. On un-enhanced CT, the mass appeared hypo-dense with mixed solid and cystic portions in six cases, and with predominantly cystic portion in one case. Calcification appeared in two cases. On biphasic enhanced CT, the mass showed peripheral and heterogeneous enhancement. Three tumors showed marked enhancement, and four tumors showed mild enhancement. Multiple small vessels within the tumor revealed on the arterial phase scanning in one case. The tumor capsules showed discontinuous enhancement in three cases. On T 1 WI, the mass appeared heterogeneous and predominantly isodense. On T 2 WI, the mass appeared heterogeneous and predominantly hyper-dense. The tumor capsule was hypo-dense on T 1 WI and T 2 WI. The mild dilatation of the biliary tract and pancreatic duct was revealed in two cases, respectively. Conclusion: Both CT and MRI can describe characteristic features of SPTP well, and should be used as the main diagnostic methods for SPTP before operation. (authors)

Studies on keV and eV electrons in solids

International Nuclear Information System (INIS)

Schou, J.

1979-10-01

The interaction between keV or eV electrons and solids was studied. The results presented mostly concern problems in connection with electron irradiation of solids, but to some extent they also include ion-induced secondary electron emission. The experiments were mainly performed on solidified gases using 1 - 3 keV electrons. The projected range of electrons was determined in solid hydrogen, deuterium and nitrogen. The true secondary electron emission coefficient and the electron reflection coefficient of solid hydrogen, deuterium and nitrogen were measured. The escape depth of the true secondary electrons in nitrogen was determined. The angular dependence of both the reflection coefficient and the true secondary electron emission coefficient of solid hydrogen and deuterium was investigated. Both ion- and electron-induced secondary electron emission were treated theoretically on the basis of ionization cascade theory. (Auth.)

Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities.

Science.gov (United States)

Xia, An-Liang; Wang, Xiao-Chen; Lu, Yi-Jun; Lu, Xiao-Jie; Sun, Beicheng

2017-10-27

Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have been shown to have unprecedented efficacy in B cell malignancies, most notably in B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate using anti-CD19 CAR-T cells. However, CAR T-cell therapy for solid tumors currently is faced with numerous challenges such as physical barriers, the immunosuppressive tumor microenvironment and the specificity and safety. The clinical results in solid tumors have been much less encouraging, with multiple cases of toxicity and a lack of therapeutic response. In this review, we will discuss the current stats and challenges of CAR-T cell therapy for solid tumors, and propose possibl e solutions and future perspectives.

Photoirradiation system for solid tumors in photodynamic therapy

International Nuclear Information System (INIS)

Pacheco, L.; Stolik, S.; Rosa, J.M. de la

2012-01-01

Photodynamic therapy (PDT) is a clinical procedure which induces cell death for destroying cancerous tissues mostly. This is accomplished by photochemical reaction produced by the combined action of three elements: photo sensitizer, light and oxygen. One aspect of the development of PDT is focused on the treatment of solid and deep tumors, where a set of delivering-light probes are placed into the tumor mass. However, this technique still has several challenges, for although certain parameters involved in the procedure may be adjusted, the complex geometry and non-homogeneity of a tumor difficult to establish the appropriate treatment planning. This paper addresses an overview of interstitial PDT and presents our proposal of photo irradiation system. (Author)

Solid pancreatic pseudopapillary tumor managed laparoscopically: A case report and review of the literature

Directory of Open Access Journals (Sweden)

D. Cuccurullo

Full Text Available Background: Solid pancreatic pseudopapillary tumors are a rare neoplasms, about 1–3% of all pancreatic neoplasms. This cancer mainly affects women between the third and fourth decade of life.They are not well known; the molecular origins represent a low degree of malignancy, in which the complete resection is curative. We report our experience with a case report of SPT in a young man. Presentation of case: Thirty-six years old male patient with a mass about 10 cm in the pancreatic tail and splenic ilum. After following CT and MR, the patient was subjected to surgery. Histophatological result was solid tumor pseudopapillary of pancreas with no pathological lymph nodes. Discussion and conclusion: Solid pseudopapillary neoplasm shows histological characteristic solid and pseudopapillary proliferation. Immunohistochemistry detects, among the causes of tumor development, a correlation between the Beta-catenin mutations, alteration of the E-cadherin. In the most cases, therapy is surgical treatment with laparoscopic. Keywords: Pancreatic pseudopapillary neoplasm, Pancreatic tumor, Laparoscopic surgery

Some epidemiological and clinical characteristics of solid malignant tumors in children from Las Tunas

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Silvio Laffita Estévez

2015-11-01

Full Text Available Background: cancer has kept up as the second cause of death in Las Tunas pediatric population.Objective: to characterize clinical and epidemiological variables of the cases diagnosed with solid malignant tumors in children seen and treated in the onco-pediatric consultation of “Mártires de Las Tunas” Pediatric Hospital from 2010 to 2014.Methods: a descriptive and retrospective study was carried out in 62 patients with solid malignant tumors in the pediatric population of Las Tunas province, from January, 2010 to December, 2014. The variables considered were: presumptive diagnosis, age, family history of tumors, clinical signs of alarm related to the tumor at the moment of diagnosis and investigations to confirm the diagnosis.  Results: non-Hodgkin lymphoma was the most frequently diagnosed tumor, with a 19, 35% of the patients. The most affected age group was between 11 and 14 years old, with a 33, 87%. The 16, 13% of the patients had family history of solid malignant tumors. The most frequent form of presentation was the abdominal tumor, with 29, 03 %. Abdominal ultrasound and computerized axial tomography were the most used complementary diagnostic means, both in the 17, 74% of the patients. Biopsy was used to confirm the 96, 77% of the cases.Conclusions: the clinical and epidemiological variables were characterized in pediatric patients diagnosed with solid malignant tumors in Las Tunas. Children between 11 and 14 years old and family history of malignant tumors were the most significant findings.

Angiogenesis and anti-angiogenesis: Perspectives for the treatment of solid tumors

NARCIS (Netherlands)

Hinsbergh, V.W.M. van; Collen, A.; Koolwijk, P.

1999-01-01

Angiogenesis is the formation of new blood vessels from preexisting ones. Many solid tumors depend on an extensive newly formed vascular network to become nourished and to expand. Tumor cells induce the formation of an extensive but aberrant vascular network by the secretion of angiogenic factors. A

Electron drift in a large scale solid xenon

International Nuclear Information System (INIS)

Yoo, J.; Jaskierny, W.F.

2015-01-01

A study of charge drift in a large scale optically transparent solid xenon is reported. A pulsed high power xenon light source is used to liberate electrons from a photocathode. The drift speeds of the electrons are measured using a 8.7 cm long electrode in both the liquid and solid phase of xenon. In the liquid phase (163 K), the drift speed is 0.193 ± 0.003 cm/μs while the drift speed in the solid phase (157 K) is 0.397 ± 0.006 cm/μs at 900 V/cm over 8.0 cm of uniform electric fields. Therefore, it is demonstrated that a factor two faster electron drift speed in solid phase xenon compared to that in liquid in a large scale solid xenon

Nutritional status changes in children with malignant solid tumor before and after chemotherapy

OpenAIRE

Boris Januar; Sri S Nasar; Rulina Suradi; Maria Abdulsalam

2016-01-01

Background Although aggressive multimodal treatment programs in childhood cancer have significantly increased survival rates, the morbidity caused by protein energy malnutrition related to therapy is still high. Objective To describe nutritional status changes in children with malignant solid tumors after 21 days of chemotherapy. Methods A descriptive prospective study with pre- and post-test design in children with malignant solid tumors was conducted in the Departmen...

Using a 3-d model system to screen for drugs effective on solid tumors

OpenAIRE

Fayad, Walid

2011-01-01

There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward.

Science.gov (United States)

Li, Jian; Li, Wenwen; Huang, Kejia; Zhang, Yang; Kupfer, Gary; Zhao, Qi

2018-02-13

Recently, the US Food and Drug Administration (FDA) approved the first chimeric antigen receptor T cell (CAR-T) therapy for the treatment CD19-positive B cell acute lymphoblastic leukemia. While CAR-T has achieved remarkable success in the treatment of hematopoietic malignancies, whether it can benefit solid tumor patients to the same extent is still uncertain. Even though hundreds of clinical trials are undergoing exploring a variety of tumor-associated antigens (TAA), no such antigen with comparable properties like CD19 has yet been identified regarding solid tumors CAR-T immunotherapy. Inefficient T cell trafficking, immunosuppressive tumor microenvironment, suboptimal antigen recognition specificity, and lack of safety control are currently considered as the main obstacles in solid tumor CAR-T therapy. Here, we reviewed the solid tumor CAR-T clinical trials, emphasizing the studies with published results. We further discussed the challenges that CAR-T is facing for solid tumor treatment and proposed potential strategies to improve the efficacy of CAR-T as promising immunotherapy.

AKT Inhibition in Solid Tumors With AKT1 Mutations.

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Hyman, David M; Smyth, Lillian M; Donoghue, Mark T A; Westin, Shannon N; Bedard, Philippe L; Dean, Emma J; Bando, Hideaki; El-Khoueiry, Anthony B; Pérez-Fidalgo, José A; Mita, Alain; Schellens, Jan H M; Chang, Matthew T; Reichel, Jonathan B; Bouvier, Nancy; Selcuklu, S Duygu; Soumerai, Tara E; Torrisi, Jean; Erinjeri, Joseph P; Ambrose, Helen; Barrett, J Carl; Dougherty, Brian; Foxley, Andrew; Lindemann, Justin P O; McEwen, Robert; Pass, Martin; Schiavon, Gaia; Berger, Michael F; Chandarlapaty, Sarat; Solit, David B; Banerji, Udai; Baselga, José; Taylor, Barry S

2017-07-10

Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and plasma cell-free DNA (cfDNA) were collected in the majority of patients to identify predictive biomarkers of response. Results In patients with AKT1 E17K-mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor-positive breast, gynecologic, and other solid tumors, respectively. In an exploratory biomarker analysis, imbalance of the AKT1 E17K-mutant allele, most frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045). Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR, 0.18; P = .004) and response ( P = .025). Responses were not restricted to patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade ≥ 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%). Conclusion This study provides the first clinical data that AKT1 E17K is a therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation further conditioned response to AZD5363.

Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor

International Nuclear Information System (INIS)

Monzen, Hajime; Griffin, R.J.; Williams, B.W.; Amamo, Morikazu; Ando, Satoshi; Hasegawa, Takeo

2004-01-01

Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging (MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H and E) staining. Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an intraperitoneal (i.p.) injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor. (author)

Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors

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Hamidreza Namazi

2016-01-01

Full Text Available Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.

Strategies for enhancing adoptive T-cell immunotherapy against solid tumors using engineered cytokine signaling and other modalities.

Science.gov (United States)

Shum, Thomas; Kruse, Robert L; Rooney, Cliona M

2018-05-04

Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms. Areas covered: We summarize the latest developments in engineered T-cell immunotherapy, describe the limitations of these approaches in treating solid tumors, and finally highlight several strategies that may be useful in mediating solid tumor responses in the future, while also ensuring safety of engineered cells. Expert opinion: CAR-T therapies require further engineering to achieve their potential against solid tumors. Facilitating cytokine signaling in CAR T-cells appears to be essential in achieving better responses. However, the engineering of T-cells with potentially unchecked proliferation and potency raises the question of whether the simultaneous combination of enhancements will prove safe, necessitating continued advancements in regulating CAR-T activity at the tumor site and methods to safely switch off these engineered cells.

Secondary electron emission from solid HD and a solid H2-D2 mixture

DEFF Research Database (Denmark)

Sørensen, H.; Børgesen, P.; Hao-Ming, Chen

1983-01-01

Secondary electron emission from solid HD and a solid 0.6 H2 + 0.4 D2 mixture has been studied for electron and hydrogen ion bombardment at primary energies from 0.5 to 3 keV and 2 to 10 keV/amu, respectively. The yield for solid HD is well explained by a simple stoichiometric model of the low...

Scanning electron microscopy of primary bone tumors

International Nuclear Information System (INIS)

Pool, R.R.; Kerner, B.

1975-01-01

Critical-point-drying of tumor tissue fixed in a glutaraldehyde-paraformaldehyde solution and viewed by scanning electron microscopy (SEM) provides a 3-dimensional view of tumor cells and their matrices. This report describes the SEM appearance of three primary bone tumors: a canine osteosarcoma of the distal radius, a feline chondrosarcoma of the proximal tibia and a canine fibrosarcoma of the proximal humerus. The ultrastructural morphology is compared with the histologic appearance of each tumor

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

Science.gov (United States)

Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

Observation of strongly forbidden solid effect dynamic nuclear polarization transitions via electron-electron double resonance detected NMR

Energy Technology Data Exchange (ETDEWEB)

Smith, Albert A.; Corzilius, Björn; Haze, Olesya; Swager, Timothy M.; Griffin, Robert G., E-mail: rgg@mit.edu [Department of Chemistry and Francis Bitter Magnet Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States)

2013-12-07

We present electron paramagnetic resonance experiments for which solid effect dynamic nuclear polarization transitions were observed indirectly via polarization loss on the electron. This use of indirect observation allows characterization of the dynamic nuclear polarization (DNP) process close to the electron. Frequency profiles of the electron-detected solid effect obtained using trityl radical showed intense saturation of the electron at the usual solid effect condition, which involves a single electron and nucleus. However, higher order solid effect transitions involving two, three, or four nuclei were also observed with surprising intensity, although these transitions did not lead to bulk nuclear polarization—suggesting that higher order transitions are important primarily in the transfer of polarization to nuclei nearby the electron. Similar results were obtained for the SA-BDPA radical where strong electron-nuclear couplings produced splittings in the spectrum of the indirectly observed solid effect conditions. Observation of high order solid effect transitions supports recent studies of the solid effect, and suggests that a multi-spin solid effect mechanism may play a major role in polarization transfer via DNP.

Convoy electron production by heavy ions in solids

International Nuclear Information System (INIS)

Sellin, I.A.

1984-01-01

The term convoy electron refers to those electrons ejected in fast ion-atom and ion-solid collisions closely matched in vector velocity to that of the incident heavy particles responsible for their ejection. Similarities and differences among electrons ejected into such states through binary electron capture to continuum and electron loss to continuum processes in single ion-atom encounters are compared and contrasted to more complex ejection processes occurring in solid targets. Puzzles posed by the apparent strong projectile Z dependence but weak emergent ion charge dependence of the yield in the case of solid targets are reviewed. Very recent progress in resolving these puzzles has been made by recent observations that the apparent mean free path for electron scattering out of the forward direction within the target is observed to be an order of magnitude greater than that for free electrons of equal velocity provided the projectile charge is high. 13 references, 2 figures, 1 table

Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

OpenAIRE

Kelly, K; Infante, JR; Taylor, MH; Patel, MR; Wong, DJ; Iannotti, N; Mehnert, JM; Loos, AH; Koch, H; Speit, I; Gulley, JL

2018-01-01

© 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. BACKGROUND: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. METHODS: Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patient...

Uptake of labelled tallysomycin by solid Ehrlich ascites tumors in mice

International Nuclear Information System (INIS)

Liniecki, J.; Rembelska, M.; Koniarek, B.

1983-01-01

Tumor and normal tissue uptake of 51 Cr- or 57 Co-labelled bleomycin (BLEO) and tallysomycin (TLM) was compared in female solid Ehrlich ascites tumor mice of Swiss strain. The complexes were administered intraperitoneally: 30-50 μg of each complex with an activity of 40-120 μCi. Activity distribution factors (ADF) and tumor/non-tumor ratios for blood, bone, skeletal muscles, kidneys and liver were determined. The ratios were generally higher for complexes labelled with 57 Co than for the 51 Cr-labelled ones; bleomycin appears equivalent or superior to tallysomycin. (orig.) [de

Advances in Cancer Immunotherapy in Solid Tumors

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Smitha Menon

2016-11-01

Full Text Available Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field.

Characterization of cell suspensions from solid tumors

International Nuclear Information System (INIS)

Pallavicini, M.

1985-01-01

The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs

Evaluation of malignant solid tumor in childhood with FDG-PET

International Nuclear Information System (INIS)

Ishida, Amane; Goto, Hiroaki; Kuroki, Fumiko

2006-01-01

Usefulness of FDG-PET (18F-deoxyglucose PET) was examined in evaluation of diagnosis and therapeutic efficacy of childhood malignant solid tumors. Subjects were 32 patients (16 males) of the median age of 7 y (1 - 27 y), involving those with neuroblastoma (9 cases), hepatoblastoma (4), chronic granulomatous disorder (4) and others (each ≤2). They underwent 75 FDG-PET examinations for diagnosis before and during treatment in authors' hospital in the period from May 2001 to December 2003. Standard uptake value (SUV), 1 x 1 cm region of interest (ROI) of abnormally high distribution area of radioactivity in the lesion/FDG dose/kg body wt., was used for evaluation: SUV>1.5 was defined positive. In neuroblastoma, FDG was found to be highly distributed and kinetics of SUV, to be useful for evaluation of therapeutic efficacy and early metastasis detection. In some cases of hepatoblastoma, the therapeutic effectiveness and recurrence were not satisfactorily evaluative. The distribution of FDG was not satisfactory in Wilms' tumor relative to other tumors. The PET was thought to be useful, despite their small case number examined, for those evaluations of Ewing's tumor, dysgerminoma and Langerhans cell histiocytosis. Thus FDG-PET was found useful for detection, evaluation of therapeutic efficacy and early metastasis detection of pediatric malignant solid tumors. (T.I.)

Recombinant Immunotoxin Therapy of Solid Tumors: Challenges and Strategies.

Science.gov (United States)

Shan, Liang; Liu, Yuanyi; Wang, Paul

2013-01-01

Immunotoxins are a group of protein-based therapeutics, basically comprising two functional moieties: one is the antibody or antibody Fv fragment that allows the immunotoxin to bind specifically to target cells; another is the plant or bacterial toxin that kills the cells upon internalization. Immunotoxins have several unique features which are superior to conventional chemotherapeutics, including high specificity, extraordinary potency, and no known drug resistance. Development of immunotoxins evolves with time and technology, but significant progress has been achieved in the past 20 years after introduction of recombinant DNA technique and generation of the first single-chain variable fragment of monoclonal antibodies. Since then, more than 1,000 recombinant immunotoxins have been generated against cancer. However, most success in immunotoxin therapy has been achieved against hematological malignancies, several issues persist to be significant barriers for effective therapy of human solid tumors. Further development of immunotoxins will largely focus on the improvement of penetration capability to solid tumor mass and elimination of immunogenicity occurred when given repeatedly to patients. Promising strategies may include construction of recombinant antibody fragments with higher binding affinity and stability, elimination of immunodominant T- and B-cell epitopes of toxins, modification of immunotoxins with macromolecules like poly(ethylene glycol) and liposomes, and generation of immunotoxins with humanized antibody fragments and human endogenous cytotoxic enzymes. In this paper, we briefly reviewed the evolution of immunotoxin development and then discussed the challenges of immunotoxin therapy for human solid tumors and the potential strategies we may seek to overcome the challenges.

Electron emission from solids induced by swift heavy ions

International Nuclear Information System (INIS)

Xiao Guoqing

2000-01-01

The recent progresses in experimental and theoretical studies of the collision between swift heavy ion and solids as well as electron emission induced by swift heavy ion in solids were briefly reviewed. Three models, Coulomb explosion, thermal spike and repulsive long-lived states, for interpreting the atomic displacements stimulated by the electronic energy loss were discussed. The experimental setup and methods for measuring the electron emission from solids were described. The signification deviation from a proportionality between total electron emission yields and electronic stopping power was found. Auger-electron and convoy-electron spectra are thought to be a probe for investigating the microscopic production mechanisms of the electronic irradiation-damage. Electron temperature and track potential at the center of nuclear tracks in C and polypropylene foils induced by 5 MeV/u heavy ions, which are related to the electronic excitation density in metals and insulators respectively, were extracted by measuring the high resolution electron spectra

L-Asparaginase delivered by Salmonella typhimurium suppresses solid tumors

Directory of Open Access Journals (Sweden)

Kwangsoo Kim

Full Text Available Bacteria can be engineered to deliver anticancer proteins to tumors via a controlled expression system that maximizes the concentration of the therapeutic agent in the tumor. L-asparaginase (L-ASNase, which primarily converts asparagine to aspartate, is an anticancer protein used to treat acute lymphoblastic leukemia. In this study, Salmonellae were engineered to express L-ASNase selectively within tumor tissues using the inducible araBAD promoter system of Escherichia coli. Antitumor efficacy of the engineered bacteria was demonstrated in vivo in solid malignancies. This result demonstrates the merit of bacteria as cancer drug delivery vehicles to administer cancer-starving proteins such as L-ASNase to be effective selectively within the microenvironment of cancer tissue.

Approaches to drug resistance in solid tumors : with emphasis on lung cancer

NARCIS (Netherlands)

Bakker, Marleen

2005-01-01

De novo or acquired resistance of tumor cells to anticancer agents remains a major problem for the therapeutic efficacy of chemotherapeutic drugs. Most solid tumors are intrinsically insensitive or acquire resistance after initial response to chemotherapy. Different mechanisms seem to play a role in

Electronic structure of elements and compounds and electronic phases of solids

International Nuclear Information System (INIS)

Nadykto, B.A.

2000-01-01

The paper reviews technique and computed energies for various electronic states of many-electron multiply charged ions, molecular ions, and electronic phases of solids. The model used allows computation of the state energy for free many-electron multiply charged ions with relative accuracy ∼10 -4 suitable for analysis of spectroscopy data

Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

Science.gov (United States)

Yu, Man; Lee, Carol; Wang, Marina; Tannock, Ian F

2015-10-01

Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration-dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Immunoconjugates against solid tumors: mind the gap.

Science.gov (United States)

Ricart, A D

2011-04-01

The objective of immunoconjugate development is to combine the specificity of immunoglobulins with the efficacy of cytotoxic molecules. This therapeutic approach has been validated in hematologic malignancies; however, several obstacles to achieving efficacy in treating solid tumors have been identified. These include insufficient specificity of targets and poor antibody delivery, most specifically to the tumor core. Heterogeneous antigen expression, imperfect vascular supply, and elevated interstitial fluid pressure have been suggested as the factors responsible for the poor delivery of antibodies. Promising immunoconjugates are in development: immunoconjugates targeting the prostate-specific membrane antigen, trastuzumab-DM1, lorvotuzumab mertansine, and SS1P. Advances in cancer biology and antibody engineering may overcome some of the challenges. New small antibody formats, such as single-chain Fv, Fab, and diabodies, may improve penetration within tumor masses. Nevertheless, the cost of treatment might require justification in terms of demonstrable improvement in quality of life in addition to efficacy; further economic evaluation might be necessary before this approach can replace the current standards of care in clinical practice.

Effect of fluid friction on interstitial fluid flow coupled with blood flow through solid tumor microvascular network.

Science.gov (United States)

Sefidgar, Mostafa; Soltani, M; Raahemifar, Kaamran; Bazmara, Hossein

2015-01-01

A solid tumor is investigated as porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multiscale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. The mathematical method involves processes such as blood flow through vessels and solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model predicts.

Four cases of solid pseudopapillary tumors of pancreas: Imaging findings and pathological correlations

International Nuclear Information System (INIS)

Vargas-Serrano, Blanca; Dominguez-Ferreras, Esther; Chinchon-Espino, David

2006-01-01

Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection and that a SPTP had been pathologically proved. Results: Four cases of solid pseudopapillary tumor of the pancreas were diagnosed and treated in our institution in the study period. Two of the patients, developed on follow-up liver metastases, and peritoneal, hepatic, and nodal metastases, respectively. Conclusion: Solid pseudopapillary tumors are well-encapsulated neoplasms that usually have a good prognosis after surgical excision. A malignant behavior is uncommon and in this case lymph node involvement, hepatic metastases and occasionally peritoneal invasion may also occur. Resection of liver metastases can prolong the long-term survival of the patients

Solid-state electronic devices an introduction

CERN Document Server

Papadopoulos, Christo

2014-01-01

A modern and concise treatment of the solid state electronic devices that are fundamental to electronic systems and information technology is provided in this book. The main devices that comprise semiconductor integrated circuits are covered in a clear manner accessible to the wide range of scientific and engineering disciplines that are impacted by this technology. Catering to a wider audience is becoming increasingly important as the field of electronic materials and devices becomes more interdisciplinary, with applications in biology, chemistry and electro-mechanical devices (to name a few) becoming more prevalent. Updated and state-of-the-art advancements are included along with emerging trends in electronic devices and their applications. In addition, an appendix containing the relevant physical background will be included to assist readers from different disciplines and provide a review for those more familiar with the area. Readers of this book can expect to derive a solid foundation for understanding ...

Recent advances in the design of drug-loaded polymeric implants for the treatment of solid tumors.

Science.gov (United States)

Wadee, Ameena; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Penny, Clement; Ndesendo, Valence M K; Kumar, Pradeep; Murphy, Caragh S

2011-10-01

The effective treatment of solid tumors continues to be a great challenge to clinicians, despite the development of novel drugs. In order to improve the clinical efficacy of existing chemotherapeutic agents, researchers have considered the possibility of site-specific solid tumor treatment. The greatest advantage of localized delivery is the significantly fewer side effects experienced by patients. Recently, in situ forming implants have attracted considerable interest. These polymeric systems are injected as solutions into tumor sites and the injected solution forms an implant as a result of local environmental stimuli and hence removes the need for surgical implantation. This review summarizes the attempts that have been made to date in the development of polymeric implants for the treatment of solid tumors. Both in situ forming implants and preformed implants, fabricated using natural and synthetic polymers, are described. In addition, the peri- or intra-tumoral delivery of chemotherapeutic agents based on implants inserted surgically into the affected region is also discussed along with a short coverage of implants having an undesirable initial burst release effect. Although these implants have been shown to improve the treatment of various solid tumors, the ideal implant that is able to deliver high doses of chemotherapeutics to the tumor site, over prolonged periods with relatively few side effects on normal tissue, is yet to be formulated.

Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors

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Brellier Florence

2012-09-01

Full Text Available Abstract Background Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors. Methods We analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues. Results From all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples. Conclusions The present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.

Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps☆

OpenAIRE

Beatty, Gregory L.; O’Hara, Mark

2016-01-01

Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers t...

Targeting the PD-1 pathway in pediatric solid tumors and brain tumors

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Wagner LM

2017-04-01

Full Text Available Lars M Wagner,1 Val R Adams2 1Division of Pediatric Hematology/Oncology, 2Department of Pharmacy Practice and Science, University of Kentucky, Lexington, KY, USA Abstract: While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1 pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies. In this manuscript we review current strategies for targeting the PD-1 pathway, highlighting putative biomarkers and the rationale for investigation of these drugs to treat common pediatric tumors such as sarcoma, neuroblastoma, and high-grade glioma. We summarize the completed and ongoing clinical trial data available, and suggest potential applications for further study. Keywords: PD-1, nivolumab, pembrolizumab, pediatric, sarcoma, neuroblastoma, glioma

Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

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Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

2013-11-15

The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

CBT-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors

Science.gov (United States)

2018-02-07

Solid Tumor; Advanced Cancer; ColoRectal Cancer; Endometrial Cancer; Gastric Cancer; Hepatocellular Cancer; Nonsmall Cell Lung Cancer; Mesothelioma; Ovarian Cancer; Renal Cancer; Nasopharyngeal Cancer; Esophageal Cancer; Gastroesophageal Junction Adenocarcinoma

On Secondary Electron Emission from Solid H2 and D2

DEFF Research Database (Denmark)

Schou, Jørgen; Sørensen, H.

1978-01-01

The emission of secondary electrons from solid hydrogen (H2 , D2, T2) is often considered to be of importance for the interaction between a fusion plasma and pellets of solid hydrogens. A set-up was therefore built for studies of interactions between energetic particles and solid hydrogens. Studies...... of secondary electron emission (SEE) from solid H2 and D2 were made for incidence of electrons up to 3 keV and for incidence of ions of hydrogen, deuterium, and helium up to 10 keV. The measurements were made for normal incidence, and in some cases also for oblique incidence. The SEE coefficients for solid H2...... is always 0.65-0.70 times that for solid D2. This difference is attributed to different losses to vibrational states in H2 and D2 for the low energy electrons. Measurements were also made on solid para-H2 with both electrons and hydrogen ions. There was no difference from the results for normal H2, which...

Orbital approach to the electronic structure of solids

CERN Document Server

Canadell, Enric; Iung, Christophe

2012-01-01

This book provides an intuitive yet sound understanding of how structure and properties of solids may be related. The natural link is provided by the band theory approach to the electronic structure of solids. The chemically insightful concept of orbital interaction and the essential machinery of band theory are used throughout the book to build links between the crystal and electronic structure of periodic systems. In such a way, it is shown how important tools for understandingproperties of solids like the density of states, the Fermi surface etc. can be qualitatively sketched and used to ei

Electrons and Disorder in Solids

CERN Document Server

Gantmakher, VF

2005-01-01

This book has been written for those who study or professionally deal with solid state physics. It contains modern concepts about the physics of electrons in solids. It is written using a minimum of mathematics. The emphasis is laid on various physical models aimed at stimulating creative thinking. The book helps the reader choose the most efficient scheme of an experiment or the optimal algorithm of a calculation. Boltzmann and hopping types of conductivity are compared. Thequalitative theory of weak localization is presented and its links with the true localization and metal-insulator transi

Cytogenetics of solid tumors Revisión de tema Citogenética de tumores sólidos

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José Luis Ramírez Castro

2002-02-01

Full Text Available Cytogenetic analysis of tumors has provided valuable information on the biology of cancer. It has been established that more than half of solid tumors show chromosomal anomalies; therefore, cytogenetic analysis is of great usefulness for diagnostic and prognostic purposes. Identification of recurrent chromosomal anomalies in numerous tumors has been considered as an indicador of clinical importance. Cytogenetic studies in tissue tumors have revealed near 100,000 clonal chromosome abnormalities belonging to more that 30,000 human neoplasms. However, due to technical difficulties in cell cultures, only one third of solid tumors have been cytogenetically characterized. Conventional cytogenetics has been very useful for molecular characterization of new oncogenes and tumor-suppressor genes involved in human tumorigenesis. In this review, some important issues related with tumors of chromosomal etiology, the diverse types of chromosomal anomalies with their frequencies, modern diagnostic techniques as well as their impact on the diagnosis and prognosis of cancer are presented. EL análisis citogenético de tumores ha proporcionado valiosa información sobre la biología del cáncer. Se ha establecido que más de la mitad de los tumores sólidos presentan alteraciones cromosómicas; por lo tanto, el análisis citogenético es de gran utilidad para el diagnóstico y el pronóstico. La identificación de cambios cromosómicos específicos recurrentes en numerosos tumores se considera un indicador de importancia clínica. Los estudios en este campo han revelado cerca de 100.000 alteraciones cromosómicas en más de 30.000 neoplasias humanas. Sin embargo, los tumores sólidos son los menos caracterizados citogenéticamente, sólo una tercera parte del total de ellos, debido a problemas técnicos en los cultivos celulares. La citogenética convencional ha sido muy útil para la posterior caracterización molecular de nuevos oncogenes y genes supresores de

Differentiation between benign and malignant solid pseudopapillary tumor of the pancreas by MDCT

International Nuclear Information System (INIS)

Yin, Qihua; Wang, Mingliang; Wang, Chengsheng; Wu, Zhiyuan; Yuan, Fei; Chen, Kun; Tang, Yonghua; Zhao, Xuesong; Miao, Fei

2012-01-01

Purpose: The purpose of this study was to determine if characteristic features on computed tomographic and (or) magnetic resonance imaging can differentiate benign and malignant solid pseudopapillary neoplasms (SPN). Materials and methods: A total of 82 pathologically diagnosed SPN patients were included. CT and MRI were reviewed by 3 radiologists. Each tumor was analyzed through the clinical and imaging features. Results: The highest occurrence of malignant SPN was observed in the group of patients (11–19 years old) followed by the group of patients (50–65 years old). When the tumor was located in the tail and the size was equal or larger than 6.0 cm, the positive and predictive value, the predictive value, sensitivity and specificity for a malignant SPN were 61.5%, 100%, 100% and 78.6%, respectively. Presence of complete encapsulation was more frequent in benign SPNs, but focal discontinuity in the malignant SPNs. Amorphous or scattered calcifications, all near-solid tumors and presence of upstream pancreatic ductal was found in the benign SPNs. Conclusion: A focal discontinuity of the capsule, large tumor size (>6.0 cm) and a pancreatic tail location may suggest malignancy of SPN. In contrast, tumors with amorphous or scattered calcifications, and all near-solid tumors may be indicative of benignancy. Age (less than 20 or more than 50 years old) is a possible risk factor of SPN. In comparison to other pancreatic neoplasms, such as ductal adenocarcinoma, a complete/incomplete pseudo-capsule, without upstream pancreatic duct dilatation and lymph nodes metastasis, and the presence of internal calcification and hemorrhage are more likely SPN.

Molecular mechanisms for synergistic effect of proteasome inhibitors with platinum-based therapy in solid tumors.

Science.gov (United States)

Chao, Angel; Wang, Tzu-Hao

2016-02-01

The successful development of the proteasome inhibitor bortezomib as an anticancer drug has improved survival in patients with multiple myeloma. With the emergence of the newly US Food and Drug Administration-approved proteasome inhibitor carfilzomib, ongoing trials are investigating this compound and other proteasome inhibitors either alone or in combination with other chemotherapy drugs. However, in solid tumors, the efficacy of proteasome inhibitors has not lived up to expectations. Results regarding the potential clinical efficacy of bortezomib combined with other agents in the treatment of solid tumors are eagerly awaited. Recent identification of the molecular mechanisms (involving apoptosis and autophagy) by which bortezomib and cisplatin can overcome chemotherapy resistance and sensitize tumor cells to anticancer therapy can provide insights into the development of novel therapeutic strategies for patients with solid malignancies. Copyright © 2016. Published by Elsevier B.V.

Space Charge Effect in the Sheet and Solid Electron Beam

Science.gov (United States)

Song, Ho Young; Kim, Hyoung Suk; Ahn, Saeyoung

1998-11-01

We analyze the space charge effect of two different types of electron beam ; sheet and solid electron beam. Electron gun simulations are carried out using shadow and control grids for high and low perveance. Rectangular and cylindrical geometries are used for sheet and solid electron beam in planar and disk type cathode. The E-gun code is used to study the limiting current and space charge loading in each geometries.

Prospective Clinical Study of Precision Oncology in Solid Tumors.

Science.gov (United States)

Sohal, Davendra P S; Rini, Brian I; Khorana, Alok A; Dreicer, Robert; Abraham, Jame; Procop, Gary W; Saunthararajah, Yogen; Pennell, Nathan A; Stevenson, James P; Pelley, Robert; Estfan, Bassam; Shepard, Dale; Funchain, Pauline; Elson, Paul; Adelstein, David J; Bolwell, Brian J

2015-11-09

Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effect of Arrabidaea chica extracts on the Ehrlich solid tumor development

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Ana Flávia C. Ribeiro

2012-04-01

Full Text Available The aim of this study was to investigate the effect of Arrabidaea chica (Humb. & Bonpl. B. Verl., Bignoniaceae, extracts on Ehrlich solid tumor development in Swiss mice. Leaves of A. chica were extracted with two distinct solvents, ethanol and water. The phytochemical analysis of the extracts indicated different classes of secondary metabolites like as anthocyanidins, flavonoids, tannins and saponins. Ethanol (EE and aqueous (AE extracts at 30 mg/kg reduced the development of Ehrlich solid tumor after ten days of oral treatment. The EE group presented increase in neutrophil count, α1 and β globulin values, and decrease of α2 globulin values. Furthermore, EE reduced the percentage of CD4+ T cells in blood but did not alter the percentage of inflammatory mononuclear cells associated with tumor suggesting a direct action of EE on tumor cells. Reduced tumor development observed in AE group was accompanied by a lower percentage of CD4+ T lymphocytes in blood. At the tumor microenvironment, this treatment decreased the percentage of CD3+ T cells, especially due to a reduction of CD8+ T subpopulation and NK cells. The antitumor activity presented by the AE is possibly related to an anti-inflammatory activity. None of the extracts produced toxic effects in animals. In conclusion, the ethanol and aqueous extracts of A. chica have immunomodulatory and antitumor activities attributed to the presence of flavonoids, such as kaempferol. These effects appear to be related to different mechanisms of action for each extract. This study demonstrates the potential of A. chica as an antitumor agent confirming its use in traditional popular medicine.

C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

LENUS (Irish Health Repository)

Shrotriya, Shiva

2015-01-01

A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence.

Eosinophilia in routine blood samples as a biomarker for solid tumor development

DEFF Research Database (Denmark)

Andersen, Christen Bertel L; Siersma, V.D.; Hasselbalch, H.C.

2014-01-01

eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing...... was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. CONCLUSION: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize...... that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution....

Solid pseudopapillary tumor of pancreas with sickle cell trait: A rare case report

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Harish S Permi

2013-01-01

Full Text Available Solid pseudopapillary tumor of pancreas is a rare pancreatic neoplasm affecting young women, has low malignant potential and amenable for surgical excision with good long-term survival. Sickle cell trait is benign condition, which involves one normal beta-globin chain and one HbS chain. Although it is a benign condition, individuals are prone to have rare complications that may predispose to death under certain circumstances. We report a rare coexistence of solid pseudopapillary tumor of pancreas with sickle cell trait in an 18-year-old female who underwent distal pancreatectomy with splenectomy. Histopathological examination and haemoglobin electrophoresis confirmed the diagnosis.

Bone marrow transplantation in aplastic anemia, acute leukemia and solid tumors

International Nuclear Information System (INIS)

Champlin, R.; Feig, S.; Gale, R.P.

1980-01-01

Results of bone marrow transplantation for the treatment of aplastic anemia, acute leukemia and solid tumors in the first 141 patients treated between September 1973 and January 1980 are reviewed. Preparation for transplantation with total body irradiation is described. (Auth.)

Hypoxic cell turnover in different solid tumor lines

International Nuclear Information System (INIS)

Ljungkvist, Anna S.E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

2005-01-01

Purpose: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h

Onconase-induced changes in radiation response and physiological parameters in solid tumors

International Nuclear Information System (INIS)

Lee, I.; Shui, C.; Shogen, K.; Mikulski, S.M.; Nunno, M.; Wallner, P.E.

1996-01-01

Purpose: Onconase (ONC), previously known as P-30 protein, is a novel basic amphibian protein isolated from eggs of the leopard frog. The original study conducted by Darzynkiewicz et al. (Cell Tissue Kinetics, 1988) demonstrated that ONC shows anti-proliferative and cytotoxic activities against several tumor cell lines in vitro. Since then, to our knowledge, no studies regarding the inhibitory effect of ONC in solid tumor models were performed. ONC is also known to inhibit cell-cycle progression from the radiation-sensitive G 1 phase to the radiation-resistant S phase. Thus, we examined the effect of ONC as a potential radiation sensitizer. The radiation response and physiological parameters were evaluated in C3H mice and/or nude mice bearing various (murine and/or human) tumor models. Materials and Method: First, we examined the effect of ONC on the cellular proliferative, as well as the clonogenic, response of various cell lines (i.e., H4IIE rat hepatoma, AsPC-1 human pancreas adenocarcinoma, DU145 human prostate carcinoma, LS174T human colon adenocarcinoma, A549 human lung carcinoma, MCaIV murine adenocarcinoma, FSaII murine fibrosarcoma, and CCL-209 bovine artery pulmonary endothelial cells) by using the MTT and clonogenic cell survival assays. Second, we determined the enhancement of radiation response before, during, and after treatment with ONC in several cell lines. Third, we determined whether ONC can inhibit the growth of solid tumors in vivo (i.e., FSaII and MCaIV in C3H mice, LS174T in nude mice). Fourth, we examined whether minocycline, an antiangiogenic agent, could amplify the tumoricidal efficacy of ONC in solid tumors. To test our hypothesis: if ONC could eradicate the outgrowth of tumor cells in confined spaces, it could lower the elevated pressure in solid tumors, we measured tumor interstitial fluid pressure (TIFP) using the wick-in-needle method, and systemic pressure using the right carotid artery cannulation method after treatment with ONC

Inelastic interactions of swift electrons in solids

International Nuclear Information System (INIS)

Tung, C.J.; Ritchie, R.H.; Ashley, J.C.; Anderson, V.E.

1976-01-01

Theoretical calculations of electron mean free paths and electron slowing-down spectra in solids are described. These calculations involve (a) the use of an electron gas model to approximate the response of conduction band electrons in metals, (b) the application of a statistical model for the calculation of electron mean free paths in metals, (c) the development of an insulator model to describe valence band electrons in insulators and semiconductors, and (d) the use of data on atomic generalized oscillator strengths to describe the excitation of the ion cores. Exchange effects are included in the calculations through a semi-empirical procedure. Detailed results are presented for electron mean free paths in Ag, Au, Al, and Al 2 O 3 , and on the stopping power of Al and Al 2 O 3 , for electrons with energies at a few eV to 10 keV. The agreement of these calculations with experimental measurements is quite reasonable over a wide range of electron energies. A detailed description of the calculation of electron slowing-down spectra in solids is presented. Low energy electron slowing-down spectra of monoenergetic electron sources in Al and Al 2 O 3 are calculated. Calculations of electron slowing-down spectra in Al 2 O 3 are made using differential cross sections obtained employing an insulator model and from GOS functions for ion core electrons. Auger electron contributions to the slowing-down spectrum are discussed. Results for the slowing-down spectrum are compared with the experimental data measured by Birkhoff and coworkers. Generally good agreement is found over a wide range of electron energies

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

International Nuclear Information System (INIS)

Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

2014-01-01

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

Energy Technology Data Exchange (ETDEWEB)

Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

2014-11-04

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

Photodynamic therapy of solid tumors

Science.gov (United States)

Jori, Giulio

Some porphyrin compounds, which are characterized by a relatively large degree of hydrophobicity (n-octanol/water partition coefficient above 8), are accumulated in greater amounts and retained for longer periods of time by neoplastic as compared with normal tissues. The affinity of these dyes for tumors is partially a consequence of their in vivo transport by low-density lipoproteins, which are preferentially endocytosized by hyperproliferating tissues in a receptor-mediated process. In general, at 24-48 h after the systematic administration of porphyrin doses in the range of 2.5 mg/kg body weight, the ratio of drug concentration between the neoplastic and the surrounding tissues is sufficiently large to guarantee a selective photoexcitation of the porphyrin. Toward this aim, the porphyrin-containing tumor tissues are irradiated with light wavelengths longer than 600 nm, since the transmittance of biological tissues is maximal in this spectral region. The electronically excited porphyrin transfers its excitation energy to oxygen, thus generating activated oxygen species (mainly, singlet oxygen): as a consequence, the photooxidative modification of subcellular targets (e.g. the plasma membrane and mitochondria) is readily obtained leading to an irreversible necrosis of the cell. With the most frequently used porphyrins for clinical phototherapy (including hematoporphyrin and its derivatives HpD and Photofrin II), one observes the preferential photosensitized destruction of endothelial cells, hence the vascular damage is a major process involved in the necrosis of tumors. The optimization of the phototherapy of tumors is presently pursued by the definition of clinical protocols tailored to the optical properties of specific neoplastic tissues as well as by the use of porphyrin analogs, such as chlorins and phthalocyanines, having an extinction coefficient in the red spectral region larger than that typical of hematoporphyrin and HpD.

Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

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Katerina T. Xenaki

2017-10-01

Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

Particle dynamics during electronic sputtering of solid krypton

DEFF Research Database (Denmark)

Dutkiewicz, L.; Pedrys, R.; Schou, Jørgen

1995-01-01

We have modeled electronic sputtering of solid krypton by excimer production with molecular dynamics. Both excimer evolution in the solid and deexcitation processes have been incorporated in the simulation. The excimer dynamics in the lattice has been analyzed: the excimers formed near the surface...

Fundamentals of the Physics of Solids Volume 2: Electronic Properties

CERN Document Server

Sólyom, Jenő

2009-01-01

This book is the second of a single-authored, three-volume series that aims to deliver a comprehensive and self-contained account of the vast field of solid-state physics. It goes far beyond most classic texts in the presentation of the properties of solids and experimentally observed phenomena, along with the basic concepts and theoretical methods used to understand them and the essential features of various experimental techniques. The first volume deals with the atomic and magnetic structure and dynamics of solids, the second with those electronic properties that can be understood in the one-particle approximation, and the third with the effects due to interactions and correlations between electrons. This volume is devoted to the electronic properties of metals and semiconductors in the independent-electron approximation. After a brief discussion of the free-electron models by Drude and Sommerfeld, the methods for calculating and measuring the band structure of Bloch electrons moving in the periodic potent...

Chimeric antigen receptor T cells: a novel therapy for solid tumors

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Shengnan Yu

2017-03-01

Full Text Available Abstract The chimeric antigen receptor T (CAR-T cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2, and mesothelin (MSLN, as well as the challenges for CAR-T cell therapy.

An introduction to the electron theory of solids

CERN Document Server

Stringer, John; Hopkins, D W; Finniston, H M

2013-01-01

An Introduction to the Electron Theory of Solids introduces the reader to the electron theory of solids. Topics covered range from the breakdown of classical theory to atomic spectra and the old quantum theory, as well as the uncertainty principle of Heisenberg and the foundations of quantum mechanics. Some problems in wave mechanics and a wave-mechanical treatment of the simple harmonic oscillator and the hydrogen atom are also presented.Comprised of 12 chapters, this book begins with an introduction to Isaac Newton's theory of classical mechanics and how the scientists after him discounted h

Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

Science.gov (United States)

Roy Chaudhuri, Tista

An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

A quantitative theory of solid tumor growth, metabolic rate and vascularization.

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Alexander B Herman

Full Text Available The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed.

Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations.

Science.gov (United States)

Medhat, Dalia; Hussein, Jihan; El-Naggar, Mehrez E; Attia, Mohamed F; Anwar, Mona; Latif, Yasmine Abdel; Booles, Hoda F; Morsy, Safaa; Farrag, Abdel Razik; Khalil, Wagdy K B; El-Khayat, Zakaria

2017-07-01

Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Solid tumors after chemotherapy or surgery for testicular nonseminoma: a population-based study.

Science.gov (United States)

Fung, Chunkit; Fossa, Sophie D; Milano, Michael T; Oldenburg, Jan; Travis, Lois B

2013-10-20

Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy. Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up. Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78). To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility.

Factors associated with abandonment of therapy by children diagnosed with solid tumors in Peru.

Science.gov (United States)

Vasquez, Liliana; Diaz, Rosdali; Chavez, Sharon; Tarrillo, Fanny; Maza, Ivan; Hernandez, Eddy; Oscanoa, Monica; García, Juan; Geronimo, Jenny; Rossell, Nuria

2018-06-01

Abandonment of treatment is a major cause of treatment failure and poor survival in children with cancer in low- and middle-income countries. The incidence of treatment abandonment in Peru has not been reported. The aim of this study was to examine the prevalence of and factors associated with treatment abandonment by pediatric patients with solid tumors in Peru. We retrospectively reviewed the sociodemographic and clinical data of children referred between January 2012 and December 2014 to the two main tertiary centers for childhood cancer in Peru. The definition of treatment abandonment followed the International Society of Paediatric Oncology, Paediatric Oncology in Developing Countries, Abandonment of Treatment recommendation. Data from 1135 children diagnosed with malignant solid tumors were analyzed, of which 209 (18.4%) abandoned treatment. Bivariate logistic regression analysis showed significantly higher abandonment rates in children living outside the capital city, Lima (forest; odds ratio [OR] 3.25; P < 0.001), those living in a rural setting (OR 3.44; P < 0.001), and those whose parent(s) lacked formal employment (OR 4.39; P = 0.001). According to cancer diagnosis, children with retinoblastoma were more likely to abandon treatment compared to children with other solid tumors (OR 1.79; P = 0.02). In multivariate regression analyses, rural origin (OR 2.02; P = 0.001) and lack of formal parental employment (OR 2.88; P = 0.001) were independently predictive of abandonment. Treatment abandonment prevalence of solid tumors in Peru is high and closely related to sociodemographical factors. Treatment outcomes could be substantially improved by strategies that help prevent abandonment of therapy based on these results. © 2018 Wiley Periodicals, Inc.

Interaction between Solid Nitrogen and 1-3-keV Electrons

DEFF Research Database (Denmark)

Schou, Jørgen; Sørensen, H.

1978-01-01

V. At 3 keV, the SEE coefficient is 12 times that for solid deuterium. This is attributed partly to the larger production rate for low-energy electrons in nitrogen and partly to the larger escape probability for these electrons. Moreover, measurements were made of the electron-reflection coefficient, both......Experimental studies were made of the interaction between solid nitrogen and beams of 1-2-keV electrons. The projected range for the electrons was measured by means of the mirror-substrate method (gold substrate), giving the result 9.02×1016 E1.75 molecules/cm2 with the energy given in ke...... for solid nitrogen and for the carbon substrate. For nitrogen, it varied from 0.17 el/el at 1 keV to 0.13 el/el at 3 keV, and for carbon it varied from 0.13 to 0.12. The observations are discussed and comparisons made with other theoretical and experimental results. The agreement ranges from good to fair...

Investigation of particle accumulation, chemosensitivity and thermosensitivity for effective solid tumor therapy using thermosensitive liposomes and hyperthermia

NARCIS (Netherlands)

W.J.M. Lokerse (Wouter); M. Bolkestein (Michiel); T.L.M. ten Hagen (Timo); M. de Jong (Marcel); A.M.M. Eggermont (Alexander); Grüll, H. (Holger); G.A. Koning (Gerben)

2016-01-01

textabstractDoxorubicin (Dox) loaded thermosensitive liposomes (TSLs) have shown promising results for hyperthermia-induced local drug delivery to solid tumors. Typically, the tumor is heated to hyperthermic temperatures (41-42 °C), which induced intravascular drug release from TSLs within the tumor

Anti-m antibody in solid tumors-two case reports.

Science.gov (United States)

Soni, Shiv Kumar; Goyal, Hari; Sood, S K; Setia, Rasika

2014-09-01

Anti-M antibodies are usually of IgM, appear as cold agglutinins and are clinically insignificant. We are reporting two cases of anti-M in cases of solid tumors where the anti-M caused discrepancy in blood grouping, reacted in coombs phase of crossmatching. Anti-M in first case showed dosage effect. These antibodies can be clinical significant when detected in coombs phase, making M antigen negative coombs compatible unit transfusion imperative.

Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model.

Science.gov (United States)

Pishali Bejestani, Elham; Cartellieri, Marc; Bergmann, Ralf; Ehninger, Armin; Loff, Simon; Kramer, Michael; Spehr, Johannes; Dietrich, Antje; Feldmann, Anja; Albert, Susann; Wermke, Martin; Baumann, Michael; Krause, Mechthild; Bornhäuser, Martin; Ehninger, Gerhard; Bachmann, Michael; von Bonin, Malte

2017-01-01

The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model. In addition, we analyzed phenotypic and functional changes of cancer cells and UniCAR-T cells in association with the administration of the targeting module to reveal potential immunoevasive mechanisms. Most notably, UniCAR-T cell activation induced upregulation of immune-inhibitory molecules such as programmed death ligands. In conclusion, this work illustrates that the UniCAR platform mediates potent anti-tumor activity in a relevant in vitro and in vivo solid tumor model.

Induction of oncogene addiction shift to NF-κB by camptothecin in solid tumor cells

International Nuclear Information System (INIS)

Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto; Tsuruo, Takashi; Umezawa, Kazuo; Higashihara, Masaaki; Watanabe, Toshiki; Horie, Ryouichi

2009-01-01

The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-κB activity driven by IκB kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-κB during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-κB inhibitors.

Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

Energy Technology Data Exchange (ETDEWEB)

Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Tsuruo, Takashi [Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Umezawa, Kazuo [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-0061 (Japan); Higashihara, Masaaki [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Watanabe, Toshiki [Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Horie, Ryouichi, E-mail: rhorie@med.kitasato-u.ac.jp [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan)

2009-12-04

The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.

Electron transfer reactions in microporous solids. Progress report, September 1990--January 1993

Energy Technology Data Exchange (ETDEWEB)

Mallouk, T.E.

1993-01-01

Basic thrust the research program involves use of microporous solids (zeolites, clays, layered and tunnel structure oxide semiconductors) as organizing media for artificial photosynthetic systems. Purpose of the microporous solid is twofold. First, it induces spatial organization of photoactive and electroactive components (sensitizers, semiconductor particles, electron relays, and catalysts) at the solid-solution interface, enhancing the quantum efficiency of charge separation and separating physically the ultimate electron donor and acceptor in the electron transport chain. Second, since the microcrystalline solid admits only molecules of a certain charge and size, it is possible to achieve permanent charge separation by sieving chemical photoproducts (e.g., H{sub 2} and I{sub 3}{sup {minus}}, or H{sub 2} and O{sub 2)} from each other. Spectroscopic and electrochemical methods are used to study the kinetics of electron transfer reactions in these hybrid molecular/solid state assemblies.

Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

Directory of Open Access Journals (Sweden)

C.M. Souza

2014-10-01

Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

Evaluating the Needs of Patients Living With Solid Tumor Cancer: A Survey Design.

Science.gov (United States)

Schmidt, April L; Lorenz, Rebecca A; Buchanan, Paula M; McLaughlin, Laura

2018-03-01

To describe the unmet needs of adult patients living with solid tumor cancer. Survey design. Adult patients living with solid tumor cancer from two outpatient clinics were mailed the Sheffield Profile for Assessment and Referral to Care, a holistic screening questionnaire for assessing palliative care needs, and a demographics questionnaire. One hundred fifteen patients returned the instruments, corresponding to a 62% response rate. There were no significant differences by cancer type (breast, non-breast) or gender. However, Caucasians reported significantly more psychological issues, such as anxiety, than non-Caucasians ([ n = 101 (87.8%)] and [ n = 14 (12.2%)], respectively, p = .032). Older patients reported more concerns about loss of independence/activity ( p = .012) compared with younger age groups. Patients living with Stage III/IV cancer reported more distressed about independence/activity ( p = .034), family/social issues ( p = .007), and treatment side effects ( p = .027) than patients living with Stage I/II cancer. Patients living with solid tumor cancer have a myriad of unmet needs regardless of age, gender, cancer type, or cancer stage. There appears to be important differences by cancer stage. The Sheffield Profile for Assessment and Referral to Care questionnaire provides a holistic approach for nurses to identify unmet needs and concerns. Future research should explore the preferred methods of receiving support and information.

Solid waste electron beam treatment

International Nuclear Information System (INIS)

Chmielewski, A.G.

1998-01-01

The possible applications of electron accelerators for solid waste treatment are discussed in the report. The elaborated technologies allow to recycle of materials (e.g. cellulosic materials in municipal waste), improve their hygienic standards (agricultural usage of sludge from municipal waste water treatment) and reduce harmful to environment chemical usage (cellulose degradation). These are environment friendly advanced technologies which meets demands waste recycling. (author)

Solid waste electron beam treatment

Energy Technology Data Exchange (ETDEWEB)

Chmielewski, A G

1998-07-01

The possible applications of electron accelerators for solid waste treatment are discussed in the report. The elaborated technologies allow to recycle of materials (e.g., cellulosic materials in municipal waste), improve their hygienic standards (agricultural usage of sludge from municipal waste water treatment) and reduce harmful to environment chemical usage (cellulose degradation). These are environment friendly advanced technologies which meets demands waste recycling. (author)

Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

Science.gov (United States)

Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

2018-01-01

The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors.

Science.gov (United States)

Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Sheehan, Christine E; Vallabhajosula, Shankar; Goldsmith, Stanley J; Ross, Jeffrey S; Bander, Neil H

2007-02-10

Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response. Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues. Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment. Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

Biochemical parameters of bone metabolism in bone metastases of solid tumors (Review)

NARCIS (Netherlands)

Meijer, Wilhelmus; van der Veer, E; Willemse, P H

1998-01-01

The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and

Ab initio calculation of electron excitation energies in solids

International Nuclear Information System (INIS)

Louie, S.G.

1996-02-01

Progress in the first-principles calculation of electron excitation energies in solids is discussed. Quasiparticle energies are computed by expanding the electron self energy to first order in the screened Coulomb interaction in the so-called GW approximation. The method was applied to explain and predict spectroscopic properties of a variety of systems. Several illustrative applications to semiconductors, materials under pressure, chemisorption, and point defects in solids are presented. A recent reformulation of the method employing mixed- space functions and imaginary time techniques is also discussed

Serum cross-linked n-telopeptides of type 1 collagen (NTx in patients with solid tumors

Directory of Open Access Journals (Sweden)

Fernando Jablonka

Full Text Available CONTEXT AND OBJECTIVE: Cross-linked N-telopeptides of type I collagen (NTx increase in concentration in situations in which bone resorption is increased, such as osteoporosis and bone metastasis (BM. We aimed to evaluate the serum concentrations of NTx in a sample of patients with several types of solid tumors. DESIGN AND SETTING: Cross-sectional analytical study with a control group in a tertiary public hospital. METHODS: We performed the quantitative enzyme-linked immunosorbent assay (ELISA on serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors who had been referred for a bone scan. Three experienced analysts read all bone scans. RESULTS: The serum NTx levels in patients with cancer and BM, with cancer but without BM and without cancer were 46.77 ± 2.58, 32.85 ± 2.05 and 22.32 ± 2.90 respectively (P < 0.0001. We did not find any significant correlations of serum NTx with age, gender, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (R² = 0.08; P = 0.022. CONCLUSIONS: Serum NTx levels are significantly higher in patients with solid tumors and bone metastases than they are in patients without bone metastases and in normal controls.

Outcome for children with metastatic solid tumors over the last four decades.

Directory of Open Access Journals (Sweden)

Stephanie M Perkins

Full Text Available Outcomes for pediatric solid tumors have significantly improved over the last 30 years. However, much of this improvement is due to improved outcome for patients with localized disease. Here we evaluate overall survival (OS for pediatric patients with metastatic disease over the last 40 years.The United States Surveillance, Epidemiology, and End Results (SEER database was used to conduct this study. Patients diagnosed between 0 and 18 years of age with metastatic Ewings sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma or Wilms tumor were included in the analysis.3,009 patients diagnosed between 1973-2010 met inclusion criteria for analysis. OS at 10 years for patients diagnosed between 1973-1979, 1980-1989, 1990-1999 and 2000-2010 was 28.3%, 37.2%, 44.7% and 49.3%, respectively (p<0.001. For patients diagnosed between 2000-2010, 10-year OS for patients with Ewing sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma and Wilms tumor was 30.6%, 54.4%, 29.3%, 27.5%, and 76.6%, respectively, as compared to 13.8%, 25.1%, 13.6%, 17.9% and 57.1%, respectively, for patients diagnosed between 1973-1979. OS for neuroblastoma significantly increased with each decade. For patients with osteosarcoma and Ewing sarcoma, there was no improvement in OS over the last two decades. There was no improvement in outcome for patients with rhabdomyosarcoma or Wilms tumor over the last 30 years.OS for pediatric patients with metastatic solid tumors has significantly improved since the 1970s. However, outcome has changed little for some malignancies in the last 20-30 years. These data underscore the importance of continued collaboration and studies to improve outcome for these patients.

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

Directory of Open Access Journals (Sweden)

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.

Secondary electrons as probe of preequilibrium stopping power of ions penetrating solids

International Nuclear Information System (INIS)

Kroneberger, K.; Rothard, H.; Koschar, P.; Lorenzen, P.; Groeneveld, K.O.; Clouvas, A.; Veje, E.; Kemmler, J.

1990-01-01

The passage of ions through solid media is accompanied by the emission of low energy secondary electrons. At high ion velocities v p (i.e. v p > 10 7 cm/s) the kinetic emission of electrons as a result of direct Coulomb interaction between the ion and the target electron is the dominant initial production mechanism. The energy lost by the ion and, thus, transferred to the electrons is known as electronic stopping power in the solid. Elastic and inelastic interactions of primary, liberated electrons on their way through the bulk and the surface of the solid modify strongly their original energy and angular distribution and, in particular, leads to the transfer of their energy to further, i.e. secondary electrons (SE), such that the main part of the deposited energy of the ion is eventually over transferred to SE. It is, therefore, suggestive to assume a proportionality between the electronic stopping power S sm-bullet of the ion and the total SE yield g, i.e. the number of electrons ejected per ion. Following Sternglass the authors consider schematically for kinetic SE emission contributions from two extreme cases: (a) SEs produced mostly isotropically with large impact parameter, associated with an escape depth L SE from the solid; (b) SEs produced mostly unisotropically in forward direction with small impact parameter (δ-electrons), associated with a transport length L δ

Electronic excitations in fast ion-solid collisions

International Nuclear Information System (INIS)

Burgdoerfer, J.

1990-01-01

We review recent developments in the study of electronic excitation of projectiles in fast ion-solid collisions. Our focus will be primarily on theory but experimental advances will also be discussed. Topics include the evidence for velocity-dependent thresholds for the existence of bound states, wake-field effects on excited states, the electronic excitation of channeled projectiles, transport phenomena, and the interaction of highly charged ions with surfaces. 44 refs., 14 figs

Electron Hole Plasma in Solids Induced by Ultrashort XUV Laser Pulses

International Nuclear Information System (INIS)

Rethfeld, B.; Medvedev, N.

2013-01-01

Irradiation of solids with ultrashort XUV laser pulses leads to an excitation of electrons from the valence band and deeper shells to the conduction band leading to a nonequilibrium highly energetic electron hole plasma. We investigate the transient electron dynamics in a solid semiconductor and metal (silicon and aluminum, respectively) under irradiation with a femtosecond VUV to XUV laser pulse as used in experiments with the Free Electron Laser FLASH at DESY in Hamburg, Germany. Applying the Asymptotical Trajectory Monte-Carlo technique, we obtain the transient energy distribution of the excited and ionized electrons within the solid. Photon absorption by electrons in different bands and secondary excitation and ionization processes are simulated event by event. The method was extended in order to take into account the electronic band structure and Pauli's principle for electrons in the conduction band. In this talk we review our results on the dynamics of the transient electron-hole plasma, in particular its transient density and energy distribution in dependence on laser and material parameters. For semiconductors we introduce the concept of an ''effective energy gap'' for collective electronic excitation, which can be applied to estimate the free electron density after high-intensity ultrashort XUV laser pulse irradiation. For aluminum we demonstrate that the electronic spectra depend on the relaxation kinetics of the excited electronic subsystem. Experimentally observed spectra of emitted photons from irradiated aluminum can be explained well with our results. (author)

Anxiety, depression in patients receiving chemotherapy for solid tumors

International Nuclear Information System (INIS)

Mansoor, S.; Jehangir, S.

2015-01-01

To determine the frequency of anxiety and depression in patients undergoing chemotherapy for solid tumors using Hospital Anxiety Depression Scale (HADS). Study Design: Cross sectional descriptive study. Place and Duration of Study: Out-patient department of Armed Forces Institute of Mental Health, Rawalpindi from June 2011 to December 2011. Methodology: Consecutive non probability sampling technique was used to select patients of age (25-70 years), male or female, who had received atleast 03 cycles of chemotherapy for solid tumors. Those with history of prior psychiatric illness, current use of psychotropic medication or psychoactive substance use, and any major bereavement in past one year were excluded from the study. After taking informed consent, relevant socio- demographic data was collected and HADS was administered. HADS-A cut off score of 7 was taken as significant anxiety while a HADS-D cut off score of 7 was taken as significant depression. Results: The total number of participants was 209. The mean age of patients was 42.9 years, with 55.5% males and 44.5% females. Overall 33/209 (15.8%) patients had anxiety while 56/209 (26.8%) were found to have depression. There was a higher frequency of anxiety and depression in younger patients (less than age 40 years), females, patients who were single or divorced, and patients receiving chemotherapy for pancreatic carcinoma. Conclusion: Patients undergoing chemotherapy suffer from considerable levels of anxiety and depression, thus highlighting the need for specialized interventions. (author)

Auger Electron Therapy And Brachytherapy Tumor Treatment

International Nuclear Information System (INIS)

Laster, B.H.; Shani, G.

2002-01-01

Auger Electron Therapy (AET) is a binary approach for improving cancer radiotherapy. It involves the selective targeting of an atom to tumor cells using physiological pathway. The atom is then irradiated by a specific radiation that produces secondary radiation called Auger electrons. One of the problems associated with the clinical application of AET, is that the energy of the photons required for stimulating photoelectric absorption in most of the available high Z target atoms, is too low to achieve penetration through normal surrounding tissues to the depth of the tumor, when an external source is used. The solution is therefore the use of a brachytherapy technique. There are two other problems associated with the use of radiation as a cancer treatment. The first is the limitation on radiation dose to the normal tissue within the treatment volume. The second problem is the limitation imposed by the miniscule size of the critical target of the cell, namely the DNA (0.25% of the cell mass). The solution to the first problem can be achieved by using the brachytherapy technique. The second problem can be resolved by placing the radiation source in close position to the DNA. AET, as we apply it, provides the two solutions to the two problems. When a photon is absorbed by an electron in the K or L shell of an high Z atom, the electron is ejected from the atom, creating a vacancy in the shell. This vacancy is immediately filled with an electron from an upper shell. The energy difference between the two shells is sometimes emitted as an x-ray, however, frequently the energy is transferred to an outer shell electron that is emitted as an Auger electron. These electrons are emitted at energies of up to ∼30 keV and therefore have a very short range in the cell. They will deposit all their energy within 20-30 nm from the point of emission. i.e. all the energy is deposited in the DNA. In our work indium is used as the high Z atom

Targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non thermal diode laser.

Science.gov (United States)

Ghannam, Magdy M; El Gebaly, Reem; Fadel, Maha

2016-04-05

The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. In this study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE encapsulated doxorubicin. The effect of lyophilization on liposomal stability and hence expiration date were studied. Moreover, the effect of diode laser on the drug released from liposomesin vitro and in vivo in mice carrying implanted solid tumor were also studied. The results indicated that lyophilization of the prepared liposomes encapsulating doxorubicin led to marked stability when stored at 5 °C and it is possible to use the re-hydrated lyophilized liposomes within 12 days post reconstitution. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells is a promising method in cancer therapy. We can conclude that lyophilization of the liposomes encapsulating doxorubicin lead to marked stability for the liposomes when stored at 5 °C. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells through the use of photosensitive sterically stabilized liposomes loaded with doxorubicin is a promising method. It proved to be applicable and successful for treatment of Ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin.

Proceedings of 11. Conference on Electron Microscopy of Solids

International Nuclear Information System (INIS)

2002-01-01

The conference is the cyclically organised discussion forum on problems connected with application of different electron microscopy techniques for the study of solid state materials. The main topics of 11 conference on Electron Microscopy of Solids held in Krynica (PL) in 2002 was: application of TEM in materials science; analytical techniques and orientation imaging in materials science; high resolution TEM in electronic materials; TEM and SEM application in ceramic and composites; advanced TEM techniques; advanced analytical and orientation imaging techniques; application of TEM in investigations of amorphous and nanocrystalline material; Intermetallic and superalloys; TEM application in martensite alloys; TEM and SEM application in research of iron base alloys; TEM studies of deformed alloys; TEM application in thin films and surface layer studies; TEM and SEM application in materials science

Proceedings of 10. Conference on Electron Microscopy of Solids

International Nuclear Information System (INIS)

1999-01-01

The new technical solutions and methodical variants of electron microscopy i. e. transmission electron microscopy and scanning electron microscopy have been presented. Development of new methods and microscope constructions which became more and more sophisticated causes the progress in possible applications. The broad spectrum of such applications in metallurgy, materials science, chemical engineering, electronics, physical chemistry, solid state physics, mineralogy and other branches of science and technique have been performed and discussed at the conference

Smart thermosensitive liposomes for effective solid tumor therapy and in vivo imaging.

Directory of Open Access Journals (Sweden)

Kevin Affram

Full Text Available In numerous studies, liposomes have been used to deliver anticancer drugs such as doxorubicin to local heat-triggered tumor. Here, we investigate: (i the ability of thermosensitive liposomal nanoparticle (TSLnp as a delivery system to deliver poorly membrane-permeable anticancer drug, gemcitabine (Gem to solid pancreatic tumor with the aid of local mild hyperthermia and, (ii the possibility of using gadolinium (Magnevist® loaded-TSLnps (Gd-TSLnps to increase magnetic resonance imaging (MRI contrast in solid tumor. In this study, we developed and tested gemcitabine-loaded thermosensitive liposomal nanoparticles (Gem-TSLnps and gadolinium-loaded thermosensitive liposomal nanoparticles (Gd-TSLnps both in in-vitro and in-vivo. The TSLnps exhibited temperature-dependent release of Gem, at 40-42°C, 65% of Gem was released within 10 min, whereas < 23% Gem leakage occurred at 37°C after a period of 2 h. The pharmacokinetic parameters and tissue distribution of both Gem-TSLnps and Gd-TSLnps were significantly greater compared with free Gem and Gd, while Gem-TSLnps plasma clearance was reduced by 17-fold and that of Gd-TSLpns was decreased by 2-fold. Area under the plasma concentration time curve (AUC of Gem-TSLnps (35.17± 0.04 μghr/mL was significantly higher than that of free Gem (2.09 ± 0.01 μghr/mL whereas, AUC of Gd-TSLnps was higher than free Gd by 3.9 fold high. TSLnps showed significant Gem accumulation in heated tumor relative to free Gem. Similar trend of increased Gd-TSLnps accumulation was observed in non-heated tumor compared to that of free Gd; however, no significant difference in MRI contrast enhancement between free Gd and Gd-TSLnps ex-vivo tumor images was observed. Despite Gem-TSLnps dose being half of free Gem dose, antitumor efficacy of Gem-TSLnps was comparable to that of free Gem(Gem-TSLnps 10 mg Gem/kg compared with free Gem 20 mg/kg. Overall, the findings suggest that TSLnps may be used to improve Gem delivery and enhance

New pbysical methods used in the study of composition, electronic properties and surface phenomena of solid substances. I. Electronic spectroscopies

International Nuclear Information System (INIS)

Toderean, A; Ilonca, Gh.

1981-01-01

The discovery of different kinds of interactions between solids and fotonic, respectively electronic and ionic beams, leads to the development of many new, very sensitive, physical methods for the study of solids. This monograph tries to present some of these methods, useful in compositional analysis, in the study of electronic properties and of the surface processes of solid substances. This is done from the point of view both of physical phenomena underlying them and of the information obtainable with such methods. But the whole monograph is limited only to the methods based on the electronic properties of the elements existing in the solid probes studied and this paper presents only those of them in which the detected beam is an electronic one, like: ELS, DAPS, ILS, AES, AEAPS, INS, TSS, XPS and UPS. (authors)

An overview of viral oncology in Italy - report from the Pavia meeting on solid tumors

Directory of Open Access Journals (Sweden)

Perfetti Vittorio

2012-09-01

Full Text Available Abstract This is a report on some of the research activities currently ongoing in Italy as outlined at the “Viruses and solid tumors” meeting jointly organized by the Oncology Sections of IRCCS Policlinico “San Matteo” (Pavia and IRCCS National Cancer Institute (Aviano, held in Pavia, Italy, on October 2011. Experts from the various disciplines involved in the study of the complex relationships between solid tumors and viruses met to discuss recent developments in the field and to report their personal contributions to the specified topics. Secondary end point was to establish a multidisciplinary work group specifically devoted to solid tumors and infectious agents, aimed to identify areas of common interest, promoting and establishing collaborative projects and programs, and to coordinate clinical and research activities. The group, which will be named IVOG (Italian Viral Oncology Group, will operate under the patronage of the various scientific societies of interest.

Total-dielectric-function approach to electron and phonon response in solids

International Nuclear Information System (INIS)

Penn, D.R.; Lewis, S.P.; Cohen, M.L.

1995-01-01

The interaction between two test charges, the response of a solid to an external field, and the normal modes of the solid can be determined from a total dielectric function that includes both electronic and lattice polarizabilities as well as local-field effects. In this paper we examine the relationship between superconductivity and the stability of a solid and derive sum rules for the electronic part of the dielectric function. It is also shown that there are negative eigenvalues of the total static dielectric function, implying the possibility of an attractive interaction between test charges. An attractive interaction is required for superconductivity

Molecular electronics with single molecules in solid-state devices

DEFF Research Database (Denmark)

Moth-Poulsen, Kasper; Bjørnholm, Thomas

2009-01-01

The ultimate aim of molecular electronics is to understand and master single-molecule devices. Based on the latest results on electron transport in single molecules in solid-state devices, we focus here on new insights into the influence of metal electrodes on the energy spectrum of the molecule...

In Vivo Monitoring of pH, Redox Status, and Glutathione Using L-Band EPR for Assessment of Therapeutic Effectiveness in Solid Tumors

Science.gov (United States)

Bobko, Andrey A.; Eubank, Timothy D.; Voorhees, Jeffrey L.; Efimova, Olga V.; Kirilyuk, Igor A.; Petryakov, Sergey; Trofimiov, Dmitrii G.; Marsh, Clay B.; Zweier, Jay L.; Grigor’ev, Igor A.; Samouilov, Alexandre; Khramtsov, Valery V.

2011-01-01

Approach for in vivo real-time assessment of tumor tissue extracellular pH (pHe), redox, and intracellular glutathione based on L-band EPR spectroscopy using dual function pH and redox nitroxide probe and disulfide nitroxide biradical, is described. These parameters were monitored in PyMT mice bearing breast cancer tumors during treatment with granulocyte macrophage colony-stimulating factor. It was observed that tumor pHe is about 0.4 pH units lower than that in normal mammary gland tissue. Treatment with granulocyte macrophage colony-stimulating factor decreased the value of pHe by 0.3 units compared with PBS control treatment. Tumor tissue reducing capacity and intracellular glutathione were elevated compared with normal mammary gland tissue. Granulocyte macrophage colony-stimulating factor treatment resulted in a decrease of the tumor tissue reducing capacity and intracellular glutathione content. In addition to spectroscopic studies, pHe mapping was performed using recently proposed variable frequency proton–electron double-resonance imaging. The pH mapping superimposed with MRI image supports probe localization in mammary gland/tumor tissue, shows high heterogeneity of tumor tissue pHe and a difference of about 0.4 pH units between average pHe values in tumor and normal mammary gland. In summary, the developed multifunctional approach allows for in vivo, noninvasive pHe, extracellular redox, and intracellular glutathione content monitoring during investigation of various therapeutic strategies for solid tumors. Magn Reson Med 000:000–000, 2011. PMID:22113626

MRI after magnetic drug targeting in patients with advanced solid malignant tumors

International Nuclear Information System (INIS)

Lemke, A.-J.; Senfft von Pilsach, M.-I.; Felix, R.; Luebbe, A.; Bergemann, C.; Riess, H.

2004-01-01

The purpose of this study was to evaluate the ability of MRI to detect magnetic particle uptake into advanced solid malignant tumors and to document the extension of these tumors, carried out in the context of magnetic drug targeting. In a prospective phase I trial, 11 patients were examined with MRI before and after magnetic drug targeting. The sequence protocol included T1-WI and T2-WI in several planes, followed by quantitative and qualitative evaluation of the signal intensities and tumor extensions. In nine patients, a signal decrease was observed in the early follow-up (2-7 days after therapy) on the T2-weighted images; two patients did not show a signal change. The signal changes in T1-WI were less distinct. In late follow-up (4-6 weeks after therapy), signal within nine tumors reached their initially normal level on both T1-WI and T2-WI; two tumors showed a slight signal decrease on T2-WI and a slight signal increase on T1-WI. Within the surveillance period, tumor remission in 3 out of 11 patients was observed, and in 5 patients tumor growth had stopped. The remaining three patients showed significant tumor growth. There was no statistically significant correlation between signal change and response. MRI is a suitable method to detect magnetite particles, deposited at the tumor site via magnetic drug targeting. MRI is therefore eligible to control the success of MDT and to assess the tumor size after the end of therapy. (orig.)

In vitro anti-proliferative effect of interferon alpha in solid tumors: A potential predicative test

International Nuclear Information System (INIS)

Fuchsberger, N.; Kubes, M.; Kontsek, P.; Borecky, L.; Hornak, M.; Silvanova; Godal, A.; Svec, J.

1993-01-01

An in vitro test for the anti-proliferative effect of human leukocyte interferon (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32 patients with either malignant melanoma (13), renal carcinoma (4) or bladder carcinoma (15). Our results demonstrated activity of IFN in all three groups of solid tumors. However, appreciable differences in sensitivity to anti-proliferative effect of IFN between individual tumors of the same type were found. The potential of this anti-proliferative test for prediction of treatment response in IFN-therapy is discussed. (author)

Whole-body magnetic resonance imaging for detection of skeletal metastases in children and young people with primary solid tumors - systematic review

International Nuclear Information System (INIS)

Smets, A.M.; Deurloo, E.E.; Slager, T.J.E.; Stoker, J.; Bipat, S.

2018-01-01

Many solid neoplasms have a propensity for osteomedullary metastases of which detection is important for staging and subsequent treatment. Whole-body magnetic resonance imaging (WB-MRI) has been shown to accurately detect osteomedullary metastases in adults, but these findings cannot be unconditionally extrapolated to staging of children with malignant solid tumors. To conduct a literature review on the sensitivity of WB-MRI for detecting skeletal metastases in children with solid tumors. Searches in MEDLINE and EMBASE databases up to 15 May 2017 were performed to identify studies on the diagnostic value of WB-MRI. Inclusion criteria were children and adolescents (age <21 years) with a primary solid tumor who were evaluated for skeletal metastases by WB-MRI and compared to any type of reference standard. The number of included patients had to be at least five and data on true positives, true negatives, false-positives and false-negatives had to be extractable. Five studies including 132 patients (96 patients with solid tumors) were eligible. Patient groups and used reference tests were heterogeneous, producing unclear or high risk of bias. Sensitivity of WB-MRI ranged between 82% and 100%. The positive predictive value of WB-MRI was variable among the studies and influenced by the used reference standard. Although WB-MRI may seem a promising radiation-free technique for the detection of skeletal metastases in children with solid tumors, published studies are small and too heterogeneous to provide conclusive evidence that WB-MRI can be an alternative to currently used imaging techniques. (orig.)

Whole-body magnetic resonance imaging for detection of skeletal metastases in children and young people with primary solid tumors - systematic review

Energy Technology Data Exchange (ETDEWEB)

Smets, A.M.; Deurloo, E.E.; Slager, T.J.E.; Stoker, J.; Bipat, S. [Academic Medical Center (AMC), Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands)

2018-02-15

Many solid neoplasms have a propensity for osteomedullary metastases of which detection is important for staging and subsequent treatment. Whole-body magnetic resonance imaging (WB-MRI) has been shown to accurately detect osteomedullary metastases in adults, but these findings cannot be unconditionally extrapolated to staging of children with malignant solid tumors. To conduct a literature review on the sensitivity of WB-MRI for detecting skeletal metastases in children with solid tumors. Searches in MEDLINE and EMBASE databases up to 15 May 2017 were performed to identify studies on the diagnostic value of WB-MRI. Inclusion criteria were children and adolescents (age <21 years) with a primary solid tumor who were evaluated for skeletal metastases by WB-MRI and compared to any type of reference standard. The number of included patients had to be at least five and data on true positives, true negatives, false-positives and false-negatives had to be extractable. Five studies including 132 patients (96 patients with solid tumors) were eligible. Patient groups and used reference tests were heterogeneous, producing unclear or high risk of bias. Sensitivity of WB-MRI ranged between 82% and 100%. The positive predictive value of WB-MRI was variable among the studies and influenced by the used reference standard. Although WB-MRI may seem a promising radiation-free technique for the detection of skeletal metastases in children with solid tumors, published studies are small and too heterogeneous to provide conclusive evidence that WB-MRI can be an alternative to currently used imaging techniques. (orig.)

Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

Science.gov (United States)

Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

2003-07-15

Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

Ultrasonic enhancement of drug penetration in solid tumors

Directory of Open Access Journals (Sweden)

Chun-yen eLai

2013-08-01

Full Text Available Increasing the penetration of drugs within solid tumors can be accomplished through multiple ultrasound-mediated mechanisms. The application of ultrasound can directly change the structure or physiology of tissues or can induce changes in a drug or vehicle in order to enhance delivery and efficacy. With each ultrasonic pulse, a fraction of the energy in the propagating wave is absorbed by tissue and results in local heating. When ultrasound is applied to achieve mild hyperthermia, the thermal effects are associated with an increase in perfusion or the release of a drug from a temperature-sensitive vehicle. Higher ultrasound intensities locally ablate tissue and result in increased drug accumulation surrounding the ablated region of interest. Further, the mechanical displacement induced by the ultrasound pulse can result in the nucleation, growth and collapse of gas bubbles. As a result of such cavitation, the permeability of a vessel wall or cell membrane can be increased. Finally, the radiation pressure of the propagating pulse can translate particles or tissues. In this perspective, we will review recent progress in ultrasound-mediated tumor delivery and the opportunities for clinical translation.

Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

Science.gov (United States)

Soltani, M; Chen, P

2013-01-01

Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

Directory of Open Access Journals (Sweden)

M Soltani

Full Text Available Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

Energy Technology Data Exchange (ETDEWEB)

Schaffner, Florence; Ray, Anne Marie; Dontenwill, Monique, E-mail: monique.dontenwill@unistra.fr [UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral signaling and therapeutic targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch (France)

2013-01-15

Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

Antibody or Antibody Fragments : Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

NARCIS (Netherlands)

Xenaki, Katerina T; Oliveira, Sabrina; van Bergen En Henegouwen, Paul M P

2017-01-01

The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody-drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are

CD 99 immunocytochemistry in solid pseudopapillary tumor of pancreas: A study on fine-needle aspiration cytology smears.

Science.gov (United States)

Ghosh, Ranajoy; Mallik, Saumya R; Mathur, Sandeep R; Iyer, Venkateswaran K

2013-07-01

Solid pseudopapillary tumor of pancreas (SPTP) is a rare pancreatic tumor of uncertain histogenesis usually affecting young women. Though these tumors have characteristic cytomorphology, it is sometimes difficult to differentiate them from neuroendocrine tumors of the pancreas. We reviewed cases of SPTP to delineate the diagnostic cytological features and also observed utility of CD 99 (MIC 2) immunostaining to aid in the diagnosis of this tumor. This study was designed to demonstrate the utility of CD 99 immunostaining along with cytological features for making a pre-operative diagnosis and delineating it from the neuroendocrine tumor of pancreas which is a close mimic. Cytomorphological features of 11 cases of solid pseudopapillary neoplasm diagnosed by pre-operative fine-needle aspiration cytology (FNAC) at our institute were reviewed. Immunocytochemistry for CD 99 was also performed on the smears. All the cases had cellular smears with monomorphic cells lying singly, as loosely cohesive clusters as well as forming delicate pseudopapillae. Presence of intra and extra-cellular basement membrane material, background foamy macrophages and nuclear grooves were the other salient features. Immunocytochemistry for CD 99 could be performed on eight cases and demonstrated typical paranuclear dot-like positivity. Pre-operative early diagnosis of SPTP can be made by FNAC which can further be aided by CD 99 immunocytochemistry.

Molecular electronics with single molecules in solid-state devices.

Science.gov (United States)

Moth-Poulsen, Kasper; Bjørnholm, Thomas

2009-09-01

The ultimate aim of molecular electronics is to understand and master single-molecule devices. Based on the latest results on electron transport in single molecules in solid-state devices, we focus here on new insights into the influence of metal electrodes on the energy spectrum of the molecule, and on how the electron transport properties of the molecule depend on the strength of the electronic coupling between it and the electrodes. A variety of phenomena are observed depending on whether this coupling is weak, intermediate or strong.

Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.

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Lambert, John M; Morris, Charles Q

2017-05-01

Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment.

Comparison of F-18-FDG PET/CT findings between pancreatic solid pseudopapillary tumor and pancreatic ductal adenocarcinoma

International Nuclear Information System (INIS)

Kim, Yong-il; Kim, Seok-ki; Paeng, Jin Chul; Lee, Ho-Young

2014-01-01

Objective: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor. Little data are available on positron emission tomographic/computed tomographic (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic characteristics of SPT using F-18-FDG PET/CT and compared the results with those of pancreatic ductal adenocarcinoma. Methods: We retrospectively reviewed the records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT patients had primary tumors and 1 patient had metastatic SPT. Maximum standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were evaluated. Mann–Whitney U test between pancreatic SPT and ductal adenocarcinoma was performed. In addition, age, gender and tumor size-adjusted analysis of covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma. Results: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and after PET/CT had suggested the presence of pancreatic SPT. Conclusion: We recommend that SPT be considered when a solid pancreatic mass with increased FDG metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting subtle metastases of SPT

Backscattering of projectile-bound electrons from solid surfaces

International Nuclear Information System (INIS)

Tobisch, M.; Schosnig, M.; Kroneberger, K.; Kuzel, M.; Maier, R.; Jung, M.; Fiedler, C.; Rothard, H.; Clouvas, A.; Suarez, S.; Groeneveld, K.O.

1994-01-01

The contribution of projectile ionization (PI) to secondary electron emission is studied by collision of H 2 + and H 3 + ions (400 keV/u and 700 keV/u) with carbon, copper and gold targets (600 A). The measured doubly differential intensity distribution shows a peak of lost projectile electrons near - v p . We describe the subtraction of the contribution of target ionization (TI), and compare the remaining electron intensities with a BEA calculation. For solids we observe a strong energy shift of the electron loss peak, which is compared with the influence of electron transport and binding energy. Furthermore, the low energy tail of the electron loss peak indicates the simultaneous occurrence of PI and TI. Finally we discuss the influence of surface conditions and the dependence of the observation angles on the measured electron intensities. (orig.)

Bifidobacterial recombinant thymidine kinase-ganciclovir gene therapy system induces FasL and TNFR2 mediated antitumor apoptosis in solid tumors

International Nuclear Information System (INIS)

Wang, Changdong; Ma, Yongping; Hu, Qiongwen; Xie, Tingting; Wu, Jiayan; Zeng, Fan; Song, Fangzhou

2016-01-01

Directly targeting therapeutic suicide gene to a solid tumor is a hopeful approach for cancer gene therapy. Treatment of a solid tumor by an effective vector for a suicide gene remains a challenge. Given the lack of effective treatments, we constructed a bifidobacterial recombinant thymidine kinase (BF-rTK) -ganciclovir (GCV) targeting system (BKV) to meet this requirement and to explore antitumor mechanisms. Bifidobacterium (BF) or BF-rTK was injected intratumorally with or without ganciclovir in a human colo320 intestinal xenograft tumor model. The tumor tissues were analyzed using apoptosis antibody arrays, real time PCR and western blot. The colo320 cell was analyzed by the gene silencing method. Autophagy and necroptosis were also detected in colo320 cell. Meanwhile, three human digestive system xenograft tumor models (colorectal cancer colo320, gastric cancer MKN-45 and liver cancer SSMC-7721) and a breast cancer (MDA-MB-231) model were employed to validate the universality of BF-rTK + GCV in solid tumor gene therapy. The survival rate was evaluated in three human cancer models after the BF-rTK + GCV intratumor treatment. The analysis of inflammatory markers (TNF-α) in tumor indicated that BF-rTK + GCV significantly inhibited TNF-α expression. The results suggested that BF-rTK + GCV induced tumor apoptosis without autophagy and necroptosis occurrence. The apoptosis was transduced by multiple signaling pathways mediated by FasL and TNFR2 and mainly activated the mitochondrial control of apoptosis via Bid and Bim, which was rescued by silencing Bid or/and Bim. However, BF + GCV only induced apoptosis via Fas/FasL signal pathway accompanied with increased P53 expression. We further found that BF-rTK + GCV inhibited the expression of the inflammatory maker of TNF-α. However, BF-rTK + GCV did not result in necroptosis and autophagy. BF-rTK + GCV induced tumor apoptosis mediated by FasL and TNFR2 through the mitochondrial control of apoptosis via Bid and Bim

FLAG-tagged CD19-specific CAR-T cells eliminate CD19-bearing solid tumor cells in vitro and in vivo.

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Berahovich, Robert; Xu, Shirley; Zhou, Hua; Harto, Hizkia; Xu, Qumiao; Garcia, Andres; Liu, Fenyong; Golubovskaya, Vita M; Wu, Lijun

2017-06-01

Autologous T cells expressing chimeric antigen receptors (CARs) specific for CD19 have demonstrated remarkable efficacy as therapeutics for B cell malignancies. In the present study, we generated FLAG-tagged CD19-specific CAR-T cells (CD19-FLAG) and compared them to their non-tagged counterparts for their effects on solid and hematological cancer cells in vitro and in vivo . For solid tumors, we used HeLa cervical carcinoma cells engineered to overexpress CD19 (HeLa-CD19), and for hematological cancer we used Raji Burkitt's lymphoma cells, which endogenously express CD19. Like non-tagged CD19 CAR-T cells, CD19-FLAG CAR-T cells expanded in culture >100-fold and exhibited potent cytolytic activity against both HeLa-CD19 and Raji cells in vitro . CD19-FLAG CAR-T cells also secreted significantly more IFN-gamma and IL-2 than the control T cells. In vivo , CD19-FLAG CAR-T cells significantly blocked the growth of HeLa-CD19 solid tumors, increased tumor cleaved caspase-3 levels, and expanded systemically. CD19-FLAG CAR-T cells also significantly reduced Raji tumor burden and extended mouse survival. These results demonstrate the strong efficacy of FLAG-tagged CD19 CAR-T cells in solid and hematological cancer models.

Applications of lipid nanocarriers for solid tumors therapy: literature review

International Nuclear Information System (INIS)

Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury; Taveira, Eliseu Jose Fleury

2012-01-01

Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed R database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

The combined effect of interferon synthesis inductors, radiosensitizing and antitumoral agents on solid tumors

International Nuclear Information System (INIS)

Leonidze, D.L.

1987-01-01

In experiments with mice bearing solid sarcoma 37 a study was conducted on the combined effect of radiation and inductors of endogenous inerferon synthesis (IEIS), together with hyperthermia or together with an alkylating and carbomoilating agent, dimethinur. The effect was estimated by the tumor growth coefficient and by the number of animals with the regressed tumors. Poly I; polyC was not shiown to influence the efficiency of hyperthermia combined with radiation with radiation; dextransulphate and tiloron increased the radiosensitizing effect of hyperthermia. Dimethinur aggravated the effect of radiation, but with IEIS used together with dimethynur and radiation, the response of the tumor increased insignificantly as compared to the effect of IEIS together with radiation

Principles of electron backscattering by solids and thin films

International Nuclear Information System (INIS)

Niedrig, H.

1977-01-01

The parameters concerning the electron backscattering from thin films and solids (atomic scattering cross-section, atomic number, single/multiple scattering, film thickness of self-supporting films and of surface films on bulk substrates, scattering angular distribution, angle of incidence, diffraction effects) are described. Their influence on some important contrast mechanisms in scanning electron microscopy (thickness contrast, Z/material contrast, tilting/topography contrast, orientation contrast) is discussed. The main backscattering electron detection systems are briefly described. (orig.) [de

Cancer stem cells in solid tumors: is 'evading apoptosis' a hallmark of cancer?

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Enderling, Heiko; Hahnfeldt, Philip

2011-08-01

Conventional wisdom has long held that once a cancer cell has developed it will inevitably progress to clinical disease. Updating this paradigm, it has more recently become apparent that the tumor interacts with its microenvironment and that some environmental bottlenecks, such as the angiogenic switch, must be overcome for the tumor to progress. In parallel, attraction has been drawn to the concept that there is a minority population of cells - the cancer stem cells - bestowed with the exclusive ability to self-renew and regenerate the tumor. With therapeutic targeting issues at stake, much attention has shifted to the identification of cancer stem cells, the thinking being that the remaining non-stem population, already fated to die, will play a negligible role in tumor development. In fact, the newly appreciated importance of intercellular interactions in cancer development also extends in a unique and unexpected way to interactions between the stem and non-stem compartments of the tumor. Here we discuss recent findings drawn from a hybrid mathematical-cellular automaton model that simulates growth of a heterogeneous solid tumor comprised of cancer stem cells and non-stem cancer cells. The model shows how the introduction of cell fate heterogeneity paradoxically influences the tumor growth dynamic in response to apoptosis, to reveal yet another bottleneck to tumor progression potentially exploitable for disease control. Copyright © 2011 Elsevier Ltd. All rights reserved.

Differential cross sections for elastic scattering of electrons by atoms and solids

International Nuclear Information System (INIS)

Jablonski, A.; Salvat, F.; Powell, C.J.

2004-01-01

Differential cross sections (DCSs) for elastic scattering of electrons by neutral atoms are extensively used in studies of electron transport in solids and liquids. A new NIST database has recently been released with DCSs calculated from a relativistic Dirac partial-wave analysis in which the potentials were obtained from Dirac-Hartree-Fock electron densities computed self-consistently for free atoms. We have compared calculated DCSs with measured DCSs for argon for electron energies between 50 eV and 3 keV, and found good agreement for electron energies above about 1 keV but with increasing deviations as the energy is reduced. These deviations are due to the neglect of absorption and polarizability effects in the calculations. Nevertheless, DCSs for neutral atoms have been successfully used in simulations of elastic backscattering of electrons by solid surfaces with energies down to 300 eV as well as for many other applications. It is suggested that this success might be due at least partially to the smaller absorption correction for the DCSs in solids on account of the smaller total inelastic scattering cross sections than for the corresponding free atoms

Electron stimulated reactions of methyl iodide coadsorbed with amorphous solid water

International Nuclear Information System (INIS)

Perry, C. C.; Faradzhev, N. S.; Madey, T. E.; Fairbrother, D. H.

2007-01-01

The electron stimulated reactions of methyl iodide (MeI) adsorbed on and suspended within amorphous solid water (ice) were studied using a combination of postirradiation temperature programmed desorption and reflection absorption infrared spectroscopy. For MeI adsorbed on top of amorphous solid water (ice), electron beam irradiation is responsible for both structural and chemical transformations within the overlayer. Electron stimulated reactions of MeI result principally in the formation of methyl radicals and solvated iodide anions. The cross section for electron stimulated decomposition of MeI is comparable to the gas phase value and is only weakly dependent upon the local environment. For both adsorbed MeI and suspended MeI, reactions of methyl radicals within MeI clusters lead to the formation of ethane, ethyl iodide, and diiodomethane. In contrast, reactions between the products of methyl iodide and water dissociation are responsible for the formation of methanol and carbon dioxide. Methane, formed as a result of reactions between methyl radicals and either parent MeI molecules or hydrogen atoms, is also observed. The product distribution is found to depend on the film's initial chemical composition as well as the electron fluence. Results from this study highlight the similarities in the carbon-containing products formed when monohalomethanes coadsorbed with amorphous solid water are irradiated by either electrons or photons

Scanning electron microscopic studies on bone tumors

International Nuclear Information System (INIS)

Itoh, Motoya

1978-01-01

Surface morphological observations of benign and malinant bone tumors were made by the use of scanning electron microscopy. Tumor materials were obtained directly from patients of osteogenic sarcomas, chondrosarcomas, enchondromas, giant cell tumors and Paget's sarcoma. To compare with these human tumors, the following experimental materials were also observed: P 32 -induced rat osteogenic sarcomas with their pulmonary metastatic lesions, Sr 89 -induced transplantable mouse osteogenic sarcomas and osteoid tissues arising after artificial fractures in mice. One of the most outstanding findings was a lot of granular substances seen on cell surfaces and their intercellular spaces in osteoid or chondroid forming tissues. These substances were considered to do some parts in collaborating extracellular matrix formation. Protrusions on cell surface, such as mucrovilli were more or less fashioned by these granular substances. Additional experiments revealed these substances to be soluble in sodium cloride solution. Benign osteoid forming cells, such as osteoblasts and osteoblastic osteosarcoma cells had granular substances on their surfaces and their intercellular spaces. On the other hand, undifferentiated transplantable osteosarcoma which formed on osteoid or chondroid matrix had none of these granular substances. Consequently, the difference of surface morphology between osteosarcoma cells and osteoblasts was yet to be especially concluded. (author)

Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.

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Heba Bassiony

Full Text Available BACKGROUND: Magnetite nanoparticles (MNPs have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues. METHOD: MNPs coated with ascorbic acid (size: 25.0±5.0 nm were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT or intraperitoneally (IP. Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry. RESULTS: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group. CONCLUSION: MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-cell Engager.

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Wing, Anna; Fajardo, Carlos Alberto; Posey, Avery D; Shaw, Carolyn; Da, Tong; Young, Regina M; Alemany, Ramon; June, Carl H; Guedan, Sonia

2018-05-01

T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors. We report that CART cells targeting the folate receptor alpha (FR-α) successfully infiltrated preestablished xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. We demonstrated that OAd-BiTE-mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells redirected CART cells toward EGFR in the absence of FR-α, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells. The combinatorial approach improved antitumor efficacy and prolonged survival in mouse models of cancer when compared with the monotherapies, and this was the result of an increased BiTE-mediated T-cell activation in tumors. Overall, these results demonstrated that the combination of a BiTE-expressing oncolytic virus with adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as monotherapies in solid tumors and encourage its further evaluation in human trials. Cancer Immunol Res; 6(5); 605-16. ©2018 AACR . ©2018 American Association for Cancer Research.

Monoclonal antibodies and Fc fragments for treating solid tumors

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Eisenbeis AM

2012-01-01

Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

Imaging of solid tumor using near-infrared emitting purple bacteria

International Nuclear Information System (INIS)

Moon, Sung Min; Min, Jung Joon; Kim, Sun A; Choy, Hyon E.; Bom, Hee Seung

2005-01-01

Rhodobacter sphaeroides 2.4.1 is α-3 purple nonsulfur eubacterium with an extensive metabolism. Under anaerobic conditions, it is able to grow by photosynthesis, respiration and fermentation. When grown photosynthetically, it uses wavelengths of light in the near-infrared and contains a reaction center that is the peripheral light-harvesting (LH2) complex. These molecules absorb and emit near-infrared light. Using this near-infrared fluorescent bacterial we investigated its targeting capacity of solid tumor in small animals. R. sphaeroides 2.4.1 strains were cultured in sistrons minimal medium A (SIS) at 32 C. Xenograft tumor model has been established by subcutaneous injection of CT26 mouse colon cancer cell line. 1X10 8 Rhodobacter sphaeroides cells suspended in 100 ul of PBS were injected via tail vein with 1-cc insulin syringe into tumor bearing mouse. In vivo fluorescence imaging has been done after 20 min to 30 days of purple bacteria using indocyanine (ICG) emission filter (Em=810∼835 nm). Near-infrared imaging signal from Rhodobacter sphaeroides was initially detected at liver for 3 days but at the necrotic region of tumor mass thereafter. Total photon flux measured 5.5X10 8 (p/s/cm 2 /sr) at Day 1. Also it was increased to 7.8X10 8 (p/s/cm 2 /sr) at 12 day. One of important characteristic is that the signal appeared only at central necrosis area. It has been monitored for 36 day. We successfully imaged cancer with near-infrared fluorescence bacteria. Our result indicate that near-infrared fluorescence purple bacteria are able to be used to monitor bacterial trafficking in living tumor models

Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

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Millard M

2017-10-01

Full Text Available Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France; 3Laboratory of Biophysics and Biotechnology, 4International Sakharov Environmental Institute, Belarusian State University, Minsk, Belarus; 5Department of Radiology, Medical Company Sunkar, Almaty, Kazakhstan Abstract: The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a

Thermal characterization of indirectly heated axi-symmetric solid cathode electron beam gun for melting application

International Nuclear Information System (INIS)

Prakash, B.; Gupta, S.; Malik, P.; Mishra, K.K.; Jha, M.N.; Kandaswamy, E.; Martin, M.

2015-01-01

Electron beam melting gun with indirectly heated axi-symmetric solid cathode was designed, fabricated and characterized experimentally. The thermal simulation and optical analysis of the electron gun was carried out to estimate the power required to achieve the emission temperature of the solid cathode, to obtain the temperature distribution in the assembly and the beam transportation. On the basis of the thermal simulation and electron optics, the electron gun design was finalised. The electron gun assembly was fabricated and installed in the vacuum chamber for carrying out the experiment to find the actual temperature distribution. Thermocouple and two colour pyrometer were used to measure the temperature at various locations in the electron gun. The attenuation effect of the viewing port glass of the vacuum chamber was compensated in the final reading of the temperature measured by the pyrometer. The temperature of solid cathode obtained by the experiment was found to be 2800K which is the emission temperature of solid cathode. (author)

Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors.

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Danika Lindsay

2016-08-01

Full Text Available Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the

Electronic structure and optical properties of solid C60

International Nuclear Information System (INIS)

Mattesini, M.; Ahuja, R.; Sa, L.; Hugosson, H.W.; Johansson, B.; Eriksson, O.

2009-01-01

The electronic structure and the optical properties of face-centered-cubic C 60 have been investigated by using an all-electron full-potential method. Our ab initio results show that the imaginary dielectric function for high-energy values looks very similar to that of graphite, revealing close electronic structure similarities between the two systems. We have also identified the origin of different peaks in the dielectric function of fullerene by means of the calculated electronic density of states. The computed optical spectrum compares fairly well with the available experimental data for the Vis-UV absorption spectrum of solid C 60 .

A correlative optical microscopy and scanning electron microscopy approach to locating nanoparticles in brain tumors.

Science.gov (United States)

Kempen, Paul J; Kircher, Moritz F; de la Zerda, Adam; Zavaleta, Cristina L; Jokerst, Jesse V; Mellinghoff, Ingo K; Gambhir, Sanjiv S; Sinclair, Robert

2015-01-01

The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Secondary solid tumors following radiation in Hodgkin's disease: experience of the Institut Gustave-Roussy

International Nuclear Information System (INIS)

Cosset, J.M.; Henry-Amar, M.; Dietrich, P.Y.; Socie, G.; Girinsky, T.; Hayat, M.; Tubiana, M.

1992-01-01

From 1961 to 1984, in the Institut Gustave-Roussy, 893 patients have been treated in Hodgkin's disease. The authors study the solid tumors that they have observed after exclusive radiotherapy and chemo-radiotherapy in order to know the radiation effect in the birth of this type of cancer

Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

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Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

2015-01-01

Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

Echinococcus cysticus of the liver - sonographic pattern suggestive of solid tumor

International Nuclear Information System (INIS)

Grosser, G.; Hauenstein, K.H.; Henke, W.

1985-01-01

In a patient with Hodgkin's disease, an intrahepatic echodense mass was diagnosed incidentally by ultrasonography. The sonographic pattern suggested a solid tumor. Despite negative or borderline serology, computed tomography establised the diagnosis of echinococcus cysticus by documentation of one ''daughter'' cyst; this diagnosis was confirmed by surgery. The criteria of echinococcus cysticus in modern imaging methods like sonography and computed tomography are summarized and the diagnostic value of various procedures including diagnostic procedure in seronegative cases are discussed. (orig.) [de

Relation of radiation damage of metallic solids to electronic structure. Pt. 5

International Nuclear Information System (INIS)

Shalaev, A.M.; Adamenko, A.A.

1977-01-01

The problem of relating a damage in metal solids to the parameters of radiation fluxes and the physical nature of a target is considered. Basing upon experimental and theoretical investigations into the processes of interaction of particle fluxes with solids, the following conclusions have been reached. Threshold energy of ion displacement in the crystal lattice of a metal solid is dependent on the energy of a bombarding particle, which is due to ionization and electroexcitation stimulated by energy transfer from a fast particle to a system of collectivized electrons. The rate of metal solid damage by radiation depends on the state of the crystal lattice, in particular on its defectness. Variations of local electron density in the vicinity of a defect are related with changing thermodynamic characteristics of radiation-induced defect formation. A type of atomic bond in a solid affects the rate of radiation damage. The greatest damage occurs in materials with a covalent bond

Electron holography for fields in solids: problems and progress.

Science.gov (United States)

Lichte, Hannes; Börrnert, Felix; Lenk, Andreas; Lubk, Axel; Röder, Falk; Sickmann, Jan; Sturm, Sebastian; Vogel, Karin; Wolf, Daniel

2013-11-01

Electron holography initially was invented by Dennis Gabor for solving the problems raised by the aberrations of electron lenses in Transmission Electron Microscopy. Nowadays, after hardware correction of aberrations allows true atomic resolution of the structure, for comprehensive understanding of solids, determination of electric and magnetic nanofields is the most challenging task. Since fields are phase objects in the TEM, electron holography is the unrivaled method of choice. After more than 40 years of experimental realization and steady improvement, holography is increasingly contributing to these highly sophisticated and essential questions in materials science, as well to the understanding of electron waves and their interaction with matter. © 2013 Elsevier B.V. All rights reserved.

Electron momentum spectroscopy of solids by the (e,2e) reaction

International Nuclear Information System (INIS)

Kheifets, A.S.; Vos, M.; Canney, S.A.; Guo, X.; McCarthy, I.E.

1996-08-01

Recent developments in (e,2e) momentum spectroscopy have resulted in the study of a diverse range of solid targets. These studies have revealed the electronic structure of solids in much more detail that was previously available using this technique. The method is now capable of producing quantitative data on energy-resolved momentum density of solids. A summary of these results is presented, in particular for aluminium, aluminium oxides and graphite. 26 refs., 9 figs

Geminate electron--cation recombination in disordered solids

International Nuclear Information System (INIS)

Berlin, Y.A.; Chekunaev, N.I.; Goldanskii, V.I.

1990-01-01

A theory of a geminate electron--cation recombination has been developed using the percolation approach to the description of the electron transport in disordered solids. Following this approach all trapping sites are separated into two groups. The first group forms a diffusion cluster responsible for the macroscopic charge transfer in disordered media whilethe second group consists of isolated traps playing the role of origins and sinks for mobile electrons. In the framework of such a model an equation has been derived describing the electron motion in the Coulomb field of a parent cation. The solution of this equation in the long time limit shows that the recombination rate decreases vs time as t -(1+α/2) with α being a positive constant or a very weak function of t. In the particular case of Gaussian diffusion α=1 and the kinetic law obtained reduces to that predicted by the well-known Onsager--Smoluchowski theory. However for the dispersive (non-Gaussian) transport in highly disordered systems α<1 and its value depends on the type of disorder, on the energy level structure of trapped electrons and on the specific mechanism of electron migration through the medium

Proton stoichiometry of electron transport in rodent tumor mitoplasts.

Science.gov (United States)

Ferreira, J; Reynafarje, B; Costa, L E; Lehninger, A L

1988-02-01

The mechanistic vectorial H+/O translocation ratios characteristic of energy-conserving sites 2 + 3 and site 3 of the respiratory chain of two tumor cell lines were determined using succinate and ferrocytochrome c, respectively, as electron donors. The measurements were carried out on mitoplasts in order to allow ferrocytochrome c free access to its binding site on the inner mitochondrial membrane. The tumor cell lines used were Ehrlich ascites tumor and the AS30-D ascites tumor. K+ was used as charge-compensating cation in the presence of valinomycin. The O2 uptake rate measurements were made with a fast-responding membrane-less electrode whose response time was closely matched with that of a pH electrode. The rates of O2 uptake and H+ ejection during the apparent zero-order rate phase of respiration, analyzed by computer, were extrapolated to zero time. The observed H+/O ratios for succinate oxidation in both tumors exceeded 7 and approached 8 and the H+/O ratios for the cytochrome oxidase reaction closely approached 4.0, in agreement with data or normal mitochondria. However, the rates of H+ back decay in the tumor mitochondria are relatively high and may influence the net efficiency of oxidative phosphorylation under intracellular conditions.

Echinococcus cysticus of the liver - sonographic pattern suggestive of solid tumor

Energy Technology Data Exchange (ETDEWEB)

Grosser, G.; Hauenstein, K.H.; Henke, W.

1985-09-01

In a patient with Hodgkin's disease, an intrahepatic echodense mass was diagnosed incidentally by ultrasonography. The sonographic pattern suggested a solid tumor. Despite negative or borderline serology, computed tomography establised the diagnosis of echinococcus cysticus by documentation of one ''daughter'' cyst; this diagnosis was confirmed by surgery. The criteria of echinococcus cysticus in modern imaging methods like sonography and computed tomography are summarized and the diagnostic value of various procedures including diagnostic procedure in seronegative cases are discussed.

Monitoring the effect of belinostat in solid tumors by H4 acetylation

DEFF Research Database (Denmark)

Marquard, L.; Petersen, K.D.; Persson, M.

2008-01-01

after treatment with HDAC inhibitors, and could thus be used as a marker for monitoring cellular response to HDAC inhibitor treatment. Here we describe the utility of a newly described monoclonal antibody against acetylated H4 for immunohistochemistry on paraffin-embedded fine needle biopsies from nude...... acetylation in fine needle biopsies using the T25 antibody may prove useful in monitoring HDAC inhibitor efficacy in clinical trials involving humans with solid tumors Udgivelsesdato: 2008/5...

Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

Science.gov (United States)

de Paula Silva, Neimar; de Souza Reis, Rejane; Garcia Cunha, Rafael; Pinto Oliveira, Júlio Fernando; Santos, Marceli de Oliveira; Pombo-de-Oliveira, Maria S; de Camargo, Beatriz

2016-01-01

Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics. A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma). Children aged birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS) was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01)). Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma. This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

Solid tumor models for the assessment of different treatment modalities. XIV. The evaluation of host and tumor response to cyclophosphamide and radiation

International Nuclear Information System (INIS)

Looney, W.B.; Hopkins, H.A.; MacLeod, M.S.; Ritenour, E.R.

1979-01-01

The effect of increasing doses of cyclophosphamide (50 to 250 mg/kg) on the time of occurrence of maximal and minimal tumor growth rates, tumor volume reduction, and linear doubling times (LDT) on the solid tumor model H-4-II-E has been determined. Tumor response to cyclophosphamide was classified as class I, tumor regression; class II, pseudo-regression; and class III, slow-down. The overall treatment efficiency (OTE) has been used to assess the magnitude of tumor volume changes after treatment. The maximum OTE occurred after 150 mg/kg of cyclophosphamide. Increasing the dose to 200 and 250 mg/kg of cyclophosphamide resulted in a decrease in OTE. Similar parameters were utilized to measure the effectiveness of increasing doses of local tumor radiation (750, 1500, 2000, 2500, 3000 and 3500R). The major increase in OTE occurs when the radiation dose is increased from 750R to 2000R. Increasing the dose further to 3500R results in smaller incremental increases in the OTE. Results of the study indicate that increasing the cyclophosphamide dose beyond a certain level (i.e., 150 mg/kg) increases mortality and morbidity without concomitant therapeutic benefit. The effects of increasing the dose of local tumor radiation on life span have given results which suggest that increasing the total radiation dose beyond a certain limit is less effective in increasing life span

Theory of atom displacements induced by fast electron elastic scattering in solids

International Nuclear Information System (INIS)

Cruz, C. M.; Pinera, I.; Abreu, Y.; Leyva, A.

2006-01-01

Present contribution deals with the theoretical description of the conditions favoring the occurrence of single fast electron elastic scattering in solids, leading to the displacement of atoms from their crystalline sites. Firstly, the Moliere-Bethe-Goudsmit-Saunderson theory of Multiple Electron Scattering is applied, determining the limiting angle θ l over which the single electron elastic scattering prevails over the multiple one, leading to the evaluation of the total macroscopic cross-section for single electron elastic scattering on the basis of the Mott-Rutherford differential cross-section. On the basis of single electron elastic scattering by atoms in the solid matrix, it was determined the relative number of Atom Displacements produced by the Gamma Radiation as a primary act, as well as the energy and linear momentum of the ejected atoms. The statistical distributions of single electron elastic scattering and of those inducing Atom Displacements at different electron initial energies in comparison with the others electron inelastic scattering channels are discussed, where the statistical sampling methods on the basis of the rejection one where applied simulating different practical situations. (Full text)

Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets.

Science.gov (United States)

de Paula Silva, Neimar; de Souza Reis, Rejane; Cunha, Rafael Garcia; Oliveira, Julio Fernando; da Silva de Lima, Fernanda Cristina; Pombo-de-Oliveira, Maria Socorro; Santos, Marceli Oliveira; de Camargo, Beatriz

2017-04-20

To analyze the relationship between the development of childhood solid tumors and 1) birth weight and 2) fetal growth, using two Brazilian population-based data sets. A case-cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC) and 14 population-based cancer registries (PBCRs) was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS), non-CNS embryonal, and other tumors ("miscellaneous"). Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region). Odds ratios (ORs) with 95% confidence intervals (CIs) were computed using unconditional logistic regression analysis. In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00-1.24) and the adjusted OR was 1.02 (CI: 0.90-1.16) for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00-1.55) and the adjusted OR was 1.04 (CI: 0.82-1.34) for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with "miscellaneous" tumors.

Transport Theory for Kinetic Emission of Secondary Electrons from Solids

DEFF Research Database (Denmark)

Schou, Jørgen

1980-01-01

a solid is derived. To find the former, existing computations for ion slowing down and experimental and theoretical ones for electron bombardment can be utilized. The energy and angular distribution of the secondary electrons and the secondary electron yield are both expressed as products of the deposited...... in the keV region is largely taken into account. The predicted energy and angular distribution agree with absolute spectra for incident electrons, whereas the agreement with absolute spectra for incident protons is less satisfactory. Extrapolation of the energy distribution down to the vacuum level gives...

Existence and consequences of Coulomb pairing of electrons in a solid

International Nuclear Information System (INIS)

Mahajan, S.M.; Thyagaraja, A.

1996-11-01

It is shown from first principles that, in the periodic potential of a crystalline solid, short-range (i.e., screened) binary Coulomb interactions can lead to a two-electron bound state. It is further suggested that these composite bosonic states (charge -2e, and typically spin zero) could mediate an effectively attractive interaction between pairs of conduction electrons close to the Fermi level. This necessarily short range attractive interaction, which is crucially dependent on the band structure of the solid, and is complementary to the phonon-mediated one, may provide a source for the existence and properties of short correlation-length electron pairs (analogous to but distinct from Cooper pairs) needed to understand high temperature superconductivity. Several distinctive and observable characteristics of the proposed pairing scheme are discussed

Strategy of diagnosis and treatment for pediatric solid tumor patients using FDG-PET

International Nuclear Information System (INIS)

Hosono, Ako; Watanabe, Atsuko; Tsuji, Naoko; Kawamoto, Hiroshi; Makimoto, Atsushi; Tateishi, Ukihide; Terauthi, Takashi

2006-01-01

Usefulness of FDG-PET (18F-deoxyglucose PET) was investigated in diagnosis and therapeutic planning of childhood and adolescence malignant solid tumors. Evidence was based on 46 patients (25 males) of ages 5-30 y, involving those with rhabdomyosarcoma (17 cases), Ewing's sarcoma (13), osteosarcoma (5), neuroblastoma (4), Wilms' tumor (2), germinoma (2), and each 1 case of ganglioblastoma, retinoblastoma and hepatoblastoma. In total, they underwent 104 FDG-PET examinations for diagnosis before and during treatment in authors' hospital in the period from January 2005 to February 2006. Evaluations were done with the standard uptake value (SUV, 1 x 1 cm ROI of abnormally high distribution area of radioactivity in the lesion/FDG dose/kg body wt.), by recurrence, by early detection of exacerbation and by follow up of residual tumors, of which typical image findings were herein presented. From the aspects of the present purposes, it was concluded that FDG-PET had advantages of high resolution, short imaging time, quantitative diagnosis (SUV) as well as the tumor detection, and had defects of difficulty of detection of tumors of <1 cm size, of distribution to normal or benign tissues and of difficulty of central nervous system (CNS) imaging. (T.I.)

Pneumothorax as a complication of combination antiangiogenic therapy in children and young adults with refractory/recurrent solid tumors.

Science.gov (United States)

Interiano, Rodrigo B; McCarville, M Beth; Wu, Jianrong; Davidoff, Andrew M; Sandoval, John; Navid, Fariba

2015-09-01

Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy. Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed. Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08-24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (Ppneumothorax was 5.7 weeks (range, 2.4-31). The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

The Range of 1-3 keV Electrons in Solid Oxygen and Carbon Monoxide

DEFF Research Database (Denmark)

Oehlenschlæger, M.; Andersen, H.H.; Schou, Jørgen

1985-01-01

The range of 1-3 keV electrons in films of solid oxygen and carbon monoxide has been measured by a mirror substrate method. The technique used here is identical to the one previously used for range measurements in solid hydrogen and nitrogen. The range in oxygen is slightly shorter than that in n......The range of 1-3 keV electrons in films of solid oxygen and carbon monoxide has been measured by a mirror substrate method. The technique used here is identical to the one previously used for range measurements in solid hydrogen and nitrogen. The range in oxygen is slightly shorter than...

Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

Directory of Open Access Journals (Sweden)

Hyun-Kyoung Kim

Full Text Available BACKGROUND: The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs, which are abundant in solid tumors, can be utilized for identification of rearranged ends. METHOD: As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP microarray method entailing CNB-region refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9% were identified, and two polymerase chain reaction (PCR-amplifiable rearrangements were obtained in six cases (66.7%. And significantly, TNGS-CNB, with its high positive identification rate (82.6% of PCR-amplifiable rearrangements at candidate sites (19/23, just from filtering of aligned sequences, requires little effort for validation. CONCLUSION: Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

Science.gov (United States)

Kim, Hyun-Kyoung; Park, Won Cheol; Lee, Kwang Man; Hwang, Hai-Li; Park, Seong-Yeol; Sorn, Sungbin; Chandra, Vishal; Kim, Kwang Gi; Yoon, Woong-Bae; Bae, Joon Seol; Shin, Hyoung Doo; Shin, Jong-Yeon; Seoh, Ju-Young; Kim, Jong-Il; Hong, Kyeong-Man

2014-01-01

The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends. As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA. Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation. Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

NARCIS (Netherlands)

Raber-Durlacher, J. E.; Weijl, N. I.; Abu Saris, M.; de Koning, B.; Zwinderman, A. H.; Osanto, S.

2000-01-01

The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens

Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

Science.gov (United States)

Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

2016-09-01

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

Mean free path of electrons in rare gas solids

International Nuclear Information System (INIS)

Schwentner, N.

1976-07-01

The energy distribution of photoelectrons of solid Ar, Kr and Xe films with thickness between 10 A and 300 A have been measured in the photon energy range 10 eV to 30 eV using the synchrotron radiation of DESY. By varying the photon energy and the film thickness the dependence of the electron-electron scattering length on the electron kinetic energy has been determined. The mean free path for inelastic electron-electron scattering decreases monotonically from values of the order of 1.000 A at the scattering threshold to values between 1 A and 5 A for electron energies 10 eV above threshold. The observed energy dependence can be understood by a simplified bandstructure and a scattering probability described by a product of density of states. The threshold energy for electron-electron scattering lies between twice the energy of the n = 1 excitons and the sum of bandgap and exciton energy. (HK) [de

Forward electron production in heavy ion-atom and ion-solid collisions

International Nuclear Information System (INIS)

Sellin, I.A.

1984-01-01

A sharp cusp in the velocity spectrum of electrons, ejected in ion-atom and ion-solid collisions, is observed when the ejected electron velocity vector v/sub e/ matches that of the emergent ion vector v/sub p/ in both speed and direction. In ion-atom collisions, the electrons originate from capture to low-lying, projectile-centered continuum states (ECC) for fast bare or nearly bare projectiles, and from loss to those low-lying continuum states (ELC) when loosely bound projectile electrons are available. Most investigators now agree that ECC cusps are strongly skewed toward lower velocities, and exhibit full widths half maxima roughly proportional to v/sub p/ (neglecting target-shell effects, which are sometimes strong). A close examination of recent ELC data shows that ELC cusps are instead nearly symmetric, with widths nearly independent on v/sub p/ in the velocity range 6 to 18 a.u., a result only recently predicted by theory. Convoy electron cusps produced in heavy ion-solid collisions at MeV/u energies exhibit approximately velocity-independent widths very similar to ELC cusp widths. While the shape of the convoy peaks is approximately independent of projectile Z, velocity, and of target material, it is found that the yields in polycrystalline targets exhibit a strong dependence on projectile Z and velocity. While attempts have been made to link convoy electron production to binary ECC or ELC processes, sometimes at the last layer, or alternatively to a solid-state wake-riding model, our measured dependences of cusp shape and yield on projectile charge state and energy are inconsistent with the predictions of available theories. 10 references, 8 figures, 1 table

Many-body effects in X-ray photoemission spectroscopy and electronic properties of solids

International Nuclear Information System (INIS)

Kohiki, S.

1999-01-01

Photoemission from a solid is evidently a many-body process since the motion of each electron cannot be independent of the motions of other electrons. In this article we review the reported many-body effects in X-ray photoemission such as extra-atomic relaxation energy, charge transfer satellite and energy loss structure which are informative in relation to the characteristics of solids. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Polymodification. Short-term hyperglycemia and local hyperthermia in hypoxiradiotherapy of transplantable solid tumors

International Nuclear Information System (INIS)

Kozin, S.V.; Krimker, V.M.; Yarmonenko, S.P.

1984-01-01

Application possibilities of hyperglycemia and local hyperthermia in combination with hypoxiradiotherapy of solid tumors, have been evaluated. The experiments conducted have shown the great possibilities of combined use of radiation, hyperglycemia, hyperthermia, for selective affection of tumours, and application of gaseous hypoxia during irradiation - for simultaneous principal protection of normal tissues. Interaction of all the agents will undoubtedly require a versatile study to develop the optimum regimes of action

Introduction to electronic relaxation in solids: mechanisms and measuring techniques

International Nuclear Information System (INIS)

Bonville, P.

1983-01-01

The fluctuations of electronic magnetic moments in solids may be investigated by several techniques, either electronic or nuclear. This paper is an introduction of the most frequently encountered paramagnetic relaxation mechanisms (phonons, conduction electrons, exchange or dipolar interactions) in condensed matter, and to the different techniques used for measuring relaxation frequencies: electronic paramagnetic resonance, nuclear magnetic resonance, Moessbauer spectroscopy, inelastic neutron scattering, measurement of longitudinal ac susceptibility and γ-γ perturbed angular correlations. We mainly focus our attention on individual ionic fluctuation spectra, the majority of the experimental work refered to concerning rare earth systems [fr

Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets

Directory of Open Access Journals (Sweden)

Neimar de Paula Silva

2017-04-01

Full Text Available ABSTRACT Objective To analyze the relationship between the development of childhood solid tumors and 1 birth weight and 2 fetal growth, using two Brazilian population-based data sets. Methods A case–cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC and 14 population-based cancer registries (PBCRs was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS, non-CNS embryonal, and other tumors (“miscellaneous”. Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region. Odds ratios (ORs with 95% confidence intervals (CIs were computed using unconditional logistic regression analysis. Results In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00–1.24 and the adjusted OR was 1.02 (CI: 0.90–1.16 for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00–1.55 and the adjusted OR was 1.04 (CI: 0.82–1.34 for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. Conclusions The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with “miscellaneous” tumors.

Secondary Electron Emission from Solid Hydrogen and Deuterium Resulting from Incidence of keV Electrons and Hydrogen Ions

DEFF Research Database (Denmark)

Sørensen, H.

1977-01-01

are small, in contrast to what is expected for insulating materials. One explanation is that the secondary electrons lose energy inside the target material by exciting vibrational and rotational states of the molecules, so that the number of electrons that may escape as secondary electrons is rather small....... The losses to molecular states will be largest for hydrogen, so that the SEE coefficients are smallest for solid hydrogen, as was observed. For the incidence of ions, the values of δ for the different molecular ions agree when the number of secondary electrons per incident atom is plotted versus the velocity...... or the stopping power of the incident particles. Measurements were also made for oblique incidence of H+ ions on solid deuterium for angles of incidence up to 75°. A correction could be made for the emission of secondary ions by also measuring the current calorimetrically. At largest energies, the angular...

Recommended Auger-electron kinetic energies for 42 elemental solids

International Nuclear Information System (INIS)

Powell, C.J.

2010-01-01

An analysis is presented of Auger-electron kinetic energies (KEs) from four data sources for 65 Auger transitions in 45 elemental solids. For each data source, a single instrument had been used to measure KEs for many elements. In order to compare KEs from two sources, it was necessary to recalibrate the energy scales of each instrument using recommended reference data. Mean KEs are given for most of the Auger transitions for which there were at least two independent measurements and for which differences from the mean KEs were considered acceptably small. In several cases, comparisons were made to published KE data to resolve discrepancies. We are able to recommend mean KEs for 59 Auger transitions from 42 elemental solids and to provide estimates of the uncertainties of these KEs. This compilation should be useful for the determination of chemical shifts of Auger peaks in Auger electron spectroscopy and X-ray photoelectron spectroscopy.

Attosecond photoelectron spectroscopy of electron transport in solids

International Nuclear Information System (INIS)

Magerl, Elisabeth

2011-01-01

Time-resolved photoelectron spectroscopy of condensed matter systems in the attosecond regime promises new insights into excitation mechanisms and transient dynamics of electrons in solids. This timescale became accessible directly only recently with the development of the attosecond streak camera and of laser systems providing few-cycle, phase-controlled laser pulses in the near-infrared, which are used to generate isolated, sub-femtosecond extreme-ultraviolet pulses with a well-defined timing with respect to the near-infrared pulse. Employing these pulses, the attosecond streak camera offers time resolutions as short as a few 10 attoseconds. In the framework of this thesis, a new, versatile experimental apparatus combining attosecond pulse generation in gases with state of the art surface science techniques is designed, constructed, and commissioned. Employing this novel infrastructure and the technique of the attosecond transient recorder, we investigate transport phenomena occurring after photoexcitation of electrons in tungsten and rhenium single crystals and show that attosecond streaking is a unique method for resolving extremely fast electronic phenomena in solids. It is demonstrated that electrons originating from different energy levels, i.e. from the conduction band and the 4f core level, are emitted from the crystal surface at different times. The origin of this time delay, which is below 150 attoseconds for all studied systems, is investigated by a systematic variation of several experimental parameters, in particular the photon energy of the employed attosecond pulses. These experimental studies are complemented by theoretical studies of the group velocity of highly-excited electrons based on ab initio calculations. While the streaking technique applied on single crystals can provide only information about the relative time delay between two types of photoelectrons, the absolute transport time remains inaccessible. We introduce a scheme of a reference

Attosecond photoelectron spectroscopy of electron transport in solids

Energy Technology Data Exchange (ETDEWEB)

Magerl, Elisabeth

2011-03-31

Time-resolved photoelectron spectroscopy of condensed matter systems in the attosecond regime promises new insights into excitation mechanisms and transient dynamics of electrons in solids. This timescale became accessible directly only recently with the development of the attosecond streak camera and of laser systems providing few-cycle, phase-controlled laser pulses in the near-infrared, which are used to generate isolated, sub-femtosecond extreme-ultraviolet pulses with a well-defined timing with respect to the near-infrared pulse. Employing these pulses, the attosecond streak camera offers time resolutions as short as a few 10 attoseconds. In the framework of this thesis, a new, versatile experimental apparatus combining attosecond pulse generation in gases with state of the art surface science techniques is designed, constructed, and commissioned. Employing this novel infrastructure and the technique of the attosecond transient recorder, we investigate transport phenomena occurring after photoexcitation of electrons in tungsten and rhenium single crystals and show that attosecond streaking is a unique method for resolving extremely fast electronic phenomena in solids. It is demonstrated that electrons originating from different energy levels, i.e. from the conduction band and the 4f core level, are emitted from the crystal surface at different times. The origin of this time delay, which is below 150 attoseconds for all studied systems, is investigated by a systematic variation of several experimental parameters, in particular the photon energy of the employed attosecond pulses. These experimental studies are complemented by theoretical studies of the group velocity of highly-excited electrons based on ab initio calculations. While the streaking technique applied on single crystals can provide only information about the relative time delay between two types of photoelectrons, the absolute transport time remains inaccessible. We introduce a scheme of a reference

Safty and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors

International Nuclear Information System (INIS)

Zhai Yirui; Feng Qinfu; Li Minghui

2010-01-01

Objective: To investigate the safety and acute toxicities of intraoperative electron radiotherapy for patients with abdominal tumors. Methods: From May 2008 to August 2009, 52 patients with abdominal tumors were treated with intraoperative electron radiotherapy, including 14 patients with breast cancer,19 with pancreatic cancer, 3 with cervical cancer, 4 with ovarian cancer, 6 with sarcoma, and 6 with other tumors. Fifteen patients were with recurrent tumors. The intraoperative radiotherapy was performed using Mobetron mobile electron accelerator, with total dose of 9 - 18 Gy. In all, 29, 4 and 19 patients received complete resection, palliative resection and surgical exploration, respectively. The complications during the operations and within 6 months after operations were graded according to Common Terminology Criteria for Adverse Events v3.0 (CTC 3.0). Results: The median duration of surgery was 190 minutes. Intraoperative complications were observed in 5 patients, including 3 with hemorrhage, 1 with hypotension,and 1 with hypoxaemia, all of which were treated conservatively. The median hospitalization time and time to take out stitches was 12 and 13 days, respectively. And the in-hospital mortality was 4% (2/52). Twenty-four patients suffered post-operative adverse events, including 3 postoperative infections. With a median follow-up time of 183 days, 20% of patients suffered from grade 3 to 5 adverse events, with hematological toxicities being the most common complication, followed by bellyache. Grade 1 and 2 toxicities which were definitely associated with intraoperative radiotherapy was 28% and 4%, respectively. None of grade 3 to 5 complications were proved to be caused by intraoperative radiotherapy. Conclusions: Intraoperative electron radiotherapy is well tolerable and could be widely used for patients with abdominal tumors, with a little longer time to take out stitches but without more morbidities and toxicities compared surgery alone. (authors)

Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial.

Science.gov (United States)

Pramanik, Raja; Agarwala, Sandeep; Gupta, Yogendra Kumar; Thulkar, Sanjay; Vishnubhatla, Sreenivas; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

2017-09-01

Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than

Investigation of the effects of long-term infusion of 125I-iododeoxyuridine on tumor growth in mice (solid mouse tumor sarcoma-180)

International Nuclear Information System (INIS)

Wirtz, F.

1987-05-01

The present experiments were designed to test the therapeutic qualification of 125 I incorporated in DNA of tumor cells. The tumor-host system used was the solid mouse tumor sarcoma-180 growing on female albino mice (NMRI). A device was built which makes it possible to intravenously infuse tumor bearing mice with solutions of 125 IUdR for several weeks. Three or, respectively, 5 days before the onset of the infusions the mice were inocculated into the right hind leg with 3x10 5 tumor cells in 0.1 ml physiological salt solution. The total activity administered per mouse was 100 μCi infused during a period of 10 days. After termination of the infusions tumor sizes and retained radioactivities were measured every 5 days until death of the animals occured. In comparison with tumors of control animals tumors of mice infused with 125 IUdR showed a mean retardation in growth of about 27% of the volumes of control tumors during the total period of post-infusion observation (25 days). Extension of life expectancy and an increase of the rate of final tumor regression did not occur. Likewise, no significant differences were observed between tumors which were 3 or 5 days old on the first day of infusion. After termination of the infusions the residual whole-body radioactivity per mouse was about 1% of the total activity infused per animal. This was in good agreement with calculations considering rates of incorporation and excretion and confirmed earlier assumptions that only about 5% of the administered IUdR is incorporated initially. The number further confirmed that, during the first 10 days after incorporation, the daily loss of activity - due to cell death - is about 30%. Control animals without tumors showed a faster decrease of incorporated activity or, respectively, loss of cells than tumor bearing mice. This difference could in part be explained by an exhaution of the short-lived cell populations of the reticulo-endothelial system of tumor bearing animals. (orig

Antitumor Effect of Selenium and Modified Pectin Nano Particles and Gamma Radiation on Ehrilch Solid Tumor in Female Mice

International Nuclear Information System (INIS)

Mansour, S. Z.; Anis, L.M.; EI- Batal, A.I.

2010-01-01

Selenium nano particle (Nano- Se) is a novel Se species with novel biological activities with low toxicity. The aim of the present work was to evaluate the antitumor activity of a novel Nano- Se compound with or without gamma irradiation of female mice. Selenium size- controlled Nano-Se was prepared by a simple method by adding modified pectin to the selenious acid and ascorbic acid. The antitumor activity of Selenium and Modified Pectin Nano Particles (Se-Mp- NPs) were evaluated against Ehrilch ascites carcinoma (In vitro) and Ehrilch solid tumor model (In vivo). The antioxidant states of the novel compound were assessed measuring parameters in blood and tumor tissue of female mice. Malonaldehydoyl (MDA) end product of lipid peroxidation was evaluated in plasma and tumor tissue. Glutathione -S- transferase (GST) and cytochrome P450 (Cyto P450) were determined in tumor tissue homogenate. Tumor necrosis factor alpha (TNF- a) concentration and interleukin 10 (IL- 10) concentrations was evaluated in plasma of female mice. The effect of tumor inoculation and different treatments on liver enzymes (ALT and AST) and kidney Function (urea and creatinine) were detected in the plasma of animals. Apoptosis was shown and estimated in tumor tissue of animals histopathological of tumor in different groups of mice were examined. Ehrilch solid tumor induced a significant increase in MDA content, GSH-Px and GST activities level and in the amount of metabolites of CYP 450. Moreover, a significant decrease was observed in GSH content, SOD activity level in the tumor tissue, INF- a concentration, IL- 10 concentration in the plasma. Also, a significant alteration in kidney and liver functions was occurred as compared to control group. The results showed a significant antitumor activity of selenium and Modified Pectin Nano Particles (Se-Mp- NPs) at the concentration 2.25 μg / ml was 70%

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

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Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

2015-01-01

We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

Electron holography for fields in solids: Problems and progress

International Nuclear Information System (INIS)

Lichte, Hannes; Börrnert, Felix; Lenk, Andreas; Lubk, Axel; Röder, Falk; Sickmann, Jan; Sturm, Sebastian; Vogel, Karin; Wolf, Daniel

2013-01-01

Electron holography initially was invented by Dennis Gabor for solving the problems raised by the aberrations of electron lenses in Transmission Electron Microscopy. Nowadays, after hardware correction of aberrations allows true atomic resolution of the structure, for comprehensive understanding of solids, determination of electric and magnetic nanofields is the most challenging task. Since fields are phase objects in the TEM, electron holography is the unrivaled method of choice. After more than 40 years of experimental realization and steady improvement, holography is increasingly contributing to these highly sophisticated and essential questions in materials science, as well to the understanding of electron waves and their interaction with matter. - Highlights: • We review the development of the method of electron holography. • We outline the role of information content as guideline. • We outline the improvements of the method. • We sketch the future instrumental development. • We summarize the still existing problems to solve

Photoelectron spectroscopy and Auger electron spectroscopy of solids and surfaces

International Nuclear Information System (INIS)

Kowalczyk, S.P.

1976-01-01

The use of photoelectron spectroscopy, primarily x-ray photoelectron spectroscopy, to obtain information on the electronic structure of a wide variety of solids (especially the bulk electronic structure of solids) is covered. Both valence band and core-level spectra, as well as a few cases of photon excited Auger electron spectroscopy, are employed in the investigations to derive information on N(E). The effect of several modulations inherent in the measured I(E)'s, such as final state band structure, cross section, and relaxation, is discussed. Examples of many-electron interactions in PES are given. Some experimental aspects of PES and AES studies are given with emphasis on sample preparation techniques. Multiple splitting of core levels is examined using the Mn levels in MnF 2 as a detailed case study. Core level splittings in transition metals, rare earth metals, transition metal halides and several alloys are also reported. The application of PES to the study of the chemical bond in some crystalline semiconductors and insulators, A/sup N/B/sup 8-N/ and A/sup N/B/sup 10-N/ compounds is treated, and a spectroscopic scale of ionicity for these compounds is developed from the measured ''s-band'' splitting in the valence band density of states

Defect creation in solids by a decay of electronic excitations

International Nuclear Information System (INIS)

Klinger, M.I.; Lushchik, Ch.B.; Mashovets, T.V.; Kholodar', G.A.; Shejnkman, M.K.; Ehlango, M.A.; Kievskij Gosudarstvennyj Univ.; AN Ukrainskoj SSR, Kiev. Inst. Poluprovodnikov)

1985-01-01

A new type of radiationless transitions in nonmetallic solids accompanied by neither the extraction of a heat nor the luminescence, but by a large (in comparison with the interatomic distance) displacements of a small number of atoms is discussed. A classification is given of the instabilities (electrostatic, electron-vibrational, structural) leading to a creation of the defects in crystalline and glassy solids. The processes of the defect creation, due to both the decay of self-trapped excitions in ionic crystals and the multiple ionization of atoms near the pre-existing charged centres in semiconductor are described. The mechanisms of the complex defects reconstruction in semiconductors by nonequilibrium charge carriers and by an electron-hole recombination are discussed. The role of charge carriers in a thermal defect generation is considered. A mechanism of the peculiar defect creation in glassy semiconductors is discussed

Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.

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Dickson K Kirui

Full Text Available BACKGROUND: Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs. We also determined the optimal time window at which maximal accumulation occur. RESULTS: In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2 amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion. CONCLUSIONS: Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.

Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

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Xiaonan Zhang

2015-11-01

Full Text Available The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an “Achilles heel” for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations.

Tumor induction and hair follicle damage for different electron penetrations in rat skin

International Nuclear Information System (INIS)

Burns, F.J.; Sinclair, I.P.; Albert, R.E.; Vanderlaan, M.

1976-01-01

The penetration and dose of an electron beam were varied in an attempt to locate the depth in growing-phase rat skin where irradiation was most effective in inducing tumors and morphological damage to the hair follicles. The hair was plucked to initiate the growing phase of the hair cycle, and 12 days later the dorsal skin was irradiated with electrons penetrating 0.5, 1.0, or 2.0 mm at doses from 500 to 4000 rad. Differences in the curves of tumor incidence as a function of dose for different penetrations were best resolved by plotting the results against the 0.4 mm dose, while comparable curves for destruction of the follicles were best resolved by the 0.8 mm dose. Since 0.8 mm corresponded approximately to the depth of the follicles, these results indicated that the target tissues for follicular damage and tumor induction were separated in depth and that the target for tumor induction was probably located in the region above or near the midpoint of the follicles. When the radiation penetrated sufficiently to reach the entire follicle, the number of tumors produced was not significantly greater than the number observed previously in resting-phase skin, and it was inferred that the additional size and greater mitotic activity of the growing-phase follicles at the time of irradiation did not increase the probability of tumor induction

Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

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A. Silvani

2013-01-01

Full Text Available Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC and liposomal antitumor agents (liposomal AraC. Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

A Case of Recurrent Solid Pseudopapillary Tumor of the Pancreas with Involvement of the Spleen and Kidney

OpenAIRE

Park, Sang Eun; Park, Nam Sook; Chun, Jae Min; Park, Nam Whan; Yang, Young Joon; Yun, Gak Won; Lee, Hyo Jin; Yun, Hwan Jung; Jo, Deog Yeon; Song, Kyu Sang; Kim, Samyong

2006-01-01

Solid pseudopapillary tumor of the pancreas (SPTP) is a rare primary pancreatic tumor of an unknown etiology that is usually diagnosed in adolescent girls and young women. Most SPTPs are considered to be benign and only rarely metastasize. We report here on a 27-year old woman with recurrent SPTP with involvement of both the spleen and left kidney at the time of the initial diagnosis, and with aggressive behavior. In July 1995, she was admitted with abdominal discomfort and mass. She underwen...

Introduction to the Physics of Electrons in Solids

CERN Document Server

Alloul, Henri

2011-01-01

This textbook sets out to enable readers to understand fundamental aspects underlying quantum macroscopic phenomena in solids, primarily through the modern experimental techniques and results. The classic independent-electrons approach for describing the electronic structure in terms of energy bands helps explain the occurrence of metals, insulators and semiconductors. It is underlined that superconductivity and magnetism can only be understood by taking into account the interactions between electrons. The text recounts the experimental observations that have revealed the main properties of the superconductors and were essential to track its physical origin. While fundamental concepts are underlined, those which are required to describe the high technology applications, present or future, are emphasized as well. Problem sets involve experimental approaches and tools which support a practical understanding of the materials and their behaviour. Key features of this textbook are: - Modern treatment of condensed ...

Electron capture and loss to continuum states in gases and solids

International Nuclear Information System (INIS)

Sellin, I.A.; Laubert, R.

1981-01-01

A key feature of our experimental procedure is the easy interchange of short gaseous and thin solid targets at the same physical position, with all apparatus aperture sizes, dimensions, positions, and other experimental details unaltered. It has therefore been possible to cancel most systematic apparatus effects in comparing gaseous and solid target results. By using single ion-atom collision techniques, by using bare and few-electron ions of appreciably higher charge than heretofore, by extending the velocity range of measurement appreciably above that of earlier experiments, and by studying charge-state variation over an appreciably wider range than used previously, we have been able to test experimentally features of continuum electron-capture and -loss theories which have been inaccessible in previous experiments. (orig./TW)

Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

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Neimar de Paula Silva

Full Text Available Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics.A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma. Children aged <6 years were selected. Adjustments were made for potential confounders. Odds ratios (OR with 95% confidence intervals (CI were computed by unconditional logistic regression analysis using SPSS.Males, high maternal education level, and birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01. Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma.This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

Application of 10BSH entrapped transferrin-PEG-liposome to boron neutron-capture therapy (BNCT) for solid tumor

International Nuclear Information System (INIS)

Maruyama, K.; Ishida, O.; Iwatsuru, M.; Yanagie, H.; Eriguchi, M.; Kobayashi, H.

2000-01-01

The successful treatment of cancer by BNCT requires the selective concentration of 10 B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of 10 B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vivo, and were internalized by receptor-mediated endocytosis. 10 B-PEG-liposomes and 10 B-TF-PEG-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of 10 B content in tumor. After thermal neutron irradiation of mice injected with 10 B-PEG-liposomes or 10 B-TF-PEG-liposome, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of 10 B TF-PEG-liposome can increase the intracellular retention of 10 B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. (author)

Differentiation of Solid Renal Tumors with Multiparametric MR Imaging.

Science.gov (United States)

Lopes Vendrami, Camila; Parada Villavicencio, Carolina; DeJulio, Todd J; Chatterjee, Argha; Casalino, David D; Horowitz, Jeanne M; Oberlin, Daniel T; Yang, Guang-Yu; Nikolaidis, Paul; Miller, Frank H

2017-01-01

Characterization of renal tumors is critical to determine the best therapeutic approach and improve overall patient survival. Because of increased use of high-resolution cross-sectional imaging in clinical practice, renal masses are being discovered with increased frequency. As a result, accurate imaging characterization of these lesions is more important than ever. However, because of the wide array of imaging features encountered as well as overlapping characteristics, identifying reliable imaging criteria for differentiating malignant from benign renal masses remains a challenge. Multiparametric magnetic resonance (MR) imaging based on various anatomic and functional parameters has an important role and adds diagnostic value in detection and characterization of renal masses. MR imaging may allow distinction of benign solid renal masses from several renal cell carcinoma (RCC) subtypes, potentially suggest the histologic grade of a neoplasm, and play an important role in ensuring appropriate patient management to avoid unnecessary surgery or other interventions. It is also a useful noninvasive imaging tool for patients who undergo active surveillance of renal masses and for follow-up after treatment of a renal mass. The purpose of this article is to review the characteristic MR imaging features of RCC and common benign renal masses and propose a diagnostic imaging approach to evaluation of solid renal masses using multiparametric MR imaging. © RSNA, 2017.

Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

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Valentin Lestelle

2015-10-01

Full Text Available We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

2015-01-01

Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10 −9 ), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10 −3 ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection

Epidemiology and Outcomes of Bloodstream Infections in Patients With Solid Tumors in a Central American Population at Mexico Hospital, San Jose, Costa Rica

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Jorge Calvo-Lon

2017-12-01

Full Text Available Purpose: Bloodstream infections (BSIs are an important cause of mortality in patients with solid tumors. We conducted a retrospective study to evaluate the epidemiologic profile and mortality of patients with solid tumors who have BSIs and were admitted to Mexico Hospital. This is the first study in Costa Rica and Central America describing the current epidemiologic situation. Methods: We analyzed the infectious disease database for BSIs in patients with solid tumors admitted to Mexico Hospital from January 2012 to December 2014. Epidemiology and mortality were obtained according to microorganism, antibiotic sensitivity, tumor type, and presence of central venous catheter (CVC. Descriptive statistics were used. Results: A total of 164 BSIs were recorded, the median age was 58 years, 103 patients (63% were males, and 128 cases of infection (78% were the result of gram-negative bacilli (GNB. Klebsiella pneumoniae (21%, Escherichia coli (21%, and Pseudomonas aeruginosa (15% were the most common microorganisms isolated. Gram-positive cocci (GPC were found in 36 patients, with the most frequent microorganisms being Staphylococcus aureus (10% and Staphyloccocus epidermidis (6%. With respect to tumor type, BSIs were more frequent in the GI tract (57% followed by head and neck (9% and genitourinary tract (8%. Regarding antibiotic susceptibility, only 17% (GNB expressed extended-spectrum beta-lactamase and 12% (GPC had methicillin resistance. Patients with CVCs (n = 59 were colonized mainly by GNB (78%. Overall the mortality rate at 30 days was about 30%. Conclusion: GNB are the most frequent cause of BSIs in solid tumors and in patients with CVCs. GI cancers had more BSIs than other sites. Mortality and antibiotic sensitivity remained stable and acceptable during this observational period in this Latin American population.

Emission of low-energetic electrons in collisions of heavy ions with solid targets

International Nuclear Information System (INIS)

Lineva, Natallia

2008-07-01

At the UNILAC accelerator, we have initiated a project with the objective to investigate lowenergy electrons, emitted from solid, electrically conductive targets after the impact of swift light and heavy ions. For this purposes, we have installed, optimized, and put into operation an electrostatic toroidal electron spectrometer. First, investigations of electrons, emitted from solid-state targets after the bombardment with a monochromatic electron beam from an electron gun, has been carried out. The proposed method combines the results of the measurements with the results of dedicated Monte Carlo simulations. The method has been elaborated in a case study for carbon targets. The findings have been instrumental for the interpretation of our measurements of electrons emitted in collisions of swift ions with the same carbon targets. Our investigations focused on following ion beams: protons and (H + 3 )-molecules of the same energy, as well as on carbon ions with two different energies. Thin carbon, nickel, argon and gold foils has been used as targets. Electrons in the energy range between 50 eV and 1 keV have been investigated. The measured electron distributions, both integral as well as differential with respect to the polar angle, have been compared to simple standard theories for gases as well as to the results of TRAX simulations, the latter being based on data from gaseous targets. Dedicated TRAX simulations have been performed only for the carbon targets, applying the method mentioned above. Within our experimental uncertainties, we observe a good agreement of the measured and TRAX simulated data. That leads us to the conclusion that - as a first order approximation - the electron emission pattern from ion-atom collisions in solid-state targets and the one from single collisions in gases are similar. (orig.)

Pattern of malignant solid tumors and lymphomas in children in the east delta of Egypt: A five-year study.

Science.gov (United States)

Hesham, Mervat; Atfy, Mervat; Hassan, Tamer; Abdo, Mohamed; Morsy, Saed; El Malky, Mohamed; Latif, Dalia Abdel

2014-11-01

Worldwide, the incidence and mortality rates of childhood cancers differ. The study of incidence patterns and survival rates in childhood malignancies is important in aiding in the planning of treatment centers and in obtaining further information with regard to the etiology. Few studies have investigated the survival in cases of childhood solid tumors in Egypt. The aim of the current study was to evaluate the patterns, frequency and outcome of solid tumors and lymphomas in children admitted to and followed up at the Pediatric Oncology Department of Zagazig University Hospital (Zagazig, Egypt) over a duration of 5 years (January 2004 to December 2008). A retrospective study was conducted, which included 155 children with solid tumors and lymphomas. The medical records were reviewed and the relevant data collected, in particular, those concerning demographic, clinical, histopathological, laboratory and imaging data as well as the treatment plans and outcomes. The mean age of patients was 5.6±3.04 years at diagnosis. The patients comprised 94 males and 61 females. Non-Hodgkin lymphoma (NHL) was the most common tumor type, followed by neuroblastoma (31.0 and 29.0%, respectively). When patients were stratified in terms of age (<5, ≥5 but <10, and ≥10 years), the <5-years-of-age group exhibited the greatest number of patients. Fever, pallor and pain were the most frequent initial clinical presentations among the patients and stage II was the most common stage (39.1%) followed by stage IV, III and I (35.0, 20.3 and 5.6% respectively). The overall 5-year survival rate in the study group was 66.7%. The survival rate was significantly higher in patients with Wilm's tumor and Hodgkin lymphoma, followed by NHL (92.0, 88.0 and 72.0%, respectively; P<0.001), while the mortality rate was significantly higher in patients with neuroblastoma (P<0.001). In conclusion, NHL and neuroblastoma were the most common tumors; the survival rates were higher in patients with Wilm's tumor

Solid pseudopapillary tumors of the pancreas: 27 cases from a single institution

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ZHOU Haiyang

2013-01-01

Full Text Available ObjectiveTo summarize the clinicopathologic features and treatment outcomes of solid pseudopapillary tumors (SPTs of the pancreas. MethodsTwenty-seven cases of SPT of the pancreas admitted for treatment to the Peking University Cancer Hospital between September 2008 and September 2012 were retrospectively analyzed. ResultsThe majority of the pancreatic SPT patients were young adults (median age: 29 years old and females (85.2%. All 27 patients were treated with surgical resection using pancreaticoduodenectomy (n=4, duodenum preserving pancreatic tumor resection (n=6, middle pancreatectomy (n=5, distal pancreatectomy (n=5, or distal pancreatectomy plus splenectomy (n=7. The minimum tumor diameter was 1.5 cm, the maximum diameter was 12.0 cm, and the average diameter was 5.4 cm. Twelve patients developed pancreatic leakage and pyrexia following the operation. One patient suffered splenic artery hemorrhage. All 27 patients survived and completed follow-up. Only one patient developed recurrence, which was treated by a second surgical resection, and all other patients showed no clinical signs of recurrence or metastasis. ConclusionSPT of the pancreas has uncertain malignant potential with good prognosis. Radical resection with preservation of the surrounding tissues is an effective and safe treatment for SPT.

Somatic Genetic Variation in Solid Pseudopapillary Tumor of the Pancreas by Whole Exome Sequencing

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Meng Guo

2017-01-01

Full Text Available Solid pseudopapillary tumor of the pancreas (SPT is a rare pancreatic disease with a unique clinical manifestation. Although CTNNB1 gene mutations had been universally reported, genetic variation profiles of SPT are largely unidentified. We conducted whole exome sequencing in nine SPT patients to probe the SPT-specific insertions and deletions (indels and single nucleotide polymorphisms (SNPs. In total, 54 SNPs and 41 indels of prominent variations were demonstrated through parallel exome sequencing. We detected that CTNNB1 mutations presented throughout all patients studied (100%, and a higher count of SNPs was particularly detected in patients with older age, larger tumor, and metastatic disease. By aggregating 95 detected variation events and viewing the interconnections among each of the genes with variations, CTNNB1 was identified as the core portion in the network, which might collaborate with other events such as variations of USP9X, EP400, HTT, MED12, and PKD1 to regulate tumorigenesis. Pathway analysis showed that the events involved in other cancers had the potential to influence the progression of the SNPs count. Our study revealed an insight into the variation of the gene encoding region underlying solid-pseudopapillary neoplasm tumorigenesis. The detection of these variations might partly reflect the potential molecular mechanism.

Use of magnetic resonance imaging to detect neoplastic meningitis: Limited use in leukemia and lymphoma but convincing results in solid tumors

International Nuclear Information System (INIS)

Pauls, Sandra; Fischer, Ann-Cathrin; Brambs, Hans-Jürgen; Fetscher, Sebastian; Höche, Wolfram; Bommer, Martin

2012-01-01

Background: An early diagnosis of meningitis is important to improve patients’ survival. Data about a direct comparison of cerebrospinal fluid cytology (CSF-cytology) and MRI are very limited. Therefore, the aim of this study was to compare these two diagnostic modalities in diagnosing meningitis in patients with hematopoietic and solid malignancies. Methods: In 68 patients suspicious for neoplastic meningitis, cytology and MRI (1.5 T) was performed. The meningeal, pial or intraparenchymal hyperintense signal or contrast enhancement was correlated to the final CNS diagnosis and to cytology. Results: 44 patients (64.7%) had neoplastic meningitis, 21 patients (30.9%) had non-neoplastic meningitis. The sensitivity to diagnose meningeal disease was 49.2% for MRI and 95.4% for cytology (p < 0.001). In patients with neoplastic meningitis, sensitivity was 45.5% for MRI and 93.2% for cytology (p < 0.001). In patients with infectious meningitis, sensitivity was 57.1% for MRI and 100% for cytology (p = 0.0013). In patients with solid tumors, the sensitivity was 84.6% for both diagnostic methods. The sensitivity for MRI was low in patients with leukemia (20.0%) and lymphoma (37.5%). The positive predictive value (PPV) for MRI to differentiate infectious from neoplastic meningitis was high in patients with infectious meningitis (75.0%), in patients with lymphoma (83.3%), and in patients with solid tumors (72.7%). Ppv was low in patients with leukemia (33.3%). Conclusion: Diagnostic value of MRI for diagnosing meningitis is especially limited in patients with hematopoietic malignancies. MRI better detected leptomeningeal involvement caused by solid tumors than by leukemia or lymphoma. The ppv to specify neoplastic meningitis depends on tumor subtype.

Whole-body MRI in comparison to skeletal scintigraphy for detection of skeletal metastases in patients with solid tumors

International Nuclear Information System (INIS)

Ghanem, N.; Altehoefer, C.; Winterer, J.; Schaefer, O.; Bley, T.A.; Langer, M.; Kelly, T.; Moser, E.

2004-01-01

The aim of this study was to compare the diagnostic efficacy of whole-body magnetic resonance imaging (WB-MRI) as a new and rapid examination technique with skeletal scintigraphy for detection of skeletal metastases from solid tumors. In 129 patients with solid malignant tumors, WB-MRI was performed for individual comparison with skeletal scintigraphy. Examinations were performed with the innovative AngioSURF trademark rolling table with integrated phased array surface coil and coronary TIRM sequences for different body regions. The results for WB-MRI and skeletal scintigraphy were concordant in 81% of the cases, whereby both procedures excluded skeletal metastases in 43%. WB-MRI and skeletal scintigraphy demonstrated skeletal metastases in 38% of the cases, whereby WB-MRI provided more comprehensive findings in 45%. In 12% of the cases, skeletal scintigraphy was superior to WB-MRI and in 19% the findings were discordant, whereby WB-MRI detected skeletal metastases in 15 cases which had not been found on skeletal scintigraphy. In nine cases, skeletal scintigraphy was positive when the WB-MRI was negative. In 60% of the cases, WB-MRI evidenced tumor-associated findings. WB-MRI represents a promising new staging technique for detection of skeletal metastases, which is more sensitive in many cases than skeletal scintigraphy in detecting and assessing the extent of skeletal metastases - and tumor-associated findings that are relevant for treatment strategy. (orig.) [de

Characterization of Compounds with Tumor-Cell Proliferation Inhibition Activity from Mushroom (Phellinus baumii) Mycelia Produced by Solid-State Fermentation.

Science.gov (United States)

Zhang, Henan; Shao, Qian; Wang, Wenhan; Zhang, Jingsong; Zhang, Zhong; Liu, Yanfang; Yang, Yan

2017-04-27

The inhibition of tumor-cell proliferationbyan organicsolvent extract from the solid-state fermentation of Phellinus baumii mycelia inoculated in rice medium was investigated in vitro. The active compounds inhibiting tumor-cell proliferation were characterized. Results revealed that all (petroleum ether, chloroform, ethyl acetate, and butanol) fractions inhibited tumor-cell proliferation in a dose-dependent fashion. The ethyl acetate extract had the highest inhibitory effecton tumor-cell proliferation, and the butanol fraction had the lowest. Six compounds were isolated and purified from the ethyl acetate extract of P. baumii mycelia by the tandem application of silica-gel column chromatography (SGCC), high-speed countercurrent chromatography (HSCCC), and preparative HPLC. These compounds were identified by NMR and electrospray ionization-mass spectrometry (ESI-MS) spectroscopic methods as ergosterol (RF1), ergosta-7,22-dien-3β-yl pentadecanoate (RF3), 3,4-dihydroxy benzaldehyde(RF6), inoscavinA (RF7), baicalein(RF10), and 24-ethylcholesta-5,22-dien-3β-ol (RF13). To further clarify the activity of these compounds, the cell-proliferation-inhibition tests of these compounds on various tumor cells were carried out and evaluatedin vitro. Results suggested that compounds RF6, RF7, and RF10 had potent inhibition effects on the proliferation of a series of tumor cell lines, including K562, L1210, SW620, HepG2, LNCaP, and MCF-7cells. These findings indicated that P. baumii mycelia produced by solid-state fermentation in rice canbe used to obtain active compounds with the ability to inhibittumor-cell proliferation.

The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors

International Nuclear Information System (INIS)

Lee, Carol M; Tannock, Ian F

2010-01-01

Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity. Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with ERBB2 (231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2. The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly. Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors

MR imaging of malignant ovarian tumors

International Nuclear Information System (INIS)

Kim, Jun Ho; Kang, Heoung Keun; Moon, Woong Jae; Seo, Jeong Jin; Kim, Jae Kyu; Choi, Ho Sun

1994-01-01

To evaluate MRI findings of malignant ovarian tumors. MRI findings were retrospectively reviewed in 25 patients with surgically confirmed 30 malignant ovarian tumors(common epithelial tumor; 23, sex cord stromal tumor; 2, endo dermal sinus tumor; 1, metastatic tumor; 4). The findings evaluated were the lesion size, solid and/or cystic component, wall thickness, septal thickness, necrosis, invasion of adjacent organ, ascites, and adenopathy. MRI findings of the malignant ovarian tumors were as follow: Size of lesion was 5-35cm(mean 14cm); solid component was present in 80%(24/30); wall thickness was more than 3mm in 90%(27/30); septal thickness was more than 3mm in 70%(21/30); tumor necrosis was present in 40%(12/30%); invasion of adjacent organ was present in 76%(19/25); ascites was present in 56%(14/25); lymphadenopathy was present in 24% (6/25). MRI findings of absence of solid component(6/6), even wall and septal thickness(7/7, 19/19) were found only in epithelial tumors. Uneven septal thickness more than 3mm(7/11) was a predominant MRI findings of non-epithelial tumors. Well-defined cystic lesion within solid component was seen in Krukenberg tumors. Evaluation of the lesion size, internal architecture, invasion of adjacent organ, ascites, and lymphadenopathy in MRI would enable diagnosis of malignant ovarian tumors and could lead to possible differential diagnosis of epithelial tumors from non-epithelial tumors

PREFACE: International Workshop on Dirac Electrons in Solids 2015

Science.gov (United States)

Ogata, M.; Suzumura, Y.; Fuseya, Y.; Matsuura, H.

2015-04-01

It is our pleasure to publish the Proceedings of the International Workshop on Dirac Electrons in Solids held in University of Tokyo, Japan, for January 14-15, 2015. The workshop was organized by the entitled project which lasted from April 2012 to March 2015 with 10 theorists. It has been supported by a Grand-in-Aid for Scientific Research (A) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. The subjects discussed in the workshop include bismuth, organic conductors, graphene, topological insulators, new materials including Ca3PbO, and new directions in theory (superconductivity, orbital susceptibility, etc). The number of participants was about 70 and the papers presented in the workshop include four invited talks, 16 oral presentations, and 23 poster presentations. Dirac electron systems appear in various systems, such as graphene, quasi-two-dimensional organic conductors, bismuth, surface states in topological insulators, new materials like Ca3PbO. In these systems, characteristic transport properties caused by the linear dispersion of Dirac electrons and topological properties, have been extensively discussed. In addition to these, there are many interesting research fields such as Spin-Hall effect, orbital diamagnetism due to interband effects, Landau levels characteristic to Dirac dispersion, anomalous interlayer transport phenomena and magnetoresistance, the effects of spin-orbit interaction, and electron correlation. The workshop focused on recent developments of theory and experiment of Dirac electron systems in the above materials. We note that all papers published in this volume of Journal of Physics: Conference Series were peer reviewed. Reviews were performed by expert referees with professional knowledge and high scientific standards in this field. Editors made efforts so that the papers may satisfy the criterion of a proceedings journal published by IOP Publishing. We hope that all the participants of the workshop

Low energy electron diffraction (LEED) and sum frequency generation (SFG) vibrational spectroscopy studies of solid-vacuum, solid-air and solid-liquid interfaces

Energy Technology Data Exchange (ETDEWEB)

Hoffer, Saskia [Univ. of California, Berkeley, CA (United States)

2002-01-01

Electron based surface probing techniques can provide detailed information about surface structure or chemical composition in vacuum environments. The development of new surface techniques has made possible in situ molecular level studies of solid-gas interfaces and more recently, solid-liquid interfaces. The aim of this dissertation is two-fold. First, by using novel sample preparation, Low Energy Electron Diffraction (LEED) and other traditional ultra high vacuum (UHV) techniques are shown to provide new information on the insulator/vacuum interface. The surface structure of the classic insulator NaCl has been determined using these methods. Second, using sum frequency generation (SFG) surface specific vibrational spectroscopy studies were performed on both the biopolymer/air and electrode/electrolyte interfaces. The surface structure and composition of polyetherurethane-silicone copolymers were determined in air using SFG, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). SFG studies of the electrode (platinum, gold and copper)/electrolyte interface were performed as a function of applied potential in an electrochemical cell.

The Use of Linezolid in Children with Malignant Solid Tumors

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H.I. Klymniuk

2015-09-01

Full Text Available In recent decades, in the treatment of cancer there has been achieved a significant success not only by the introduction of cancer treatment protocol, but mostly due to the planned combination concomitant treatment of infectious complications. The need for antimicrobial agents against resistant Gram-positive bacteria, such as methicillin-resistant staphylococci, penicillin-resistant pneumococci, vancomycin-resistant enterococci, has significantly increased. In the department of pediatric oncology of the National cancer institute (Kyiv, linezolid preparations were used in children with infection of soft tissues and bones, febrile neutropenia and for the treatment of severe cases of sepsis. Experience of Linelid® use in the department of pediatric oncology of the National cancer institute indicates its effectiveness, safety and good tolerance in children with malignant solid tumors.

CAR T Cells Releasing IL-18 Convert to T-Bethigh FoxO1low Effectors that Exhibit Augmented Activity against Advanced Solid Tumors

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Markus Chmielewski

2017-12-01

Full Text Available Adoptive therapy with chimeric antigen receptor (CAR-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bethigh FoxO1low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines. IL-18 CAR T cell treatment was accompanied by an overall change in the immune cell landscape associated with the tumor. More specifically, CD206− M1 macrophages and NKG2D+ NK cells increased in number, whereas Tregs, suppressive CD103+ DCs, and M2 macrophages decreased, suggesting that “iIL18 TRUCKs” can be used to sensitize large solid tumor lesions for successful immune destruction.

Is the Spencer-Attix cavity equation applicable for solid-state detectors irradiated in megavoltage electron beams?

International Nuclear Information System (INIS)

Mobit, P.N.; Sandison, G.A.; Calgary Univ., AB

2001-01-01

The applicability of the Spencer-Attix cavity equation in determining absorbed doses in water using solid state detectors irradiated by megavoltage electron beams have been examined. The calculations were performed using the EGSnrc Monte Carlo code. This work is an extension of a recently published article examining the perturbation of dose by solid state detectors in megavoltage electron beams. (orig.)

Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

Science.gov (United States)

2018-05-15

Ewing's Sarcoma; Osteosarcoma; Astrocytoma; Atypical Teratoid/Rhabdoid Tumor; Ependymoma; Germ Cell Tumor; Glioma; Medulloblastoma; Rhabdoid Tumor; Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Rhabdomyosarcoma

Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

Science.gov (United States)

Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

2018-03-02

C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

Direct and Recoil-Induced Electron Emission from Ion-Bombarded Solids

DEFF Research Database (Denmark)

Holmen, G.; Svensson, B.; Schou, Jørgen

1979-01-01

The kinetic emission of secondary electrons from ion-bombarded solid surfaces is split into two contributions, a direct one caused by ionizing collisions between the bombarding ion and target atoms, and an indirect one originating from ionizing collisions undergone by recoil atoms with other target...... atoms. The direct contribution, which has been treated by several authors in previous studies, shows a behavior that is determined primarily by the electronic stopping power of the bombarding ion, while the indirect contribution is nonproportionally related to the nuclear stopping power. This latter...

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

Palliative Care Use Among Patients With Solid Cancer Tumors: A National Cancer Data Base Study.

Science.gov (United States)

Osagiede, Osayande; Colibaseanu, Dorin T; Spaulding, Aaron C; Frank, Ryan D; Merchea, Amit; Kelley, Scott R; Uitti, Ryan J; Ailawadhi, Sikander

2018-01-01

Palliative care has been increasingly recognized as an important part of cancer care but remains underutilized in patients with solid cancers. There is a current gap in knowledge regarding why palliative care is underutilized nationwide. To identify the factors associated with palliative care use among deceased patients with solid cancer tumors. Using the 2016 National Cancer Data Base, we identified deceased patients (2004-2013) with breast, colon, lung, melanoma, and prostate cancer. Data were described as percentages. Associations between palliative care use and patient, facility, and geographic characteristics were evaluated through multivariate logistic regression. A total of 1 840 111 patients were analyzed; 9.6% received palliative care. Palliative care use was higher in the following patient groups: survival >24 months (17% vs 2%), male (54% vs 46%), higher Charlson-Deyo comorbidity score (16% vs 8%), treatment at designated cancer programs (74% vs 71%), lung cancer (76% vs 28%), higher grade cancer (53% vs 24%), and stage IV cancer (59% vs 13%). Patients who lived in communities with a greater percentage of high school degrees had higher odds of receiving palliative care; Central and Pacific regions of the United States had lower odds of palliative care use than the East Coast. Patients with colon, melanoma, or prostate cancer had lower odds of palliative care than patients with breast cancer, whereas those with lung cancer had higher odds. Palliative care use in solid cancer tumors is variable, with a preference for patients with lung cancer, younger age, known insurance status, and higher educational level.

Directed Acceleration of Electrons from a Solid Surface by Sub-10-fs Laser Pulses

International Nuclear Information System (INIS)

Brandl, F.; Hidding, B.; Osterholz, J.; Hemmers, D.; Pretzler, G.; Karmakar, A.; Pukhov, A.

2009-01-01

Electrons have been accelerated from solid target surfaces by sub-10-fs laser pulses of 120 μJ energy which were focused to an intensity of 2x10 16 W/cm 2 . The electrons have a narrow angular distribution, and their observed energies exceed 150 keV. We show that these energies are not to be attributed to collective plasma effects but are mainly gained directly via repeated acceleration in the transient field pattern created by incident and reflected laser, alternating with phase-shift-generating scattering events in the solid.

Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors

DEFF Research Database (Denmark)

Sempere, Lorenzo F; Preis, Meir; Yezefski, Todd

2010-01-01

of altered miRNA expression in solid tumors, we developed a sensitive fluorescence-based in situ hybridization (ISH) method to visualize miRNA accumulation within individual cells in formalin-fixed, paraffin-embedded tissue specimens. This ISH method was implemented to be compatible with routine clinical...

PNU-145156E, a novel angiogenesis inhibitor, in patients with solid tumors : A phase I and pharmacokinetic study

NARCIS (Netherlands)

Groen, HJM; de Vries, EGE; Wynendaele, W; van der Graaf, WTA; Lechuga, EFMJ; Poggesi, [No Value; Dirix, LY; van Oosterom, AT

2001-01-01

Our aim was to establish, in patients with solid tumors, the dose-limiting toxicity, maximum tolerated dose (MTD), and pharmacology of PNU-145156E, a new sulfonated distamycin A derivative that blocked circulating angiogenesis-promoting growth factors in animal studies and exhibited an antitumor

Liver Tumors (For Parents)

Science.gov (United States)

... Staying Safe Videos for Educators Search English Español Liver Tumors KidsHealth / For Parents / Liver Tumors What's in this article? Types of Tumors ... Cancerous) Tumors Symptoms Diagnosis Treatment Coping Print The liver is the body's largest solid organ. Lying next ...

Radiation damage in nonmetallic solids under dense electronic excitation

International Nuclear Information System (INIS)

Itoh, Noriaki; Tanimura, Katsumi; Nakai, Yasuo

1992-01-01

Basic processes of radiation damage of insulators by dense electronic excitation are reviewed. First it is pointed out that electronic excitation of nonmetallic solids produces the self-trapped excitons and defect-related metastable states having relatively long lifetimes, and that the excitation of these metastable states, produces stable defects. The effects of irradiation with heavy ions, including track registration, are surveyed on the basis of the microscopic studies. It is pointed out also that the excitation of the metastable states plays a role in laser-induced damage at relatively low fluences, while the laser damage has been reported to be governed by heating of free electrons produced by multiphoton excitation. Difference in the contributions of the excitation of metastable defects to laser-induced damage of surfaces, or laser ablation, and laser-induced bulk damage is stressed. (orig.)

Pediatric brain tumors

Energy Technology Data Exchange (ETDEWEB)

Poussaint, Tina Y. [Department of Radiology, Boston, MA (United States); Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Huisman, Thierry A.G.M. [Charlotte R. Bloomberg Children' s Center, Johns Hopkins Hospital, Division of Pediatric Radiology and Pediatric Neuroradiology, Baltimore, MD (United States)

2015-09-15

Among all causes of death in children from solid tumors, pediatric brain tumors are the most common. This article includes an overview of a subset of infratentorial and supratentorial tumors with a focus on tumor imaging features and molecular advances and treatments of these tumors. Key to understanding the imaging features of brain tumors is a firm grasp of other disease processes that can mimic tumor on imaging. We also review imaging features of a common subset of tumor mimics. (orig.)

A Monte Carlo simulation code for calculating damage and particle transport in solids: The case for electron-bombarded solids for electron energies up to 900 MeV

Energy Technology Data Exchange (ETDEWEB)

Yan, Qiang [College of Nuclear Science and Technology, Harbin Engineering University, Harbin 150001 (China); Shao, Lin, E-mail: lshao@tamu.edu [Department of Nuclear Engineering, Texas A& M University, College Station, TX 77843 (United States)

2017-03-15

Current popular Monte Carlo simulation codes for simulating electron bombardment in solids focus primarily on electron trajectories, instead of electron-induced displacements. Here we report a Monte Carol simulation code, DEEPER (damage creation and particle transport in matter), developed for calculating 3-D distributions of displacements produced by electrons of incident energies up to 900 MeV. Electron elastic scattering is calculated by using full-Mott cross sections for high accuracy, and primary-knock-on-atoms (PKAs)-induced damage cascades are modeled using ZBL potential. We compare and show large differences in 3-D distributions of displacements and electrons in electron-irradiated Fe. The distributions of total displacements are similar to that of PKAs at low electron energies. But they are substantially different for higher energy electrons due to the shifting of PKA energy spectra towards higher energies. The study is important to evaluate electron-induced radiation damage, for the applications using high flux electron beams to intentionally introduce defects and using an electron analysis beam for microstructural characterization of nuclear materials.

Fast-electron-relaxation measurement for laser-solid interaction at relativistic laser intensities

International Nuclear Information System (INIS)

Chen, H.; Shepherd, R.; Chung, H. K.; Kemp, A.; Hansen, S. B.; Wilks, S. C.; Ping, Y.; Widmann, K.; Fournier, K. B.; Beiersdorfer, P.; Dyer, G.; Faenov, A.; Pikuz, T.

2007-01-01

We present measurements of the fast-electron-relaxation time in short-pulse (0.5 ps) laser-solid interactions for laser intensities of 10 17 , 10 18 , and 10 19 W/cm 2 , using a picosecond time-resolved x-ray spectrometer and a time-integrated electron spectrometer. We find that the laser coupling to hot electrons increases as the laser intensity becomes relativistic, and that the thermalization of fast electrons occurs over time scales on the order of 10 ps at all laser intensities. The experimental data are analyzed using a combination of models that include Kα generation, collisional coupling, and plasma expansion

Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice

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Shoya Shiromizu

2018-04-01

Full Text Available Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Keywords: l-asparaginase, Asparagine, Solid tumor, Chrono-pharmacotherapy

A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

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Han LQ

2016-11-01

Full Text Available Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, Shandong, People’s Republic of China Abstract: Small molecule-based nanodrugs with nanoparticles (NPs that are mainly composed of small molecules, have been considered as a promising candidate for a next-generation nanodrug, owing to their unique properties. Vorinostat (SAHA is a canonical US Food and Drug Administration-approved histone deacetylase (HDAC inhibitor for the treatment of cutaneous T-cell lymphoma. However, the lack of efficacy against solid tumors hinders its progress in clinical use. Herein, a novel nanodrug of SAHA was developed based on disulfide-linked prodrug SAHA-S-S-VE. SAHA-S-S-VE could self-assemble into 148 nm NPs by disulfide-induced mechanisms, which were validated by molecular dynamics simulations. Under reduced conditions, the redox-responsive behavior of SAHA-S-S-VE was investigated, and the HDAC inhibition results verified the efficient release of free SAHA. With a biocompatible d-a-tocopheryl polyethylene glycol succinate (TPGS functionalization, the SAHA-S-S-VE/TPGS NPs exhibited low critical aggregation concentration of 4.5 µM and outstanding stability in vitro with drug-loading capacity of 24%. In vitro biological assessment indicated that SAHA-S-S-VE/TPGS NPs had significant anticancer activity against HepG2. Further in vivo evaluation demonstrated that the resulting NPs could be accumulated in the tumor region and inhibit the tumor growth effectively. This approach, which turned SAHA into a self-assembled redox-responsive nanodrug, provided a new channel for the use of HDAC inhibitor in solid tumor therapy. Keywords: SAHA, HDAC, small molecule, nanoparticles, self-assemble, disulfide bond

A universal equation for the electronic stopping of ions in solids

International Nuclear Information System (INIS)

Montenegro, E.C.; Cruz, S.A.; Vargas-Aburto, C.

1982-09-01

An analytical equation for the electronic stopping of ions in solids for non-relativistic velocities, that has no adjustable parameters, is obtained in a semi-phenomenological manner. The very good agreement with experiment gives support to the physical arguments used in its derivation. (Author) [pt

The occurrence of recruitment supported from the finding of an increase in radiosensitivity of quiescent cells in solid tumors after fractionated irradiation with X-rays

International Nuclear Information System (INIS)

Masunaga, Shinichiro; Ono, Koji; Kinashi, Yuko; Suzuki, Minoru; Akaboshi, Mitsuhiko

1998-01-01

We examined the behavior of quiescent cells in solid tumors irradiated twice at various intervals with X-rays, using our recently developed method for selectively detecting the response of quiescent cells in solid tumors. To determine the labeling indices of tumors at the second irradiation, each mouse group included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted before the first irradiation. Radiosensitivity of total tumor cells at the second irradiation decreased in proportion to the increase in interval time. However, radiosensitivity of quiescent cells was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings supported the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation. (author)

Escaping Electrons from Intense Laser-Solid Interactions as a Function of Laser Spot Size

OpenAIRE

Rusby, Dean; Gray, Ross; Butler, Nick; Dance, Rachel; Scott, Graeme; Bagnoud, Vincent; Zielbauer, Bernhard; McKenna, Paul; Neely, David

2018-01-01

The interaction of a high-intensity laser with a solid target produces an energetic distribution of electrons that pass into the target. These electrons reach the rear surface of the target creating strong electric potentials that act to restrict the further escape of additional electrons. The measurement of the angle, flux and spectra of the electrons that do escape gives insights to the initial interaction. Here, the escaping electrons have been measured using a differentially filtered imag...

A novel gene therapy-based approach that selectively targets hypoxic regions within solid tumors

International Nuclear Information System (INIS)

Dougherty, S.T.; Dougherty, G.J.; Davis, P.D.

2003-01-01

There is compelling evidence that malignant cells present within the hypoxic regions that are commonly found within solid tumors contribute significantly to local recurrence following radiation therapy. We describe now a novel strategy designed to target such cells that exploits the differential production within hypoxic regions of the pro-angiogenic cytokine vascular endothelial cell growth factor (VEGF). Specifically, we have generated cDNA constructs that encode two distinct chimeric cell surface proteins that incorporate, respectively, the extracellular domains of the VEGF receptors Flk-1 or Flt-1, fused in frame to the membrane spanning and cytoplasmic domains of the pro-apoptotic protein Fas. Both chimeric proteins (Flk/Fas and Flt/Fas) appear stable and can be readily detected on the surface of transfected cells by Western blot and/or FACS analysis. Importantly, tumor cells expressing the chimeric proteins were rapidly killed in a dose-dependent fashion upon the addition of exogenous recombinant VEGF. Adenoviral vectors encoding Flk/Fas have been generated and shown to induce tumor cells to undergo apoptosis upon transfer to hypoxic conditions in vitro. This activity is dependent upon the endogenous production of VEGF. Studies are currently underway to test the ability of adenoviral Flk/Fas (Ad.Flk/Fas) to reduce tumor recurrence in vivo when used as an adjuvant therapy in conjunction with clinically relevant doses of ionizing radiation

A multislice theory of electron inelastic scattering in a solid

International Nuclear Information System (INIS)

Wang, Z.L.

1989-01-01

A multislice theory is proposed to solve Yoshioka's coupling equations for elastic and inelastic scattered high-energy electrons in a solid. This method is capable, in principle, of including the non-periodic crystal structures and the electron multiple scattering among all the excited states in the calculations. It is proved that the proposed theory for calculating the energy-filtered inelastic images, based on the physical optics approach, is equivalent to the quantum-mechanical theory under some approximations. The basic theory of simulating the energy-filtered inelastic image of core-shell losses and thermal diffuse scattering is outlined. (orig.)

Theoretical solid state physics

CERN Document Server

Haug, Albert

2013-01-01

Theoretical Solid State Physics, Volume 1 focuses on the study of solid state physics. The volume first takes a look at the basic concepts and structures of solid state physics, including potential energies of solids, concept and classification of solids, and crystal structure. The book then explains single-electron approximation wherein the methods for calculating energy bands; electron in the field of crystal atoms; laws of motion of the electrons in solids; and electron statistics are discussed. The text describes general forms of solutions and relationships, including collective electron i

Theoretical study of the transmission of low-energy (0-10 eV) electrons through thin-film organic molecular solids: benzene

International Nuclear Information System (INIS)

Goulet, T.; Jay-Gerin, J.-P.

1986-01-01

A theoretical study of the transmission of low-energy (0 to 10 eV) electrons incident from vacuum through thin-film organic molecular solids deposited on a cold metal substrate is presented and developed for the specific case of solid benzene. In essence, using a semiclassical description of electron transport in solids with an energy-independent scattering mean free path and assuming an isotropic electron scattering, the behavior of a penetrating electron in the film is simulated when a large number of scattering events are present. The good agreement between the calculated electron transmission spectra and those obtained experimentally indicates that our study provides a realistic description of the electron transport in the film, and accounts for the influence of the various electron-molecule scattering processes upon the energy dependence of the transmitted current. In particular, we show that the excitonic subionization energy losses are at the origin of the main structures of the observed electron transmission spectra. It is also shown that our study can successfully be used to estimate the probabilities of the various electron scattering processes which occur in the film, as well as the electron mean free path (l). For solid benzene, l is about 8 A in the considered electron energy range. (author)

Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model

International Nuclear Information System (INIS)

Nagane, Masaki; Yasui, Hironobu; Yamamori, Tohru; Zhao, Songji; Kuge, Yuji; Tamaki, Nagara; Kameya, Hiromi; Nakamura, Hideo; Fujii, Hirotada; Inanami, Osamu

2013-01-01

Highlights: •IR-induced NO increased tissue perfusion and pO 2 . •IR increased NO production in tumors without changes in the mRNA and protein levels of NOS isoforms. •NOS activity assay showed that IR upregulated eNOS activity in tumors. •IR-induced NO decreased tumor hypoxia and altered tumor radiosensitivity. -- Abstract: Tumor hypoxia, which occurs mainly as a result of inadequate tissue perfusion in solid tumors, is a well-known challenge for successful radiotherapy. Recent evidence suggests that ionizing radiation (IR) upregulates nitric oxide (NO) production and that IR-induced NO has the potential to increase intratumoral circulation. However, the kinetics of NO production and the responsible isoforms for NO synthase in tumors exposed to IR remain unclear. In this study, we aimed to elucidate the mechanism by which IR stimulates NO production in tumors and the effect of IR-induced NO on tumor radiosensitivity. Hoechst33342 perfusion assay and electron spin resonance oxymetry showed that IR increased tissue perfusion and pO 2 in tumor tissue. Immunohistochemical analysis using two different hypoxic probes showed that IR decreased hypoxic regions in tumors; treatment with a nitric oxide synthase (NOS) inhibitor, L-NAME, abrogated the effects of IR. Moreover, IR increased endothelial NOS (eNOS) activity without affecting its mRNA or protein expression levels in SCCVII-transplanted tumors. Tumor growth delay assay showed that L-NAME decreased the anti-tumor effect of fractionated radiation (10 Gy × 2). These results suggested that IR increased eNOS activity and subsequent tissue perfusion in tumors. Increases in intratumoral circulation simultaneously decreased tumor hypoxia. As a result, IR-induced NO increased tumor radiosensitivity. Our study provides a new insight into the NO-dependent mechanism for efficient fractionated radiotherapy

Using Electronic Noses to Detect Tumors During Neurosurgery

Science.gov (United States)

Homer, Margie L.; Ryan, Margaret A.; Lara, Liana M.; Kateb, Babak; Chen, Mike

2008-01-01

It has been proposed to develop special-purpose electronic noses and algorithms for processing the digitized outputs of the electronic noses for determining whether tissue exposed during neurosurgery is cancerous. At present, visual inspection by a surgeon is the only available intraoperative technique for detecting cancerous tissue. Implementation of the proposal would help to satisfy a desire, expressed by some neurosurgeons, for an intraoperative technique for determining whether all of a brain tumor has been removed. The electronic-nose technique could complement multimodal imaging techniques, which have also been proposed as means of detecting cancerous tissue. There are also other potential applications of the electronic-nose technique in general diagnosis of abnormal tissue. In preliminary experiments performed to assess the viability of the proposal, the problem of distinguishing between different types of cultured cells was substituted for the problem of distinguishing between normal and abnormal specimens of the same type of tissue. The figure presents data from one experiment, illustrating differences between patterns that could be used to distinguish between two types of cultured cancer cells. Further development can be expected to include studies directed toward answering questions concerning not only the possibility of distinguishing among various types of normal and abnormal tissue but also distinguishing between tissues of interest and other odorous substances that may be present in medical settings.

Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

Science.gov (United States)

Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

2015-10-13

Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

Directory of Open Access Journals (Sweden)

Andrea eGras Navarro

2015-04-01

Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

Computed tomographic findings of ovarian tumors

Energy Technology Data Exchange (ETDEWEB)

Kwon, Kwi Ryeon; Lee, Ki Man; Woo, Seong Ku; Suh, Soo Jhi [Keimyung University School of Medicine, Seoul (Korea, Republic of); Kang, Duk Sik [Kyungpook National University College of Medicine, Taegu (Korea, Republic of)

1986-08-15

The diagnosis of ovarian tumor has been mainly dependent on manual pelvic examination and ultrasonography. But in case of malignant ovarian tumor, CT has more advantages over ultrasonography in assessing anatomic details, relationships to bowel loops, precise extents of tumors and follow-up examinations after surgery. Authors analyzed CT features of 46 cases of pathologically proven ovarian tumors for recent 4 years at Keimyung University Dongsan Hospital. The results were as follows: 1. The most common tumor was serous cyst adenocarcinoma (9 cases: 20%), followed by metastases (8 cases: 17%), mucinous cyst adenocarcinoma (7 cases: 15%), mucinous cyst adenocarcinoma (5 cases: 11%), teratoma (5 cases: 11%), lymphoma (3 cases: 7%) and dysgerminoma (2 cases: 4%). 2. The ovarian tumors were variable in size from 2.5 cm to 33 cm in diameter. Most of the solid tumors were smaller than 10 cm in diameter and most of the cystic tumors were larger than 10 cm in diameter. Usually mucinous tumors were much larger than serous tumors. Mucinous cyst adenomas were the largest tumors. 3. Unilateral tumors (left 19, right 13 cases) were more common than bilateral tumors (12 cases). Bilateral tumors were seen in serous and mucinous cyst adenocarcinoma, metastases and lymphoma. 4. CT features of mucinous cyst adenomas were smooth margins and thin wall of the tumor masses and multifaceted cysts with internal septa in all 7 cases. 5. In contrast, CT demonstration of bilaterally, irregular margin, thick wall, enhancing solid lesion, septal irregularity, adhesion to adjacent structures, peritoneal/omental implantation, ascites and hydronephrosis were signs suggesting malignancy. CT features of the serous cyst adenocarcinoma were mostly solid to mixed nature (83%), irregular margin (75%), enhancing solid lesion (67%), papillary growth (75%), internal septa (58%), multilocularity (58%) and calcification (25%) in descending order of frequency. 6. On CT, mucinous cystadenocarcinoma were

NATO Advanced Study Institute on Relativistic and Electron Correlation Effects in Molecules and Solids

CERN Document Server

1994-01-01

The NATO Advanced Study Institute (ASI) on "R@lativistic and Electron Correlation Effects in Molecules and Solids", co-sponsored by Simon Fraser University (SFU) and the Natural Sciences and Engineering Research Council of Canada (NSERC) was held Aug 10- 21, 1992 at the University of British Columbia (UBC), Vancouver, Canada. A total of 90 lecturers and students with backgrounds in Chemistry, Physics, Mathematics and various interdisciplinary subjects attended the ASI. In my proposal submitted to NATO for financial support for this ASI, I pointed out that a NATO ASI on the effects of relativity in many-electron systems was held ten years ago, [See G.L. Malli, (ed) Relativistic Effects in Atoms, Molecules and Solids, Plenum Press, Vol B87, New York, 1983]. Moreover, at a NATO Advanced Research Workshop (ARW) on advanced methods for molecular electronic structure "an assessment of state-of­ the-art of Electron Correlation ... " was carried out [see C.E. Dykstra, (ed), Advanced Theories and Computational Approa...

BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

Directory of Open Access Journals (Sweden)

Cohn AL

2017-02-01

Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

Electron probe micro-analysis of gas bubbles in solids: a novel approach

International Nuclear Information System (INIS)

Verwerft, M.; Vos, B.

1999-01-01

The local analysis of retained noble gas in nuclear fuel is inherently difficult since the physical form under which it is stored varies from atomically dispersed to bubbles with a diameter of several hundreds of nanometers. One of the techniques that has been applied since pore than twenty years is EPMA. Although many important results have been obtained with this technique, its application to the analysis of highly inhomogeneous materials is limited. The EPMA technique is indeed difficult to apply to samples that are not homogeneous on the scale of the electron-solid interaction volume. The paper discusses the development of a method to analyse a system of as bubbles distributed in a solid matrix. This method has been based on a multiple voltage EPMA measurement combined with a scanning Electron Microscopic analysis of the bubble size distribution

In Vivo pO2 Imaging of Tumors: Oxymetry with Very Low-Frequency Electron Paramagnetic Resonance.

Science.gov (United States)

Epel, Boris; Halpern, Howard J

2015-01-01

For over a century, it has been known that tumor hypoxia, regions of a tumor with low levels of oxygenation, are important contributors to tumor resistance to radiation therapy and failure of radiation treatment of cancer. Recently, using novel pulse electron paramagnetic resonance (EPR) oxygen imaging, near absolute images of the partial pressure of oxygen (pO2) in tumors of living animals have been obtained. We discuss here the means by which EPR signals can be obtained in living tissues and tumors. We review development of EPR methods to image the pO2 in tumors and the potential for the pO2 image acquisition in human subjects. © 2015 Elsevier Inc. All rights reserved.

In vivo pO2 imaging of tumors: Oxymetry with very low frequency Electron Paramagnetic Resonance

Science.gov (United States)

Epel, Boris; Halpern, Howard J.

2016-01-01

For over a century it has been known that tumor hypoxia, regions of a tumor with low levels of oxygenation, are important contributors to tumor resistance to radiation therapy and failure of radiation treatment of cancer. Recently, using novel pulse electron paramagnetic resonance (EPR) oxygen imaging, near absolute images of the partial pressure of oxygen (pO2) in tumors of living animals have been obtained. We discuss here the means by which EPR signals can be obtained in living tissues and tumors. We review development of EPR methods to image the pO2 in tumors and the potential for the pO2 image acquisition in human subjects. PMID:26477263

Applications of lipid nanocarriers for solid tumors therapy: literature review; Aplicacoes das nanoparticulas lipidicas no tratamento de tumores solidos: revisao de literatura

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Fac. de Farmacia; Taveira, Eliseu Jose Fleury, E-mail: stephaniafleury@gmail.com [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Oncologia Clinica

2012-07-01

Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed{sup R} database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

PET/CT evaluation of response to chemotherapy in non-small cell lung cancer: PET response criteria in solid tumors (PERCIST) versus response evaluation criteria in solid tumors (RECIST).

Science.gov (United States)

Ding, Qiyong; Cheng, Xu; Yang, Lu; Zhang, Qingbo; Chen, Jianwei; Li, Tiannv; Shi, Haibin

2014-06-01

(18)F-FDG PET/CT is increasingly used in evaluation of treatment response for patients with non-small cell lung cancer (NSCLC). There is a need for an accurate criterion to evaluate the effect and predict the prognosis. The aim of this study is to evaluate therapeutic response in NSCLC with comparing PET response criteria in solid tumors (PERCIST) to response evaluation criteria in solid tumors (RECIST) criteria on PET/CT. Forty-four NSCLC patients who received chemotherapy but no surgery were studied. Chemotherapeutic responses were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST methodologies. PET/CT scans were obtained before chemotherapy and after 2 or 4-6 cycles' chemotherapy. The percentage changes of tumor longest diameters and standardized uptake value (SUV) (corrected for lean body mass, SUL) before and after treatment were compared using paired t-test. The response was categorized into 4 levels according to RECIST and PERCIST: CR (CMR) =1, PR (PMR) =2, SD (SMD) =3, PD (PMD) =4. Pearson chi-square test was used to compare the proportion of four levels in RECIST and PERCIST. Finally the relationship between progression-free survival (PFS) and clinicopathologic parameters (such as TNM staging, percentage changes in diameters and SUL, RECIST and PERCIST results etc.) were evaluated using univariate and multivariate Cox proportional hazards regression method. The difference of percentage changes between diameters and SUL was not significant using paired t-test (t=-1.69, P=0.098). However the difference was statistically significant in the 40 cases without increasing SUL (t=-3.31, P=0.002). The difference of evaluation results between RECIST and PERCIST was not significant by chi-square test (χ(2)=5.008, P=0.171). If RECIST evaluation excluded the new lesions which could not be found or identified on CT images the difference between RECIST and PERCIST was significant (χ(2)=11.759, P=0.007). Reduction rate of SULpeak (%), RECIST and

Development of cell-cycle checkpoint therapy for solid tumors.

Science.gov (United States)

Tamura, Kenji

2015-12-01

Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

International Nuclear Information System (INIS)

Rossi, Sabrina; Toschi, Luca; Castello, Angelo; Grizzi, Fabio; Mansi, Luigi; Lopci, Egesta

2017-01-01

The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging

Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

Energy Technology Data Exchange (ETDEWEB)

Rossi, Sabrina; Toschi, Luca [Humanitas Clinical and Research Hospital, Medical Oncology, Rozzano (Italy); Castello, Angelo [Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano (Italy); Grizzi, Fabio [Humanitas Clinical and Research Hospital, Immunology and Inflammation, Rozzano (Italy); Mansi, Luigi [Seconda Universita di Napoli, Nuclear Medicine, Naples (Italy); Lopci, Egesta [Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano (Italy); Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano, MI (Italy)

2017-12-15

The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging

Electron beam produced in a transient hollow cathode discharge: beam electron distribution function, X-ray emission and solid target ablation

International Nuclear Information System (INIS)

Nistor, Magdalena

2000-01-01

This research thesis aims at a better knowledge of phenomena occurring during transient hollow cathode discharges. The author first recalls the characteristics of such a discharge which make it different from conventional pseudo-spark discharges. The objective is to characterise the electron beam produced within the discharge, and the phenomena associated with its interaction with a solid or gaseous target, leading to the production of an X ray or visible radiation. Thus, the author reports the measurement (by magnetic deflection) of the whole time-averaged electronic distribution function. Such a knowledge is essential for a better use of the electron beam in applications such as X-ray source or material ablation. As high repetition frequency pulse X ray sources are very interesting tools, he reports the development and characterisation of Bremsstrahlung X rays during a beam-target interaction. He finally addresses the implementation of a spectroscopic diagnosis for the filamentary plasma and the ablation of a solid target by the beam [fr

Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

Directory of Open Access Journals (Sweden)

Hamid R Molavian

Full Text Available Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997 provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2 are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2 and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.

Radiobiologic significance of apoptosis and micronucleation in quiescent cells within solid tumors following γ-ray irradiation

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Kinashi, Yuko; Takagaki, Masao

2001-01-01

Purpose: To determine the frequency of apoptosis in quiescent (Q) cells within solid tumors following γ-ray irradiation, using four different tumor cell lines. In addition, to assess the significance of detecting apoptosis in these cell lines. Methods and Materials: C3H/He mice bearing SCC VII or FM3A tumors, Balb/c mice bearing EMT6/KU tumors, and C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received γ-ray irradiation at a dose of 4-25 Gy while alive or after tumor clamping. Immediately after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same manner were fixed. The apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: In total cells, SCC VII, FM3A, and EMT6/KU cells showed reasonable relationships between MN frequency and surviving fraction (SF). However, fewer micronuclei were induced in EL4 cells than the other cell lines. In contrast, a comparatively close relationship between apoptosis frequency and SF was found in total cells of EL4 cell line. Less apoptosis was observed in the other cell lines. Quiescent tumor cells exhibited significantly lower values of MN and apoptosis frequency probably due to their large hypoxic fraction, similar to total tumor cells on clamped irradiation. Conclusion: γ-ray irradiation induced MN formation in SCC VII, FM3A, and EMT6/KU tumor cells, and the apoptosis was marked in EL4 cells compared with

Electron beam absorption in solid and in water phantoms: depth scaling and energy-range relations

International Nuclear Information System (INIS)

Grosswendt, B.; Roos, M.

1989-01-01

In electron dosimetry energy parameters are used with values evaluated from ranges in water. The electron ranges in water may be deduced from ranges measured in solid phantoms. Several procedures recommended by national and international organisations differ both in the scaling of the ranges and in the energy-range relations for water. Using the Monte Carlo method the application of different procedures for electron energies below 10 MeV is studied for different phantom materials. It is shown that deviations in the range scaling and in the energy-range relations for water may accumulate to give energy errors of several per cent. In consequence energy-range relations are deduced for several solid phantom materials which enable a single-step energy determination. (author)

Sputtering of thin and intermediately thick films of solid deuterium by keV electrons

DEFF Research Database (Denmark)

Svendsen, Winnie Edith; Thestrup Nielsen, Birgitte; Schou, Jørgen

1995-01-01

Sputtering of films of solid deuterium by keV electrons was studied in a cryogenic set-up. The sputtering yield shows a minimum yield of about 4 D2/electron for 1.5 and 2 keV electrons at a thickness slightly larger than the average projected range of the electrons. We suggest that the yield around...... the minimum represents the value closest to a bulk-yield induced by electron bombardment. It may also include contributions from the mechanisms that enhance the yield for thin and very thick films....

Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

International Nuclear Information System (INIS)

Mamuris, Z.; Dumont, J.; Dutrillaux, B.; Aurias, A.

1989-01-01

A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients

CT of abdominal tumor

International Nuclear Information System (INIS)

Endo, Satoshi; Yamada, Kenji; Ito, Masatoshi; Ito, Hisao; Yamaura, Harutsugu

1981-01-01

CT findings in 33 patients who had an abdominal tumor were evaluated. CT revealed a tumor in 31 cases. The organ from which the tumor originated was correctly diagnosed in 18 patients. Whether the tumor was solid or cystic was correctly predicted in 28 patients. The diagnosis malignant or benign nature of tumor was correct, incorrect and impossible, in 23, 3, and five patiens, respectively. (Kondo, M.)

Marcadores de proliferação celular na avaliação do crescimento do tumor sólido e ascítico de Ehrlich Cell proliferation markers for evaluating the growth of solid and ascitic forms of Ehrlich tumor

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A.E. Silva

2006-08-01

Full Text Available Twenty BALB/c mice were inoculated with cell suspension of Ehrlich tumor. Ten mice were inoculated in the cushion plant (solid form and the other 10 in the peritoneum (ascitic form. Animals were euthanized on different times (7 and 14 days. Cytological and histological slides, immunohistochemical (PCNA analysis and NORs silver impregnation technique were performed. The results showed more proliferation on the 7th day in the ascitic form and on 14th day in the solid form, using both analyses (PCNA and AgNORs. The alterations observed in the Ehrlich tumor’s proliferation activity suggested that the growth curve is different between ascitic and solid forms. In the first one, the proliferation peak occurs on the seventh day and in the solid tumor the growth curve was more delayed, showing increased proliferative potential after seven days.

Solid-State Photomultiplier with Integrated Front End Electronics

Science.gov (United States)

Christian, James; Stapels, Christopher; Johnson, Erik; Mukhopadhyay, Sharmistha; Jie Chen, Xiao; Miskimen, Rory

2009-10-01

The instrumentation cost of physics experiments has been reduced per channel, by the use of solid-state detectors, but these cost-effective techniques have not been translated to scintillation-based detectors. When considering photodetectors, the cost per channel is determined by the use of high-voltage, analog-to-digital converters, BNC cables, and any other ancillary devices. The overhead associated with device operation limits the number of channels for the detector system, while potentially limiting the scope of physics that can be explored. The PRIMEX experiment at JLab, which is being designed to measure the radiative widths of the η and η' pseudo-scalar mesons for a more comprehensive understanding of QCD at low energies, is an example where CMOS solid-state photomultipliers (SSPMs) can be implemented. The ubiquitous nature of CMOS allows for on-chip signal processing to provide front-end electronics within the detector package. We present the results of the device development for the PRIMEX calorimeter, discussing the characteristics of SSPMs, the potential cost savings, and experimental results of on-chip signal processing.

Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. Introduction of a multiinstitutional research project

International Nuclear Information System (INIS)

Zips, D.; Petersen, C.; Adam, M.; Molls, M.; Philbrook, C.; Flentje, M.; Haase, A.; Schmitt, P.; Mueller-Klieser, W.; Thews, O.; Walenta, S.; Baumann, M.

2004-01-01

Background: recent developments in imaging technology and tumor biology have led to new techniques to detect hypoxia and related alterations of the metabolic microenvironment in tumors. However, whether these new methods can predict radiobiological hypoxia and outcome after fractionated radiotherapy still awaits experimental evaluation. Material and methods: the present article will introduce a multiinstitutional research project addressing the impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. The four laboratories involved are situated at the universities of Dresden, Mainz, Munich and Wuerzburg, Germany. Results: the joint scientific project started to collect data obtained on a set of ten different human tumor xenografts growing in nude mice by applying various imaging techniques to detect tumor hypoxia and related parameters of the metabolic microenvironment. These techniques include magnetic resonance imaging and spectroscopy, metabolic mapping with quantitative bioluminescence and single-photon imaging, histological multiparameter analysis of biochemical hypoxia, perfusion and vasculature, and immunohistochemistry of factors related to angiogenesis, invasion and metastasis. To evaluate the different methods, baseline functional radiobiological data including radiobiological hypoxic fraction and outcome after fractionated irradiation will be determined. Conclusion: besides increasing our understanding of tumor biology, the project will focus on new, clinically applicable strategies for microenvironment profiling and will help to identify those patients that might benefit from targeted interventions to improve tumor oxygenation. (orig.)

Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications

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George D. Cresswell

2016-07-01

Full Text Available The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT; current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution.

Targeted drug delivery and penetration into solid tumors.

Science.gov (United States)

Corti, Angelo; Pastorino, Fabio; Curnis, Flavio; Arap, Wadih; Ponzoni, Mirco; Pasqualini, Renata

2012-09-01

Delivery and penetration of chemotherapeutic drugs into tumors are limited by a number of factors related to abnormal vasculature and altered stroma composition in neoplastic tissues. Coupling of chemotherapeutic drugs with tumor vasculature-homing peptides or administration of drugs in combination with biological agents that affect the integrity of the endothelial lining of tumor vasculature is an appealing strategy to improve drug delivery to tumor cells. Promising approaches to achieve this goal are based on the use of Asn-Gly-Arg (NGR)-containing peptides as ligands for drug delivery and of NGR-TNF, a peptide-tumor necrosis factor-α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma. © 2011 Wiley Periodicals, Inc.

CCCT - NCTN Steering Committees - Pediatric and Adolescent Tumor

Science.gov (United States)

The Pediatric and Adolescent Solid Tumor Steering Committee addresses the design, prioritization and evaluation of concepts for large phase 2 and phase 3 clinical trials in extracranial solid tumors of children and youth.

Projectile- and charge-state-dependent electron yields from ion penetration of solids as a probe of preequilibrium stopping power

DEFF Research Database (Denmark)

Rothard, H.; Schou, Jørgen; Groeneveld, K.-O.

1992-01-01

Kinetic electron-emission yields gamma from swift ion penetration of solids are proportional to the (electronic) stopping power gamma approximately Beta-S*, if the preequilibrium evolution of the charge and excitation states of the positively charged ions is taken into account. We show...... by investigating the "transport factor" beta, the energy spectrum of directly ejected recoil electrons and the evolution of ionic charge state inside solids. Estimates of the energy-loss fraction leading to electron emission and the effective charges of the ions near the surface allow a quantitative description...

Electron, ion and atomic beams interaction with solid high-molecular dielectrics

Energy Technology Data Exchange (ETDEWEB)

Milyavskij, V V; Skvortsov, V A [Russian Academy of Sciences, Moscow (Russian Federation). High Energy Density Research Center

1997-12-31

A mathematical model was constructed and numerical investigation performed of the interaction between intense electron, ion and atomic beams and solid high-molecular dielectrics under various boundary conditions. The model is based on equations of the mechanics of continuum, electrodynamics and kinetics, describing the accumulation and relaxation of space charge and shock-wave processes, as well as the evolution of electric field in the sample. A semi-empirical procedure is proposed for the calculation of energy deposition by electron beam in a target in the presence of a non-uniform electric field. (author). 4 figs., 2 refs.

Long-Range Electron Effects upon Irradiation of Molecular Solids and Polymers

International Nuclear Information System (INIS)

Feldman, V.I.

2006-01-01

Long-range electron effects are responsible for specific localization and selectivity of the radiation-induced chemical transformations occurring in molecular solids and polymers, when the classic diffusion mobility is essentially restricted. In particullar, understanding of the effects of this kind may be of key significance for establishing new ways to control the radiation sensitivity of macromolecules and organized polymeric systems, nanomaterials and biopolymers. This talk will present an overview of model studies of the long-range electron effects with the characteristic scale from several angstroms to ten nanometers. The following aspects of the problem will be analyzed: (1) Positive hole delocalization in ionized molecules. This phenomenon has been demonstrated experimentally and confirmed by quantum chemical calculations for a number of various-type molecules (alkanes, conjugated polyenes, bifunctional compounds). The effective delocalization length was found to be up to 2 nm (or even larger). The role of this effect in site-selective radiation chemistry will be discussed in the frame of concepts of distributed reactivity and 'switching' between delocalized and localized states. (2) Trap-to-trap positive hole and electron migration between isolated molecules or functional groups. The characteristic distance for this process was estimated to be 2 to 4 nm. Special impact will be made on the possible role of this process in selection of specific isomers or conformers upon irradiation of complex systems and macromolecules. (3) The effects of long-range scavenging of low-energy secondary electrons in polymers and organized polymeric systems. As revealed by model experiments, the radius of electron capture in solid polymers may be in the range of 1 to 10 nm. Possible implications of scavenging effects for controlling the radiation chemistry of polymers and organized polymeric systems will be considered

Effect of veliparib (ABT-888) on cardiac repolarization in patients with advanced solid tumors : a randomized, placebo-controlled crossover study

NARCIS (Netherlands)

Munasinghe, Wijith; Stodtmann, Sven; Tolcher, Anthony; Calvo, Emiliano; Gordon, Michael; Jalving, Mathilde; de Vos-Geelen, Judith; Medina, Diane; Bergau, Dennis; Nuthalapati, Silpa; Hoffman, David; Shepherd, Stacie; Xiong, Hao

2016-01-01

Veliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the effect of veliparib on corrected QT interval using Fridericia's formula (QTcF). Eligible patients with advanced solid tumors received single-dose oral

A conceptual design of the set-up for solid state spectroscopy with free electron laser and insertion device radiation

CERN Document Server

Makhov, V N

2001-01-01

The set-up for complex solid state spectroscopy with the use of enhanced properties of radiation from insertion devices and free electron lasers is proposed. Very high flux and pulsed properties of radiation from insertion devices and free electron lasers offer the possibility for the use of such powerful techniques as electron paramagnetic resonance (EPR) and optically detected magnetic resonance (ODMR) for the studies of excited states of electronic excitations or defects in solids. The power density of radiation can become high enough for one more method of exited-state spectroscopy: transient optical absorption spectroscopy. The set-up is supposed to combine the EPR/ODMR spectrometer, i.e. cryostat supplied with superconducting magnet and microwave system, and the optical channels for excitation (by radiation from insertion devices or free electron laser) and detection of luminescence (i.e. primary and secondary monochromators). The set-up can be used both for 'conventional' spectroscopy of solids (reflec...

Radiologic findings of granulosa cell tumor of the ovary

Energy Technology Data Exchange (ETDEWEB)

Sohn, Jung Eun; Kim, Kie Hwan; Yoo, Ji Young; Lee, Eun Chun; Lee, Tae Hyun; Chin, Soo Il [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1997-08-01

To evaluate the radiologic findings of granulosa cell tumor of the ovary. Fourteen cases(fifteen tumors) of pathologically confirmed ovarian granulosa cell tumor were retrospectively analyzed on the basis of CT(n=10), MR imaging(n=4), and ultrasound(n=7) findings. The patients' mean age was 44.3(range, 5-71)years. The mean diameter of the tumors was 12.1(range, 5-26.5)cm. Thirteen cases were unilateral, and one was bilateral. Eleven tumors(ten cases) were mainly solid and eight of these had focal cystic components. Multilocular cysts accounted for three cases, and in two of these, mural nodules were present. One case was a unilocular cyst with no mural nodule. Ten cases were well demarcated. All the solid tumors were enhanced on postcontrast CT and MR imaging. Endometrial thickening was seen in five cases, ascites in six, and peritoneal implants or omental fat infiltration in five. One was associated with lymph node metastasis. All the postmenopausal patients had solid tumors, whereas 66.7%(4 of 6 cases) of young adults and children had cystic tumors. Granulosa cell tumors of the ovary were solid or cystic;the former were more common. There were no characteristic findings which permitted definitive differentiation from other ovarian tumors.

Study of wilms' tumor

International Nuclear Information System (INIS)

Khan, M.H.; Yaqub, N.

2001-01-01

This study is an effort to bring into light data related to children with Wilms' tumor managed at Islamabad as local literature on this topic is lacking. It was retrospective study. The study was conducted at Children Hospital, Pakistan Institute of Medical Science, Islamabad between January, 1987 and December 1995. All patients managed during the study period were included in the study. In all the patients complete blood count (CBC), urine analysis (D/R),X-ray abdomen and chest, ultrasound abdomen and in selected cases CT scan were performed. National Wilms' Tumor Study Group (NWTS 3) protocol was followed for further management. Fifty patients including 28 males and 22 females with the age range from 9 months to 8 years were managed in 9 years period. Left kidney was involved in 31 patients. Most of the tumors were solid on ultrasound, 76% patients were in stage III and IV. In one case bilateral involvement of kidney was found. Forty patients underwent primary surgery. Only 14 patients received complete course of chemotherapy while 31 radiotherapy. Nineteen patients died and 15 lost to follow-up. The survival and mortality rates are comparable to NWTS-3 results, although, most of the patients were presented in advance stage of Wilms tumor. The survival of these patients can be improved by increasing awareness of society through electronic and print media. (author)

Action of the antitumor and antispermatogenic agent lonidamine on electron transport in Ehrlich ascites tumor mitochondria.

Science.gov (United States)

Floridi, A; Lehninger, A L

1983-10-01

The effect of lonidamine, an antispermatogenic and antitumor drug, on the oxygen consumption, ATPase activity, and redox state of the electron carriers of Ehrlich ascites tumor mitochondria has been studied. Lonidamine inhibits ADP- and uncoupler-stimulated respiration on various NAD- and FAD-linked substrates, but does not affect state 4 respiration. Experiments to determine its site of action showed that lonidamine does not significantly inhibit electron flow through cytochrome oxidase. Electron flow through site 2, the ubiquinone-cytochrome b-cytochrome c1 complex, also was unaffected by lonidamine, which failed to inhibit the oxidation of duroquinol. Moreover, inhibition of electron flow through site 2 was also excluded because of the inability of the N,N,N',N'-tetramethyl-p-phenylenediamine bypass to relieve the lonidamine inhibition of the oxidation of pyruvate + malate. The F0F1ATPase activity and vectorial H+ ejection are also unaffected by lonidamine. The inhibition of succinate oxidation by lonidamine was found to take place at a point between succinate and iron-sulfur center S3. Spectroscopic experiments demonstrated that lonidamine inhibits the reduction of mitochondrial NAD+ by pyruvate + malate and other NAD-linked substrates in the transition from state 1 to state 4. However, lonidamine does not inhibit reduction of added NAD+ by submitochondrial vesicles or by soluble purified NAD-linked dehydrogenases. These observations, together with other evidence, suggest that electron transport in tumor mitochondria is inhibited by lonidamine at the dehydrogenase-coenzyme level, particularly when the electron carriers are in a relatively oxidized state and/or when the inner membrane-matrix compartment is in the condensed state. The action of lonidamine in several respects resembles the selective inhibition of electron transport in tumor cells produced by cytotoxic macrophages (D. L. Granger and A. L. Lehninger (1982) J. Cell Biol. 95, 527).

Clinicopathologic features and surgical outcome of solid pseudopapillary tumor of the pancreas: analysis of 17 cases

Directory of Open Access Journals (Sweden)

Wang Xiao-Guang

2013-02-01

Full Text Available Abstract Background We summarize our experience of the diagnosis, surgical treatment, and prognosis of solid pseudopapillary tumors (SPTs. Methods We carried out a retrospective study of clinical data from a series of 17 patients with SPT managed in two hospitals between October 2001 and November 2011. Results All of the 17 patients were female and the average age at diagnosis was 26.6 years (range 11 years to 55 years. The tumor was located in the body or tail in ten patients, the head in five patients, and the neck in two patients. The median tumor size was 5.5 cm (range 2 cm to 10 cm. All 17 patients had curative resections, including seven distal pancreatectomies, five local resections, four pancreaticoduodenectomies, and one central pancreatectomy. Two patients required concomitant splenic vein resection due to local tumor invasion. All patients were alive and disease-free at a median follow-up of 48.2 months (range 2 to 90 months. There were no significant associations between clinicopathologic factors and malignant potential of SPT. Ki-67 was detected in three patients with pancreatic parenchyma invasion. Conclusions The SPT is an infrequent tumor, typically affecting young women without notable symptoms. Surgical resection is justified even in the presence of local invasion or metastases, as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential of SPTs.

Polyphenon-E encapsulated into chitosan nanoparticles inhibited proliferation and growth of Ehrlich solid tumor in mice

Directory of Open Access Journals (Sweden)

Azza I. Othman

2018-03-01

Full Text Available Limited bioavailability of green tea polyphenols hampered their delivery to tumor and hence therapeutic effectiveness. This study investigated the antitumor activity of polyphenon-E (PE encapsulated into chitosan nanoparticles (CSNPs in Ehrlich solid tumor in mice. CSNPs-PE, with a particle size of 53–69 nm showed 83% entrapment efficiency and a sustained release of PE in pH = 7.4 at 37 °C. The data demonstrated a higher percentage of released drug in case of less crosslinked formulations. Ehrlich ascites carcinoma (EAC cells (2.5 × 106/0.2 ml/mouse were injected subcutaneously in the back of mice. Oral administration of CSNPs-PE for 30 days produced a significant decrease in tumor volume (53% and weight (60% compared with free PE and voids CSNPs (72%. Compared with free PE and control, cell cycle revealed G0/G1 arrest associated with decrease in proliferating cell nuclear antigen (PCNA. In tumor tissue of CSNPs-PE treated mice, compared with free PE, there were; 1 induction of Bax and p53, 2 activation of caspases-3,-8 and -9, and CD95, 3 decrease in Bcl-2 expression of 4 inhibition of VEGF and CD31 expressions in tumor tissue. In conclusion, encapsulation of PE into CSNPs provided a good platform for cancer chemotherapy and raised existing application of different polyphenols for nanochemotherapy/prevention.

Quantitative vs. qualitative approaches to the electronic structure of solids

International Nuclear Information System (INIS)

Oliva, J.M.; Llunell, Miquel; Alemany, Pere; Canadell, Enric

2003-01-01

The usefulness of qualitative and quantitative theoretical approaches in solid state chemistry is discussed by considering three different types of problems: (a) the distribution of boron and carbon atoms in MB 2 C 2 (M=Ca, La, etc.) phases, (b) the band structure and Fermi surface of low-dimensional transition metal oxides and bronzes, and (c) the correlation between the crystal and electronic structure of the ternary nitride Ca 2 AuN

Experimental measurements of deep directional columnar heating by laser-generated relativistic electrons at near-solid density

International Nuclear Information System (INIS)

Koch, J.A.; Key, M.H.; Hatchett, S.P.; Lee, R.W.; Pennington, D.; Tabak, M.; Freeman, R.R.; Stephens, R.B.

2002-01-01

In our experiments, we irradiated solid CH targets with a 400 J, 5 ps, 3x10 19 W/cm 2 laser, and we used x-ray imaging and spectroscopic diagnostics to monitor the keV x-ray emission from thin Al or Au tracer layers buried within the targets. The experiments were designed to quantify the spatial distribution of the thermal electron temperature and density as a function of buried layer depth; these data provide insights into the behavior of relativistic electron currents which flow within the solid target and are directly and indirectly responsible for the heating. We measured ∼200-350 eV temperatures and near-solid densities at depths ranging from 5 to 100 μm beneath the target surface. Time-resolved x-ray spectra from Al tracers indicate that the tracers emit thermal x rays and cool slowly compared to the time scale of the laser pulse. Most intriguingly, we consistently observe annular x-ray images in all buried tracer-layer experiments, and these data show that the temperature distribution is columnar, with enhanced heating along the edges of the column. The ring diameters are much greater than the laser focal spot diameter and do not vary significantly with the depth of the tracer layer for depths greater than 30 μm. The local temperatures are 200-350 eV for all tracer depths. We discuss recent simulations of the evolution of electron currents deep within solid targets irradiated by ultra-high-intensity lasers, and we discuss how modeling and analytical results suggest that the annular patterns we observe may be related to locally strong growth of the Weibel instability. We also suggest avenues for future research in order to further illuminate the complex physics of relativistic electron transport and energy deposition inside ultra-high-intensity laser-irradiated solid targets

Therapeutic efficacy and microSPECT/CT imaging of {sup 188}Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

Energy Technology Data Exchange (ETDEWEB)

Chang, Y.-J.; Chang, C.-H.; Yu, C.-Y.; Chang, T.-J.; Chen, L.-C. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, M.-H. [National Health Research Institutes, Miaoli, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Ting Gann [National Health Research Institutes, Miaoli, Taiwan (China)], E-mail: gann.ting@msa.hinet.net

2010-01-15

Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of {sup 188}Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ({sup 188}Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of {sup 188}Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of {sup 188}Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of {sup 188}Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of {sup 188}Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of {sup 188}Re-liposome and the synergistic effect of the combination radiochemotherapeutics of {sup 188}Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of

CT morphology of benign median nerve tumors

International Nuclear Information System (INIS)

Feyerabend, T.; Schmitt, R.; Lanz, U.; Warmuth-Metz, M.; Wuerzburg Univ.

1990-01-01

Computed tomography (CT) was performed in 3 patients with benign tumors of the median nerve, histologically confirmed as neurilemmoma, fibrolipoma and hemangioma. The neurilemmoma showed a ring-shaped contrast enhancement. The fibrolipoma presented with areas of solid soft tissue and areas of fat. The hemangioma was a solid tumor with a lacunar, vascular contrast enhancement. According to our experience and to the previous literature CT gives useful information regarding the anatomic location, size, and relationship of peripheral nerve sheath tumors to surrounding structures, and may help to differentiate between various tumor types. (orig.)

Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice.

Science.gov (United States)

Shiromizu, Shoya; Kusunose, Naoki; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro

2018-04-01

Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Solid-phase characterization in flammable-gas-tank sludges by electron microscopy

International Nuclear Information System (INIS)

Liu, J.; Pederson, L.R.; Qang, L.Q.

1995-09-01

The crystallinity, morphology, chemical composition, and crystalline phases of several Tank 241-SY-101 (hereinafter referred to as SY-101) and Tank 241-SY-103 (hereinafter referred to as SY-103) solid samples were studied by transmission electron microscopy (TEM), electron energy dispersive spectroscopy (EDS), and electron diffraction. The main focus is on the identification of aluminum hydroxide thought to be present in these tank samples. Aluminum hydroxide was found in SY-103, but not in SY-101. This difference can be explained by the different OH/Al ratios found in the two tank samples: a high OH/Al ratio in SY-101 favors the formation of sodium aluminate, but a low OH/Al ratio in SY-103 favors aluminum hydroxide. These results were confirmed by a magnetic resonance study on SY-101 and SY-103 simulant. The transition from aluminum hydroxide to sodium aluminate occurs at an OH/Al molar ratio of 3.6. It is believed that the study of Al(OH) 3 was not affected by sample preparation because all Al(OH) 3 is in the solid form according to the NMR experiments. There is no Al(OH) 3 in the liquid. It is, therefore, most likely that the observation of Al(OH) 3 is representative of the real sludge sample, and is not affected by drying. Similar conclusions also apply to other insoluble phases such as iron and chromium

Not All Next Generation Sequencing Diagnostics are Created Equal: Understanding the Nuances of Solid Tumor Assay Design for Somatic Mutation Detection

Energy Technology Data Exchange (ETDEWEB)

Gray, Phillip N., E-mail: pgray@ambrygen.com; Dunlop, Charles L.M.; Elliott, Aaron M. [Ambry Genetics, 15 Argonaut, Aliso Viejo, CA 92656 (United States)

2015-07-17

The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants.

Fractal structure formation on the surfaces of solids subjected to high intensity electron and ion treatment

International Nuclear Information System (INIS)

Altajskij, M.V.; Ivanov, V.V.; Korenev, S.A.; Orelovich, O.L.; Puzynin, I.V.; Chernik, V.V.

1997-01-01

We discuss the results of scanning electron microscopy of surfaces of the solids subjected to high intensity electron and ion beam treatment. The appearance of fractal structures on the modified surfaces is shown. The fractal dimensions of these structures were estimated by box-counting algorithm

A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors.

Science.gov (United States)

Lin, Jianqing; Gilbert, Jill; Rudek, Michelle A; Zwiebel, James A; Gore, Steve; Jiemjit, Anchalee; Zhao, Ming; Baker, Sharyn D; Ambinder, Richard F; Herman, James G; Donehower, Ross C; Carducci, Michael A

2009-10-01

This was a phase I trial to determine the minimal effective dose and optimal dose schedule for 5-azacytidine (5-AC) in combination with sodium phenylbutyrate in patients with refractory solid tumors. The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. Three dosing regimens were studied in 27 patients with advanced solid tumors, and toxicity was recorded. The pharmacokinetics of the combination of drugs was evaluated. Repeat tumor biopsies and peripheral blood mononuclear cells (PBMC) were analyzed to evaluate epigenetic changes in response to therapy. EBV titers were evaluated as a surrogate measure for gene re-expression of epigenetic modulation in PBMC. The three dose regimens of 5-AC and phenylbutyrate were generally well tolerated and safe. A total of 48 cycles was administrated to 27 patients. The most common toxicities were bone marrow suppression-related neutropenia and anemia, which were minor. The clinical response rate was disappointing for the combination of agents. One patient showed stable disease for 5 months whereas 26 patients showed progressive disease as the best tumor response. The administration of phenylbutyrate and 5-AC did not seem to alter the pharmacokinetics of either drug. Although there were individual cases of targeted DNA methyltransferase activity and histone H3/4 acetylation changes from paired biopsy or PBMC, no conclusive statement can be made based on these limited correlative studies. The combination of 5-AC and phenylbutyrate across three dose schedules was generally well tolerated and safe, yet lacked any real evidence for clinical benefit.

Diagnosis and treatment of solid pseudopapillary tumor of the pancreas: experience of one single institution from Turkey

Science.gov (United States)

2013-01-01

Background Solid pseudopapillary neoplasia (SPN) of the pancreas is an extremely rare epithelial tumor of low malignant potential. SPN accounts for less than 1% to 2% of exocrine pancreatic tumors. The aim of this study is to report our experience with SPN of the pancreas. It includes a summary of the current literature to provide a reference for the management of this rare clinical entity. Methods A retrospective analysis was performed of all patients diagnosed and treated for SPN in our hospital over the past 15 years (1998 to 2013). A database of the characteristics of these patients was developed, including age, gender, tumor location and size, treatment, and histopathological and immunohistochemical features. Results During this time period, 255 patients with pancreatic malignancy (which does not include ampulla vateri, distal choledocal and duodenal tumor) were admitted to our department, only 10 of whom were diagnosed as having SPN (2.5%). Nine patients were women (90%) and one patient was a man (10%). Their median age was 38.8 years (range 18 to 71). The most common symptoms were abdominal pain and dullness. Seven patients (70%) presented with abdominal pain or abdominal dullness and three patient (30%) were asymptomatic with the diagnosis made by an incidental finding on routine examination. Abdominal computed tomography and/or magnetic resonance imaging showed the typical features of solid pseudopapillary neoplasm in six (60%) of the patients. Four patients underwent distal pancreatectomy with splenectomy, one patient underwent a total mass excision, and one patient underwent total pancreatic resection. Two required extended distal pancreatectomy with splenectomy. Two underwent spleen-preserving distal pancreatectomy. Conclusions SPN is a rare neoplasm that primarily affects young women. The prognosis is favorable even in the presence of distant metastasis. Although surgical resection is generally curative, a close follow-up is advised in order to

Electron Paramagnetic Resonance pO2 Image Tumor Oxygen-Guided Radiation Therapy Optimization.

Science.gov (United States)

Epel, Boris; Maggio, Matt; Pelizzari, Charles; Halpern, Howard J

2017-01-01

Modern standards for radiation treatment do not take into account tumor oxygenation for radiation treatment planning. Strong correlation between tumor oxygenation and radiation treatment success suggests that oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. We have developed an OGRT protocol for rodents. Electron paramagnetic resonance (EPR) imaging is used for recording oxygen maps with high spatial resolution and excellent accuracy better than 1 torr. Radiation is delivered with an animal intensity modulated radiation therapy (IMRT) XRAD225Cx micro-CT/ therapy system. The radiation plan is delivered in two steps. First, a uniform 15% tumor control dose (TCD 15 ) is delivered to the whole tumor. In the second step, an additional booster dose amounting to the difference between TCD 98 and TCD 15 is delivered to radio-resistant, hypoxic tumor regions. Delivery of the booster dose is performed using a multiport conformal beam protocol. For radiation beam shaping we used individual radiation blocks 3D-printed from tungsten infused ABS polymer. Calculation of beam geometry and the production of blocks is performed next to the EPR imager, immediately after oxygen imaging. Preliminary results demonstrate the sub-millimeter precision of the radiation delivery and high dose accuracy. The efficacy of the radiation treatment is currently being tested on syngeneic FSa fibrosarcoma tumors grown in the legs of C3H mice.

Pancreatic tumors in children and young adults with tuberous sclerosis complex

International Nuclear Information System (INIS)

Koc, Gonca; Sugimoto, Sam; Kammen, Bamidele F.; Karakas, S.P.; Kuperman, Rachel

2017-01-01

Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex. (orig.)

Pancreatic tumors in children and young adults with tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Koc, Gonca [Erciyes University, School of Medicine, Department of Pediatric Radiology, Melikgazi, Kayseri (Turkey); Sugimoto, Sam; Kammen, Bamidele F.; Karakas, S.P. [UCSF Benioff Children' s Hospital, Department of Diagnostic Imaging, Oakland, CA (United States); Kuperman, Rachel [UCSF Benioff Children' s Hospital, Department of Pediatric Neurology, Oakland, CA (United States)

2017-01-15

Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex. (orig.)

Dynamics of solid inner-shell electrons in collisions with bare and dressed swift ions

International Nuclear Information System (INIS)

Montanari, C.C.; Miraglia, J. E.; Arista, N.R.

2002-01-01

We analyze the dynamical interactions of swift heavy projectiles and solid inner-shell electrons. The dielectric formalism employed to deal with the free-electron gas is extended to account for the core electrons, by using the local plasma approximation. Results for stopping power, energy straggling, and inner-shell ionization in collisions of bare ions with metals are displayed, showing very good accord with the experimental data. Simultaneous excitations of projectile and target electrons are also analyzed. In the high-energy range we find a similar contribution of target core and valence electrons to the probability of projectile-electron loss. The problem of no excitation threshold within the local plasma approximation and the possibility of collective excitations of the shells are discussed

Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

International Nuclear Information System (INIS)

Valous, Nektarios A.; Lahrmann, Bernd; Halama, Niels; Grabe, Niels; Bergmann, Frank; Jäger, Dirk

2016-01-01

not only on percentage content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. Conclusions: The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors.

Science.gov (United States)

Valous, Nektarios A; Lahrmann, Bernd; Halama, Niels; Bergmann, Frank; Jäger, Dirk; Grabe, Niels

2016-06-01

content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

Energy Technology Data Exchange (ETDEWEB)

Valous, Nektarios A. [Applied Tumor Immunity Clinical Cooperation Unit, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg 69120 (Germany); Lahrmann, Bernd; Halama, Niels; Grabe, Niels [Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg 69120 (Germany); Bergmann, Frank [Institute of Pathology, Heidelberg University Hospital, Heidelberg 69120 (Germany); Jäger, Dirk [Department of Medical Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg 69120, Germany and National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg 69120 (Germany)

2016-06-15

not only on percentage content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. Conclusions: The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

Electronically shielded solid state charged particle detector

International Nuclear Information System (INIS)

Balmer, D.K.; Haverty, T.W.; Nordin, C.W.; Tyree, W.H.

1996-01-01

An electronically shielded solid state charged particle detector system having enhanced radio frequency interference immunity includes a detector housing with a detector entrance opening for receiving the charged particles. A charged particle detector having an active surface is disposed within the housing. The active surface faces toward the detector entrance opening for providing electrical signals representative of the received charged particles when the received charged particles are applied to the active surface. A conductive layer is disposed upon the active surface. In a preferred embodiment, a nonconductive layer is disposed between the conductive layer and the active surface. The conductive layer is electrically coupled to the detector housing to provide a substantially continuous conductive electrical shield surrounding the active surface. The inner surface of the detector housing is supplemented with a radio frequency absorbing material such as ferrite. 1 fig

Some implications of Scale Relativity theory in avascular stages of growth of solid tumors in the presence of an immune system response.

Science.gov (United States)

Buzea, C Gh; Agop, M; Moraru, Evelina; Stana, Bogdan A; Gîrţu, Manuela; Iancu, D

2011-08-07

We present a traveling-wave analysis of a reduced mathematical model describing the growth of a solid tumor in the presence of an immune system response in the framework of Scale Relativity theory. Attention is focused upon the attack of tumor cells by tumor-infiltrating cytotoxic lymphocytes (TICLs), in a small multicellular tumor, without necrosis and at some stage prior to (tumor-induced) angiogenesis. For a particular choice of parameters, the underlying system of partial differential equations is able to simulate the well-documented phenomenon of cancer dormancy and propagation of a perturbation in the tumor cell concentration by cnoidal modes, by depicting spatially heterogeneous tumor cell distributions that are characterized by a relatively small total number of tumor cells. This behavior is consistent with several immunomorphological investigations. Moreover, the alteration of certain parameters of the model is enough to induce soliton like modes and soliton packets into the system, which in turn result in tumor invasion in the form of a standard traveling wave. In the same framework of Scale Relativity theory, a very important feature of malignant tumors also results, that even in avascular stages they might propagate and invade healthy tissues, by means of a diffusion on a Newtonian fluid. Copyright © 2011 Elsevier Ltd. All rights reserved.

From the Kohn-Sham band gap to the fundamental gap in solids. An integer electron approach.

Science.gov (United States)

Baerends, E J

2017-06-21

It is often stated that the Kohn-Sham occupied-unoccupied gap in both molecules and solids is "wrong". We argue that this is not a correct statement. The KS theory does not allow to interpret the exact KS HOMO-LUMO gap as the fundamental gap (difference (I - A) of electron affinity (A) and ionization energy (I), twice the chemical hardness), from which it indeed differs, strongly in molecules and moderately in solids. The exact Kohn-Sham HOMO-LUMO gap in molecules is much below the fundamental gap and very close to the much smaller optical gap (first excitation energy), and LDA/GGA yield very similar gaps. In solids the situation is different: the excitation energy to delocalized excited states and the fundamental gap (I - A) are very similar, not so disparate as in molecules. Again the Kohn-Sham and LDA/GGA band gaps do not represent (I - A) but are significantly smaller. However, the special properties of an extended system like a solid make it very easy to calculate the fundamental gap from the ground state (neutral system) band structure calculations entirely within a density functional framework. The correction Δ from the KS gap to the fundamental gap originates from the response part v resp of the exchange-correlation potential and can be calculated very simply using an approximation to v resp . This affords a calculation of the fundamental gap at the same level of accuracy as other properties of crystals at little extra cost beyond the ground state bandstructure calculation. The method is based on integer electron systems, fractional electron systems (an ensemble of N- and (N + 1)-electron systems) and the derivative discontinuity are not invoked.

Final Report: Conceptual Design of an Electron Accelerator for Bio-Solid Waste Treatment

Energy Technology Data Exchange (ETDEWEB)

Cooper, Charles [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

2017-09-20

Several studies have identified electron beam (EB) irradiation of municipal wastewater and bio-solids as an effective and promising approach to the environmental remediation of the enormous quantities of human waste created by a growing world-wide population and increased urbanization. However, despite the technical success of experimental and pilot programs over the last several decades, the technique is still not in commercial use anywhere in the world. In addition, the report also identifies the need for “Financial and infrastructure participation from a utility for demonstration project” and “Education and awareness of safety of utilizing electron beam technology” as two additional roadblocks preventing technology adoption of EB treatment for bio-solids. In this concept design, we begin to address these barriers by working with Metropolitan Water Reclamation District of Greater Chicago (MWRD) and by the applying the latest accelerator technologies developed at Fermilab and within the DOE Office of Science laboratory complex.

The thermodynamical foundation of electronic conduction in solids

Science.gov (United States)

Bringuier, E.

2018-03-01

In elementary textbooks, the microscopic justification of Ohm’s local law in a solid medium starts with Drude’s classical model of electron transport and next discusses the quantum-dynamical and statistical amendments. In this paper, emphasis is laid instead upon the thermodynamical background motivated by the Joule-Lenz heating effect accompanying conduction and the fact that the conduction electrons are thermalized at the lattice temperature. Both metals and n-type semiconductors are considered; but conduction under a magnetic field is not. Proficiency in second-year thermodynamics and vector analysis is required from an undergraduate university student in physics so that the content of the paper can be taught to third-year students. The necessary elements of quantum mechanics are posited in this paper without detailed justification. We start with the equilibrium-thermodynamic notion of the chemical potential of the electron gas, the value of which distinguishes metals from semiconductors. Then we turn to the usage of the electrochemical potential in the description of near-equilibrium electron transport. The response of charge carriers to the electrochemical gradient involves the mobility, which is the reciprocal of the coefficient of the effective friction force opposing the carrier drift. Drude’s calculation of mobility is restated with the dynamical requirements of quantum physics. Where the carrier density is inhomogeneous, there appears diffusion, the coefficient of which is thermodynamically related to the mobility. Next, it is remarked that the release of heat was ignored in Drude’s original model. In this paper, the flow of Joule heat is handled thermodynamically within an energy balance where the voltage generator, the conduction electrons and the host lattice are involved in an explicit way. The notion of dissipation is introduced as the rate of entropy creation in a steady state. The body of the paper is restricted to the case of one

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

Science.gov (United States)

Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

2012-04-01

Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition

International Nuclear Information System (INIS)

Peddaboina, Chander; Smythe, W Roy; Cao, Xiaobo; Jupiter, Daniel; Fletcher, Steven; Yap, Jeremy L; Rai, Arun; Tobin, Richard P; Jiang, Weihua; Rascoe, Philip; Rogers, M Karen Newell

2012-01-01

It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination. The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell lines were determined by western blotting. Annexin-V staining and cleaved PARP western blotting were used to assay for apoptosis. The cellular toxicities after various treatments were measured via the XTT assay. In our current analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL are overexpressed and also co-exist in many tumors and that the expression levels of both genes correlate with the clinical staging. The downregulation of Mcl-1 or Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates with that of Mcl-1 in human cancer tissue samples. We additionally found that the USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and promoted apoptosis in different tumor cells. Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors

Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

Energy Technology Data Exchange (ETDEWEB)

Yamoah, Kosj [Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (United States); Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

2015-11-15

Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: In primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.

Relativistic electron beam interaction and $K_{\\alpha}$-generation in solid targets

CERN Document Server

Fill, E; Eder, D; Eidmann, K; Saemann, A

1999-01-01

When fs laser pulses interact with solid surfaces at intensities I lambda /sup 2/ >10/sup 18/ W/cm/sup 2/ mu m/sup 2/, collimated relativistic electron beams are generated. These electrons can be used for producing intense X-radiation (bremsstrahlung or K/sub alpha /) for pumping an innershell X-ray laser. The basic concept of such a laser involves the propagation of the electron beam in a material which converts electron energy into appropriate pump photons. Using the ATLAS titanium-sapphire laser at Max-Planck-Institut fur Quantenoptik, we investigate the generation of hot electrons and of characteristic radiation in copper. The laser (200 mJ/130 fs) is focused by means of an off-axis parabola to a diameter of about 10 mu m. By varying the position of the focus, we measure the copper K/sub alpha /-yield as a function of intensity in a range from 10/sup 15/ to 2 x 10/sup 18/ W/cm/sup 2/ while keeping the laser pulse energy constant. Surprisingly, the highest emission is obtained at an intensity of about 10/s...

A Case of Renal Primitive Neuroectodermal Tumor Confirmed by Fluorescence in situ Hybridization

Directory of Open Access Journals (Sweden)

Toshiki Etani

2015-04-01

Full Text Available Primitive neuroectodermal tumor (PNET is a member of the Ewing's sarcoma family of tumors (ESFT. We report a case of PNET in a 66-year-old male who presented with a large solid tumor within the parenchyma of the middle pole of the left kidney with metastases to the left adrenal gland and right ischium. A fine-needle biopsy was performed and showed a small round cell tumor. Results of immunohistochemical staining suggested this tumor belonged to ESFT. Preoperative VDC-IE (combined vincristine, doxorubicin and cyclophosphamide followed by another combination of ifosfamide and etoposide chemotherapy and left radical nephrectomy and adrenalectomy were performed. The histopathological findings of the resected tumor were similar to those in the biopsy specimen, but the results of AE1/AE3 were different. For the diagnosis, fluorescence in situ hybridization was performed. Split signals of the EWSR1 gene were detected, and transmission electron microscopy showed neuroendocrine granules and microtubules. The final diagnosis of this tumor was PNET of the kidney.

Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

Science.gov (United States)

Maranchie, Jodi K; Afonso, Anoushka; Albert, Paul S; Kalyandrug, Sivaram; Phillips, John L; Zhou, Shubo; Peterson, James; Ghadimi, Bijan M; Hurley, Katheen; Riss, Joseph; Vasselli, James R; Ried, Thomas; Zbar, Berton; Choyke, Peter; Walther, McClellan M; Klausner, Richard D; Linehan, W Marston

2004-01-01

von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. Copyright 2003 Wiley-Liss, Inc.

Correlating Intravital Multi-Photon Microscopy to 3D Electron Microscopy of Invading Tumor Cells Using Anatomical Reference Points

Science.gov (United States)

Karreman, Matthia A.; Mercier, Luc; Schieber, Nicole L.; Shibue, Tsukasa; Schwab, Yannick; Goetz, Jacky G.

2014-01-01

Correlative microscopy combines the advantages of both light and electron microscopy to enable imaging of rare and transient events at high resolution. Performing correlative microscopy in complex and bulky samples such as an entire living organism is a time-consuming and error-prone task. Here, we investigate correlative methods that rely on the use of artificial and endogenous structural features of the sample as reference points for correlating intravital fluorescence microscopy and electron microscopy. To investigate tumor cell behavior in vivo with ultrastructural accuracy, a reliable approach is needed to retrieve single tumor cells imaged deep within the tissue. For this purpose, fluorescently labeled tumor cells were subcutaneously injected into a mouse ear and imaged using two-photon-excitation microscopy. Using near-infrared branding, the position of the imaged area within the sample was labeled at the skin level, allowing for its precise recollection. Following sample preparation for electron microscopy, concerted usage of the artificial branding and anatomical landmarks enables targeting and approaching the cells of interest while serial sectioning through the specimen. We describe here three procedures showing how three-dimensional (3D) mapping of structural features in the tissue can be exploited to accurately correlate between the two imaging modalities, without having to rely on the use of artificially introduced markers of the region of interest. The methods employed here facilitate the link between intravital and nanoscale imaging of invasive tumor cells, enabling correlating function to structure in the study of tumor invasion and metastasis. PMID:25479106

Study on the surface electronic properties of Li-containing solids

Energy Technology Data Exchange (ETDEWEB)

Matsuura, Fumio; Suzuki, Atsushi; Yamaguchi, Kenji; Yamawaki, M [Tokyo Univ. (Japan)

1998-03-01

The electronic state of Li{sub 2}O surface will be modified by absorption and/or desorption of chemically-active species, such as H{sub 2} and H{sub 2}O. The reactions induced by these species will involve some point defects in the solid. Whereas the high temperature Kelvin probe has proven to be quite effective in obtaining information on the surface reactions between gas and solid, an attempt is being made to incorporate numerical calculation to obtain further information which may not be easily done by experiments. The code employed in the present study is `CRYSTAL`, which employs a self-consistent-field Hartree-Fock method. As a preliminary study, we tried to calculate the change of Fermi Energy as a function of the density of oxygen vacancy. The results revealed that the greater the density of oxygen vacancy, the larger the Fermi Energy of Li{sub 2}O, which was consistent with the experimental results obtained by high temperature Kelvin probe. (author)

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

Science.gov (United States)

Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

2014-12-01

Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it

Field distribution and DNA transport in solid tumors during electric field-mediated gene delivery.

Science.gov (United States)

Henshaw, Joshua W; Yuan, Fan

2008-02-01

Gene therapy has a great potential in cancer treatment. However, the efficacy of cancer gene therapy is currently limited by the lack of a safe and efficient means to deliver therapeutic genes into the nucleus of tumor cells. One method under investigation for improving local gene delivery is based on the use of pulsed electric field. Despite repeated demonstration of its effectiveness in vivo, the underlying mechanisms behind electric field-mediated gene delivery remain largely unknown. Without a thorough understanding of these mechanisms, it will be difficult to further advance the gene delivery. In this review, the electric field-mediated gene delivery in solid tumors will be examined by following individual transport processes that must occur in vivo for a successful gene transfer. The topics of examination include: (i) major barriers for gene delivery in the body, (ii) distribution of electric fields at both cell and tissue levels during the application of external fields, and (iii) electric field-induced transport of genes across each of the barriers. Through this approach, the review summarizes what is known about the mechanisms behind electric field-mediated gene delivery and what require further investigations in future studies.

Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

Science.gov (United States)

Ghaghada, Ketan B; Sato, Amy F; Starosolski, Zbigniew A; Berg, John; Vail, David M

2016-01-01

Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Liposomal-I resulted in significant (p contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of

Electron polarizability of crystalline solids in quantizing magnetic fields and topological gap numbers

Czech Academy of Sciences Publication Activity Database

Středa, Pavel; Jonckheere, T.; Martin, T.

2008-01-01

Roč. 100, - (2008), 146804/1-146804/4 ISSN 0031-9007 R&D Projects: GA ČR GA202/05/0365 Institutional research plan: CEZ:AV0Z10100521 Keywords : electron polarizability * quantum Hall effect * topological numbers Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 7.180, year: 2008

Problems in the measurement of electron-dose distribution with film dosimeters inserted into solid materials

International Nuclear Information System (INIS)

Okuda, Shuichi; Fukuda, Kyue; Tabata, Tatsuo; Okabe, Shigeru

1981-01-01

On the insertion of film dosimeters into solid materials, thin air gaps are formed. The influence of such gaps on measured profiles of depth-dose distributions was investigated for aluminum irradiated with collimated beams of 15-MeV electrons. Measurements were made by changing the gap width or the incidence angle of the electrons. The present results showed that streaming of incident electrons through the gaps resulted in the appearance of a peak and a minimum in a depth-dose curve measured. This effect was suppressed by the increase of the angle between the film and the electron-beam axis. (author)

A Monte Carlo based development of a cavity theory for solid state detectors irradiated in electron beams

International Nuclear Information System (INIS)

Mobit, P.

2002-01-01

Recent Monte Carlo simulations have shown that the assumption in the small cavity theory (and the extension of the small cavity theory by Spencer-Attix) that the cavity does not perturb the electron fluence is seriously flawed. For depths beyond d max not only is there a significant difference between the energy spectra in the medium and in the solid cavity materials but there is also a significant difference in the number of low-energy electrons which cannot travel across the solid cavity and hence deposit their dose in it (i.e. stopper electrons whose residual range is less than the cavity thickness). The number of these low-energy electrons that are not able to travel across the solid state cavity increases with depth and effective thickness of the detector. This also invalidates the assumption in the small cavity theory that most of the dose deposited in a small cavity is delivered by crossers. Based on Monte Carlo simulations, a new cavity theory for solid state detectors irradiated in electron beams has been proposed as: D med (p)=D det (p) x s S-A med.det x gamma(p) e x S T , where D med (p) is the dose to the medium at point, p, D det (p) is the average detector dose to the same point, s S-A med.det is the Spencer-Attix mass collision stopping power ratio of the medium to the detector material, gamma(p) e is the electron fluence perturbation correction factor and S T is a stopper-to-crosser correction factor to correct for the dependence of the stopper-to-crosser ratio on depth and the effective cavity size. Monte Carlo simulations have been computed for all the terms in this equation. The new cavity theory has been tested against the Spencer-Attix cavity equation as the small cavity limiting case and also Monte Carlo simulations. The agreement between this new cavity theory and Monte Carlo simulations is within 0.3%. (author)

Searches for the electron electric dipole moment and nuclear anapole moments in solids

International Nuclear Information System (INIS)

Mukhamedjanov, T.N.; Sushkov, O.P.; Cadogan, J.M.; Dzuba, V.A.

2004-01-01

Full text: We consider effects caused by the electron electric dipole moment (EDM) in gadolinium garnets. Our estimates show that the experimental studies of these effects could improve the current upper limit on the electron EDM by several orders of magnitude. We suggest a consistent theoretical model and perform calculations of observable effects in gadolinium gallium garnet and gadolinium iron garnet. It is also possible to probe for nuclear anapole moments in a solid state experiment. We suggest such NMR-type experiment and perform estimates of the expected results

Solid state lasers: a major direction in quantum electronics

International Nuclear Information System (INIS)

Shcherbakov, I.A.

2004-01-01

The aim of the report is to analyze development of solid-state lasers (SSL) as one of the most important avenues of the quantum electronics. The obtained intensity of a laser radiation at the focus equal to 5x10 1 0 W/cm 2 (the field intensity equal to about 5x10 1 0 V/cm 2 ) is noted to enable to observe nonlinear quantum- electrodynamic effects. Besides, one managed to increase the SSL efficiency conventionally equal to maximum 3% up to 48-50%. Paper describes new types of SSLs, namely, the crystalline fiber lasers with the lateral gradient of the index of refraction [ru

Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies.

Science.gov (United States)

Wu, Jiayuan; Hu, Liren; Chen, Manyu; Cao, Wenjun; Chen, Haicong; He, Taiping

2016-01-01

The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed- or random-effects models, depending on the heterogeneity of the included studies. We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44-2.11; Pdigestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers.

A Practical and Portable Solids-State Electronic Terahertz Imaging System

Directory of Open Access Journals (Sweden)

Ken Smart

2016-04-01

Full Text Available A practical compact solid-state terahertz imaging system is presented. Various beam guiding architectures were explored and hardware performance assessed to improve its compactness, robustness, multi-functionality and simplicity of operation. The system performance in terms of image resolution, signal-to-noise ratio, the electronic signal modulation versus optical chopper, is evaluated and discussed. The system can be conveniently switched between transmission and reflection mode according to the application. A range of imaging application scenarios was explored and images of high visual quality were obtained in both transmission and reflection mode.

Two-photon excited fluorescence imaging of the pancreatic solid pseudopapillary tumor without hematoxylin and eosin stains.

Science.gov (United States)

Xu, Yahao; Liao, Chenxi; Chen, Jing; Chen, Youting; Zhu, Xiaoqin; Chen, Jianxin

2016-05-01

Solid pseudopapillary tumor (SPT) of the pancreas is an epithelial tumor with low-grade malignant potential and present more common in females. At present, the gold standard for accurate diagnosis of pancreatic tumor was mostly depending on the pathological and/or cytological evaluation. In this work, TPEF microscopy was applied to obtain the images of human normal pancreas and SPT of the pancreas without hematoxylin and eosin (H&E) staining, for the purpose of identifying the organization structural, cell morphological, and cytoplasm changing, which were then compared to their corresponding H&E stained histopathological results. Our results showed that high-resolution TPEF imaging of the pancreatic SPT can clearly distinguish the pathological features from normal pancreas in unstained histological sections, and the results are consistent with the histological results. Moreover, we measured the nuclear-cytoplasmic ratios of the pancreatic SPT and normal pancreas to characterize their difference in the cytomorphological feature. It indicated that this technique can achieve the consistent information of pathological diagnosis, and has the potential to substantially improve the optical diagnosis and treatment of the pancreatic SPT without H&E staining in the future. SCANNING 38:245-250, 2016. © 2015 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors.

Science.gov (United States)

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Kumagai, Michiaki; Nomoto, Takahiro; Aoki, Ichio; Terada, Yasuko; Kishimura, Akihiro; Nishiyama, Nobuhiro; Kataoka, Kazunori

2014-01-28

Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Photoelectron transport in the surface region of solids: universal analytical formalism for quantitative applications of electron spectroscopies

International Nuclear Information System (INIS)

Jablonski, A

2015-01-01

An advanced analytical theory describing electron transport in the surface region of solids may have accuracy comparable to Monte Carlo simulations of electron trajectories, however such an approach requires knowledge of a parameter called the single scattering albedo. This parameter is material dependent and can be calculated from the elastic mean free path and transport mean free path for signal electrons. An attempt is made to derive a simple expression that accurately describes the energy dependence of single scattering albedo in a wide energy range from 50 eV to 30 keV for 78 elemental solids. For these solids and the considered energy range, the mean percentage deviations between the reference values and values calculated from the fitted function were found to be generally well below 1%; the largest value of this deviation was equal to 0.86% (europium). Calculation of the single scattering albedo with high accuracy requires only five fitted coefficients for a given element. Recommendations are also given for calculations of this parameter for compounds. Different predictive formulas expressed in terms of the single scattering albedo are briefly discussed. (paper)

Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study

DEFF Research Database (Denmark)

Bak, Martin; Teglbjaerg, P S

1989-01-01

reaction for neuron-specific enolase (NSE) was found in three tumors and a positive reaction for chromogranin was found in one tumor. On electron microscopic study, intracytoplasmic whorls of intermediate filaments were seen in the perinuclear area. Dense core "neurosecretory" granules were rarely seen......Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation...

First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors

DEFF Research Database (Denmark)

Abdul Razak, Albiruni R; Mau-Sørensen, Morten; Gabrail, Nashat Y

2016-01-01

PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. PATIENTS AND METHODS: In total, 189 patients with advanced solid tumors...

Prognostic impact of the integration of volumetric quantification of the solid part of the tumor on 3DCT and FDG-PET imaging in clinical stage IA adenocarcinoma of the lung.

Science.gov (United States)

Furumoto, Hideyuki; Shimada, Yoshihisa; Imai, Kentaro; Maehara, Sachio; Maeda, Junichi; Hagiwara, Masaru; Okano, Tetsuya; Masuno, Ryuhei; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2018-07-01

The aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis). We enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUV max ) of F 18 -fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes. Univariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p  2.4 and solid-part volume > 779 mm 3 versus those with SUV max  ≤ 2.4 or solid-part volume ≤779 mm 3 were 81.2% versus 98.3% (p IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUV max was highly beneficial for the prediction of survival and pathological invasiveness. Copyright © 2018 Elsevier B.V. All rights reserved.

Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors12

Science.gov (United States)

Hovelson, Daniel H.; McDaniel, Andrew S.; Cani, Andi K.; Johnson, Bryan; Rhodes, Kate; Williams, Paul D.; Bandla, Santhoshi; Bien, Geoffrey; Choppa, Paul; Hyland, Fiona; Gottimukkala, Rajesh; Liu, Guoying; Manivannan, Manimozhi; Schageman, Jeoffrey; Ballesteros-Villagrana, Efren; Grasso, Catherine S.; Quist, Michael J.; Yadati, Venkata; Amin, Anmol; Siddiqui, Javed; Betz, Bryan L.; Knudsen, Karen E.; Cooney, Kathleen A.; Feng, Felix Y.; Roh, Michael H.; Nelson, Peter S.; Liu, Chia-Jen; Beer, David G.; Wyngaard, Peter; Chinnaiyan, Arul M.; Sadis, Seth; Rhodes, Daniel R.; Tomlins, Scott A.

2015-01-01

Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with 95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts. PMID:25925381

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

Science.gov (United States)

2018-05-15

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

High-order harmonic generation in solid slabs beyond the single-active-electron approximation

Science.gov (United States)

Hansen, Kenneth K.; Deffge, Tobias; Bauer, Dieter

2017-11-01

High-harmonic generation by a laser-driven solid slab is simulated using time-dependent density functional theory. Multiple harmonic plateaus up to very high harmonic orders are observed already at surprisingly low field strengths. The full all-electron harmonic spectra are, in general, very different from those of any individual Kohn-Sham orbital. Freezing the Kohn-Sham potential instead is found to be a good approximation for the laser intensities and harmonic orders considered. The origins of the plateau cutoffs are explained in terms of band gaps that can be reached by Kohn-Sham electrons and holes moving through the band structure.

Imaging of pancreatic tumors

International Nuclear Information System (INIS)

Brambs, Hans-Juergen; Juchems, Markus

2010-01-01

Ductal adenocarcinoma is the most frequent solid tumor of the pancreas. This tumor has distinct features including early obstruction of the pancreatic duct, diminished enhancement after administration of contrast material due to desmoplastic growth, high propensity to infiltrate adjacent structures and to metastasize into the liver and the peritoneum. Hormone active endocrine tumors cause specific clinical symptoms. Imaging is aimed at localization of these hypervascular tumors. Non hormone active tumors are most frequently malignant and demonstrate very varying features. Cystic pancreatic tumors are increasingly detected by means of cross sectional imaging. Exact classification can be achieved with knowledge of the macropathology and considering clinical presentation as well as age and gender of the patients. (orig.)

Obstacles and opportunities in the commercialization of the solid-state-electronic fluorescent-lighting ballast

Energy Technology Data Exchange (ETDEWEB)

Johnson, D.R.; Marcus, A.A.; Campbell, R.S.; Sommers, P.; Skumatz, L.; Berk, B.; Petty, P.; Eschbach, C.

1981-10-01

The Solid State Ballast (SSB) Program, aimed at improving the efficiency of fluorescent lights, is described. The first generation of solid state electronic ballasts has been developed and the technology has been transferred to the private sector. This report examines the opportunities for rapid dissemination of this technology into the marketplace. It includes a description of product characteristics and their influence on the commercialization of the SSB, a description of the technology delivery system presently used by the ballast industry, an analysis of the market for SSB, and identification of some high-leverage opportunities to accelerate the commercialization process. (MCW)

Transcriptional response to hypoxia in human tumors.

NARCIS (Netherlands)

Lal, A.; Peters, H.; Croix, B. St.; Haroon, Z.A.; Dewhirst, M.W.; Strausberg, R.L.; Kaanders, J.H.A.M.; Kogel, A.J. van der; Riggins, G.J.

2001-01-01

BACKGROUND: The presence of hypoxic regions within solid tumors is associated with a more malignant tumor phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumors alter gene expression, resulting in resistance to therapy.

Novel anti-c-Mpl monoclonal antibodies identified multiple differentially glycosylated human c-Mpl proteins in megakaryocytic cells but not in human solid tumors.

Science.gov (United States)

Zhan, Jinghui; Felder, Barbara; Ellison, Aaron R; Winters, Aaron; Salimi-Moosavi, Hossein; Scully, Sheila; Turk, James R; Wei, Ping

2013-06-01

Thrombopoietin and its cognate receptor, c-Mpl, are the primary molecular regulators of megakaryocytopoiesis and platelet production. To date the pattern of c-Mpl expression in human solid tumors and the distribution and biochemical properties of c-Mpl proteins in hematopoietic tissues are largely unknown. We have recently developed highly specific mouse monoclonal antibodies (MAb) against human c-Mpl. In this study we used these antibodies to demonstrate the presence of full-length and truncated human c-Mpl proteins in various megakaryocytic cell types, and their absence in over 100 solid tumor cell lines and in the 12 most common primary human tumor types. Quantitative assays showed a cell context-dependent distribution of full-length and truncated c-Mpl proteins. All forms of human c-Mpl protein were found to be modified with extensive N-linked glycosylation but different degrees of sialylation and O-linked glycosylation. Of note, different variants of full-length c-Mpl protein exhibiting differential glycosylation were expressed in erythromegakaryocytic leukemic cell lines and in platelets from healthy human donors. This work provides a comprehensive analysis of human c-Mpl mRNA and protein expression on normal and malignant hematopoietic and non-hematopoietic cells and demonstrates the multiple applications of several novel anti-c-Mpl antibodies.

Remodeling of Tumor Stroma and Response to Therapy

Energy Technology Data Exchange (ETDEWEB)

Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

2012-03-27

Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

Remodeling of Tumor Stroma and Response to Therapy

International Nuclear Information System (INIS)

Johansson, Anna; Ganss, Ruth

2012-01-01

Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors.

Science.gov (United States)

Herbst, Roy S; Hong, David; Chap, Linnea; Kurzrock, Razelle; Jackson, Edward; Silverman, Jeffrey M; Rasmussen, Erik; Sun, Yu-Nien; Zhong, Don; Hwang, Yuying C; Evelhoch, Jeffrey L; Oliner, Jonathan D; Le, Ngocdiep; Rosen, Lee S

2009-07-20

PURPOSE AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. PATIENTS AND METHODS Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti-AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K(trans); measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. CONCLUSION Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor-axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient

Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

International Nuclear Information System (INIS)

Bonde, Anne-Katrine; Tischler, Verena; Kumar, Sushil; Soltermann, Alex; Schwendener, Reto A

2012-01-01

Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Data presented here identify a novel role for macrophages in EMT

Electron correlations in solid state physics

International Nuclear Information System (INIS)

Freericks, J.K.

1991-04-01

Exactly solvable models of electron correlations in solid state physics are presented. These models include the spinless Falicov- Kimball model, the t-t'-J model, and the Hubbard model. The spinless Falicov-Kimball model is analyzed in one-dimension. Perturbation theory and numerical techniques are employed to determine the phase diagram at zero temperature. A fractal structure is found where the ground-state changes (discontinuously) at each rational electron filling. The t-t'-J model (strongly interacting limit of a Hubbard model) is studied on eight-site small clusters in the simple-cubic, body-centered-cubic, face-centered-cubic, and square lattices. Symmetry is used to simplify the problem and determine the exact many-body wavefunctions. Ground states are found that exhibit magnetic order or heavy-fermionic character. Attempts to extrapolate to the thermodynamic limit are also made. The Hubbard model is examined on an eight-site square-lattice cluster in the presence of and in the absence of a ''magnetic field'' that couples only to orbital motion. A new magnetic phase is discovered for the ordinary Hubbard model at half-filling. In the ''magnetic field'' case, it is found that the strongly frustrated Heisenberg model may be studied from adiabatic continuation of a tight-binding model (from weak to strong coupling) at one point. The full symmetries of the Hamiltonian are utilized to make the exact diagonalization feasibile. Finally, the presence of ''hidden'' extra symmetry for finite size clusters with periodic boundary conditions is analyzed for a variety of clusters. Moderately sized systems allow nonrigid transformations that map a lattice onto itself preserving its neighbor structure; similar operations are not present in smaller or larger systems. The additional symmetry requires particular representations of the space group to stick together explaining many puzzling degeneracies found in exact diagonalization studies

Validation and Application of a Custom-Designed Targeted Next-Generation Sequencing Panel for the Diagnostic Mutational Profiling of Solid Tumors.

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Guy Froyen

Full Text Available The inevitable switch from standard molecular methods to next-generation sequencing for the molecular profiling of tumors is challenging for most diagnostic laboratories. However, fixed validation criteria for diagnostic accreditation are not in place because of the great variability in methods and aims. Here, we describe the validation of a custom panel of hotspots in 24 genes for the detection of somatic mutations in non-small cell lung carcinoma, colorectal carcinoma and malignant melanoma starting from FFPE sections, using 14, 36 and 5 cases, respectively. The targeted hotspots were selected for their present or future clinical relevance in solid tumor types. The target regions were enriched with the TruSeq approach starting from limited amounts of DNA. Cost effective sequencing of 12 pooled libraries was done using a micro flow cell on the MiSeq and subsequent data analysis with MiSeqReporter and VariantStudio. The entire workflow was diagnostically validated showing a robust performance with maximal sensitivity and specificity using as thresholds a variant allele frequency >5% and a minimal amplicon coverage of 300. We implemented this method through the analysis of 150 routine diagnostic samples and identified clinically relevant mutations in 16 genes including KRAS (32%, TP53 (32%, BRAF (12%, APC (11%, EGFR (8% and NRAS (5%. Importantly, the highest success rate was obtained when using also the low quality DNA samples. In conclusion, we provide a workflow for the validation of targeted NGS by a custom-designed pan-solid tumor panel in a molecular diagnostic lab and demonstrate its robustness in a clinical setting.

Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors

DEFF Research Database (Denmark)

Clausen, Malene M.; Hansen, Anders Elias; af Rosenschold, Per Munck

2013-01-01

: Positron emission tomography/computed tomography (PET/CT) scans of five spontaneous canine solid tumors were included. FDG-PET/CT was obtained at day 1, 64Cu-ATSM at day 2 and 3 (3 and 24 h pi.). GTV was delineated and CT images were co-registered. Sub-volumes for 3 h and 24 h 64Cu-ATSM (Cu3 and Cu24) were...

Promotion of Tumor Invasion by Cooperation of Granulocytes and Macrophages Activated by Anti-tumor Antibodies

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Emilio Barbera-Guillem

1999-11-01

Full Text Available We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.

Advantages of a monochromated transmission electron microscope for solid state physics

International Nuclear Information System (INIS)

Grogger, W.; Kothleitner, G.; Hofer, F.

2006-01-01

Full text: The characterization of nanostructured devices and functional materials at a nanometer scale is paramount for the understanding of their physical and chemical properties. Transmission electron microscopy (TEM) plays a central role, especially in terms of structural and chemical analysis on a nearly atomic scale. In particular, electron energy-loss spectrometry (EELS) can obtain information not only about the chemical composition of a thin sample, but also about chemical bonding and electronic structure (ionization edge fine structures) and optical properties (through valence loss EELS). Recent instrumental advances like monochromators for the electron gun in the TEM have made it possible to reduce the energy resolution to 0.15 eV at an acceleration voltage of 200 kV. Another strong point of the method lies in the combination with a fine electron probe (0.2 nm) which allows to record EELS spectra with high energy resolution and spatial resolution in the range of 1 nm. The improved energy resolution opens new possibilities for studying detailed electronic structure and bonding effects in solids such as transmission metal oxides. The experimental results will be compared with x-ray absorption spectroscopy and band structure calculations. A better energy-resolution is particularly important for measurements in the low loss region of the EELS spectrum which provides the information about the band gap and the dielectric function. We will highlight the potential of the method for studying metallic nanoparticles and semiconducting devices. Additionally, the influence of the intrinsic effects like core-hole and excited lifetime broadening and delocalization of the inelastically scattered electrons will be discussed. (author)

All-Solid-State Textile Batteries Made from Nano-Emulsion Conducting Polymer Inks for Wearable Electronics

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Tapani Ryhänen

2012-08-01

Full Text Available A rollable and all-solid-state textile lithium battery based on fabric matrix and polymer electrolyte that allows flexibility and fast-charging capability is reported. When immerged into poly(3,4-ethylenedioxythiophene (PEDOT nano-emulsion inks, an insulating fabric is converted into a conductive battery electrode for a fully solid state lithium battery with the highest specific energy capacity of 68 mAh/g. This is superior to most of the solid-state conducting polymer primary and/or secondary batteries reported. The bending radius of such a textile battery is less than 1.5 mm while lightening up an LED. This new material combination and inherent flexibility is well suited to provide an energy source for future wearable and woven electronics.

Vacuum ultra-violet and electron energy loss spectroscopy of gaseous and solid organic compounds

International Nuclear Information System (INIS)

Koch, E.E.; Otto, A.

1976-01-01

The experimental arrangements used by the authors for the study of optical vacuum ultra-violet and electron energy loss spectra of organic compounds are described and some theoretical aspects of studies of higher excited states are considered. Results for alkanes, benzene, naphthalene, anthracene and some more complex hydrocarbons are reviewed. Recent results obtained by reflection and electron energy loss spectroscopy for single crystals of anthracene are included and their relevance for gas phase work as well as for the understanding of exciton effects in organic solids is described. (author)

Monolayer self-assembly at liquid-solid interfaces: chirality and electronic properties of molecules at surfaces

International Nuclear Information System (INIS)

Amabilino, David B; Gomar-Nadal, Elba; Veciana, Jaume; Rovira, Concepcio; Iavicoli, Patrizia; PuigmartI-Luis, Josep; Feyter, Steven De; Abdel-Mottaleb, Mohamed M; Mamdouh, Wael; Psychogyiopoulou, Krystallia; Xu Hong; Lazzaroni, Roberto; Linares, Mathieu; Minoia, Andrea

2008-01-01

The spontaneous formation of supramolecular assemblies at the boundary between solids and liquids is a process which encompasses a variety of systems with diverse characteristics: chemisorbed systems in which very strong and weakly reversible bonds govern the assembly and physisorbed aggregates which are dynamic thanks to the weaker interactions between adsorbate and surface. Here we review the interest and advances in the study of chiral systems at the liquid-solid interface, and also the application of this configuration for the study of systems of interest in molecular electronics, self-assembled from the bottom up

Electron microscopic observations and DNA chain fragmentation studies on apoptosis in bone tumor cells induced by 153Sm-EDTMP

International Nuclear Information System (INIS)

Zhu Shoupeng; Xiao Dong; Han Xiaofeng

1997-01-01

The morphological changes observed by electron microscopy indicate that after internal irradiation with 153 Sm-EDTMP bone tumor cells displayed feature of apoptosis, such as margination of condensed chromatin, chromatin fragmentation, as well as the membrane bounded apoptotic bodies formation. The quantification analysis of fragmentation DNA for bone tumor cells induced by 153 Sm-EDTMP shows that the DNA fragmentation is enhanced with the prolongation of internally irradiated time. These characteristics suggest that 153 Sm-EDTMP internal irradiation could induce bone tumor cells to go to apoptosis

A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors

Directory of Open Access Journals (Sweden)

Ying G

2013-01-01

Full Text Available Zhongling Zhu,1,4 Zhengzi Qian,2,4 Zhao Yan,1,4 Cuicui Zhao,2,4 Huaqing Wang,2,4 Guoguang Ying3,41Department of Clinical Pharmacology, 2Department of Lymphoma, 3Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; 4Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of ChinaBackground: Ursolic acid is a promising anticancer agent. The current study aims to evaluate the single- and multiple-dose pharmacokinetics (PK as well as the safety of ursolic acid nanoliposomes (UANL in healthy volunteers and in patients with advanced solid tumors.Methods: Twenty-four healthy volunteers in the single-dose PK study were divided into three different groups, which received 37, 74, and 98 mg/m2 of UANL. Eight patients in the multiple-dose PK study were administered with 74 mg/m2 of UANL daily for 14 days. The UA plasma concentrations were determined using ultra-performance liquid chromatograph-tandem mass spectrometry.Results: The plasma concentration profiles of all subjects were characterized by a biexponential decline after infusion. The mean peak plasma concentration (Cmax increased linearly as a function of the dose (r = 0.999. The mean area under the plasma concentration-time curve (AUC from 0 to 16 hours also increased proportionally with dose escalation (r = 0.998. However, the clearance was constant over the specific dose interval. In the multiple-dose PK study, the trough and average concentrations remained low. The mean AUC, half-life, Cmax, time to Cmax, and the volume of distribution on the first day were similar to those on the last day. All subjects tolerated the treatments well. Most UANL-associated adverse events varied from mild to moderate.Conclusions: UANL exhibits relatively linear PK behavior with dose levels from 37 mg/m2 to 98 mg/m2. No drug accumulation was observed with repeated doses of UANL. The intravenous infusion of UANL was well

Tumor stem cells: A new approach for tumor therapy (Review)

Science.gov (United States)

MENG, MIN; ZHAO, XIN-HAN; NING, QIAN; HOU, LEI; XIN, GUO-HONG; LIU, LI-FENG

2012-01-01

Recent studies have demonstrated the existence of a minority of tumor cells possessing the stem cell properties of self-renewal and differentiation in leukemia and several solid tumors. However, these cells do not possess the normal regulatory mechanisms of stem cells. Following transplantation, they are capable of initiating tumorigenesis and are therefore known as ‘tumor stem cells’. Cellular origin analysis of tumor stem cells has resulted in three hypotheses: Embryonal rest hypothesis, anaplasia and maturation arrest. Several signaling pathways which are involved in carcinogenesis, including Wnt/β-catenin, Notch and Oct-4 signaling pathways are crucial in normal stem cell self-renewal decisions, suggesting that breakdown in the regulation of self-renewal may be a key event in the development of tumors. Thus, tumors can be regarded as an abnormal organ in which stem cells have escaped from the normal constraints on self-renewal, thus, leading to abnormally differentiated tumor cells that lose the ability to form tumors. This new model for maligancies has significance for clinical research and treatment. PMID:22844351

Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors

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Yongkun Sun

2016-10-01

Full Text Available Abstract Background Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. Methods Anlotinib (5–16 mg was orally administered in patients with solid tumor once a day on two schedules: (1 four consecutive weeks (4/0 or (2 2-week on/1-week off (2/1. Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed. Results On the 4/0 schedule, dose-limiting toxicity (DLT was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation. Conclusions At the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.

CAR-T cell therapy in gastrointestinal tumors and hepatic carcinoma: From bench to bedside.

Science.gov (United States)

Zhang, Qi; Zhang, Zimu; Peng, Meiyu; Fu, Shuyu; Xue, Zhenyi; Zhang, Rongxin

2016-01-01

The chimeric antigen receptor (CAR) is a genetically engineered receptor that combines a scFv domain, which specifically recognizes the tumor-specific antigen, with T cell activation domains. CAR-T cell therapies have demonstrated tremendous efficacy against hematologic malignancies in many clinical trials. Recent studies have extended these efforts to the treatment of solid tumors. However, the outcomes of CAR-T cell therapy for solid tumors are not as remarkable as the outcomes have been for hematologic malignancies. A series of hurdles has arisen with respect to CAR-T cell-based immunotherapy, which needs to be overcome to target solid tumors. The major challenge for CAR-T cell therapy in solid tumors is the selection of the appropriate specific antigen to demarcate the tumor from normal tissue. In this review, we discuss the application of CAR-T cells to gastrointestinal and hepatic carcinomas in preclinical and clinical research. Furthermore, we analyze the usefulness of several specific markers in the study of gastrointestinal tumors and hepatic carcinoma.

Escaping Electrons from Intense Laser-Solid Interactions as a Function of Laser Spot Size

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Rusby Dean

2018-01-01

Full Text Available The interaction of a high-intensity laser with a solid target produces an energetic distribution of electrons that pass into the target. These electrons reach the rear surface of the target creating strong electric potentials that act to restrict the further escape of additional electrons. The measurement of the angle, flux and spectra of the electrons that do escape gives insights to the initial interaction. Here, the escaping electrons have been measured using a differentially filtered image plate stack, from interactions with intensities from mid 1020-1017 W/cm2, where the intensity has been reduced by defocussing to increase the size of the focal spot. An increase in electron flux is initially observed as the intensity is reduced from 4x1020 to 6x1018 W/cm2. The temperature of the electron distribution is also measured and found to be relatively constant. 2D particle-in-cell modelling is used to demonstrate the importance of pre-plasma conditions in understanding these observations.

BRAF mutation testing in solid tumors: a methodological comparison.

Science.gov (United States)

Weyant, Grace W; Wisotzkey, Jeffrey D; Benko, Floyd A; Donaldson, Keri J

2014-09-01

Solid tumor genotyping has become standard of care for the characterization of proto-oncogene mutational status, which has traditionally been accomplished with Sanger sequencing. However, companion diagnostic assays and comparable laboratory-developed tests are becoming increasingly popular, such as the cobas 4800 BRAF V600 Mutation Test and the INFINITI KRAS-BRAF assay, respectively. This study evaluates and validates the analytical performance of the INFINITI KRAS-BRAF assay and compares concordance of BRAF status with two reference assays, the cobas test and Sanger sequencing. DNA extraction from FFPE tissue specimens was performed followed by multiplex PCR amplification and fluorescent label incorporation using allele-specific primer extension. Hybridization to a microarray, signal detection, and analysis were then performed. The limits of detection were determined by testing dilutions of mutant BRAF alleles within wild-type background DNA, and accuracy was calculated based on these results. The INFINITI KRAS-BRAF assay produced 100% concordance with the cobas test and Sanger sequencing and had sensitivity equivalent to the cobas assay. The INFINITI assay is repeatable with at least 95% accuracy in the detection of mutant and wild-type BRAF alleles. These results confirm that the INFINITI KRAS-BRAF assay is comparable to traditional sequencing and the Food and Drug Administration-approved companion diagnostic assay for the detection of BRAF mutations. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Bone-and-muscle-equivalent solid chemical dose meters for photon and electron doses above one kilorad

International Nuclear Information System (INIS)

McLaughlin, W.L.; Rosenstein, M.; Levine, H.

1975-01-01

Conventional solid dose meters, such as plastic films, powders, emulsions, glasses, ceramics and gels, have a response to ionizing photons and electrons that varies markedly over a broad spectrum when compared with the absorption characteristics of biological tissues. New radiochromic dyed plastic dose meters have been developed with X- and gamma ray and electron energy absorption cross-sections (calculated) and radiation energy responses (experimental) corresponding approximately to those for human muscle and bone, for a spectrum from a few keV to at least 10 MeV. Three-dimensional solid dose meters useful over the absorbed dose range of 10 3 to 10 6 rad are formed by thermosetting a selected combination of monomers containing the radiochromic dye in solution. Thin-film dose meters for the dose range 10 5 to 10 7 rad are formed by casting on optically flat surfaces strippable layers of special combinations of polymers and dyes in solution. The response of these systems to X- and gamma rays and electrons has been studied over various radiation spectra, dose-rates and temperatures during irradiation. (author)

Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors.

Science.gov (United States)

Smith, Tyrel T; Moffett, Howell F; Stephan, Sirkka B; Opel, Cary F; Dumigan, Amy G; Jiang, Xiuyun; Pillarisetty, Venu G; Pillai, Smitha P S; Wittrup, K Dane; Stephan, Matthias T

2017-06-01

Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.

Evaluation of apoptosis and micronucleation induced by reactor neutron beams with two different cadmium ratios in total and quiescent cell populations within solid tumors

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Sakurai, Yoshinori; Takagaki, Masao; Kobayashi, Tooru; Kinashi, Yuko; Suzuki, Minoru

2001-01-01

Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to reactor neutron beam irradiation with two different cadmium (Cd) ratios was examined in terms of micronucleus (MN) frequency and apoptosis frequency, using four different tumor cell lines. Methods and Materials: C57BL mice bearing EL4 tumors, C3H/He mice bearing SCC VII or FM3A tumors, and Balb/c mice bearing EMT6/KU tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty min after i.p. injection of sodium borocaptate- 10 B (BSH), or 3 h after oral administration of p-boronophenylalanine- 10 B (BPA), the tumors were irradiated with neutron beams. The tumors without 10 B-compound administration were irradiated with neutron beams or γ-rays. This neutron beam irradiation was performed using neutrons with two different Cd ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the MN frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, for apoptosis assay, 6 h after irradiation, tumor cell suspensions obtained in the same manner were fixed, and the apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequencies in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: Without 10 B-compounds, the sensitivity difference between total and Q cells was reduced by neutron beam irradiation. Under our particular neutron beam irradiation condition, relative biological effectiveness (RBE) of neutrons was larger in Q cells than in total cells, and the RBE values were larger for low Cd-ratio than high Cd-ratio neutrons. With 10 B-compounds, both frequencies were increased for each cell population, especially for total cells. BPA

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors.

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Trigos, Anna S; Pearson, Richard B; Papenfuss, Anthony T; Goode, David L

2017-06-13

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

OpenAIRE

Dirix, Luc Y.; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E.; Somer, Robert; Smakal, Martin; Emens, Leisha A.; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja

2017-01-01

Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 week...

Solid-state physics for electronics

National Research Council Canada - National Science Library

Moliton, André

2009-01-01

... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2. Quantum mechanics: some basics . . . . . . . . . . . . . . . . . . . . . . 1.2.1. The wave equation in solids: from Maxwell's to Schrödinger's equation via...

Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

International Nuclear Information System (INIS)

Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

2012-01-01

The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction.

NARCIS (Netherlands)

Brok, M.H.M.G.M. den; Nierkens, S.; Wagenaars, J.A.L.; Ruers, T.J.M.; Schrier, C.C.; Rijke, E.O.; Adema, G.J.

2012-01-01

Today's most commonly used microbial vaccines are essentially composed of antigenic elements and a non-microbial adjuvant, and induce solid amounts of antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which require cross-presentation of tumor-derived antigens by dendritic

Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors

Directory of Open Access Journals (Sweden)

Jappe Annette

2011-01-01

Full Text Available Abstract Background This phase I, randomized, multicenter, open-label study investigated the pharmacokinetics, safety, and efficacy of the oral mammalian target of rapamycin inhibitor everolimus in Chinese patients with advanced solid tumors. Methods A total of 24 patients with advanced breast cancer (n = 6, gastric cancer (n = 6, non-small cell lung cancer (n = 6, or renal cell carcinoma (n = 6 who were refractory to/unsuitable for standard therapy were randomized 1:1 to oral everolimus 5 or 10 mg/day. Primary end points were pharmacokinetic parameters and safety and tolerability. Pharmacokinetic 24-h profiles were measured on day 15; trough level was measured on days 2, 8, 15, 16, and 22. Tolerability was assessed continuously. This final analysis was performed after all patients had received 6 months of study drug or had discontinued. Results Everolimus was absorbed rapidly; median Tmax was 3 h (range, 1-4 and 2 h (range, 0.9-6 in the 5 and 10 mg/day groups, respectively. Pharmacokinetic parameters increased dose proportionally from the 5 and 10 mg/day doses. Steady-state levels were achieved by day 8 or earlier. The most common adverse events suspected to be related to everolimus therapy were increased blood glucose (16.7% and 41.7% and fatigue (16.7% and 33.3% in the everolimus 5 and 10 mg/day dose cohorts, respectively. Best tumor response was stable disease in 10 (83% and 6 (50% patients in the 5 and 10 mg/day groups, respectively. Conclusions Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies. Trial registration Chinese Health Authorities 2008L09346

Radiation- and Photo-induced Activation of 5-Fluorouracil Prodrugs as a Strategy for the Selective Treatment of Solid Tumors

Directory of Open Access Journals (Sweden)

Sei-ichi Nishimoto

2008-10-01

Full Text Available 5-Fluorouracil (5-FU is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that are tumor selective in their delivery and can be activated to improve the clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and ionizing radiation can cause chemical reactions in a localized area of the body, and these have been applied in the development of site-specific drug activation and sensitization. In this review, we describe recent progress in the development of novel 5-FU prodrugs that are activated site specifically by UV light and ionizing radiation in the tumor microenvironment. We also discuss the chemical mechanisms underlying this activation.

Detection of tumor-specific cytotoxic drug activity in vitro using the fluorometric microculture cytotoxicity assay and primary cultures of tumor cells from patients.

Science.gov (United States)

Nygren, P; Fridborg, H; Csoka, K; Sundström, C; de la Torre, M; Kristensen, J; Bergh, J; Hagberg, H; Glimelius, B; Rastad, J

1994-03-01

The semi-automated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) by viable cells, was employed for cytotoxic drug sensitivity testing of tumor cells from patients with hematological or solid tumors. In total, 390 samples from 20 diagnoses were tested with up to 12 standard cytotoxic drugs. The technical success rate for different tumor types ranged from 67 to 95%. Fluorescence was linearly related to cell number but variably steep depending on tumor type. Samples from most solid tumors thus showed higher signal-to-noise ratios than hematological samples. A wide spectrum of in vitro drug activity was obtained, with acute leukemias and non-Hodgkin's lymphomas being sensitive to almost all tested drugs, whereas renal and adrenocortical carcinomas were essentially totally resistant. Between these extremes were samples of breast and ovarian carcinomas and sarcomas. When in vitro response was compared with known clinical response patterns, a good correspondence was observed. The results indicate that the FMCA is a rapid and efficient method for in vitro measurement of tumor-specific drug activity both in hematological and in solid tumors. The assay may be suitable for new drug development and direction of phase-2 trials to suitable patients.

Thomson scattering from near-solid density plasmas using soft x-ray free electron lasers

Energy Technology Data Exchange (ETDEWEB)

Holl, A; Bornath, T; Cao, L; Doppner, T; Dusterer, S; Forster, E; Fortmann, C; Glenzer, S H; Gregori, G; Laarmann, T; Meiwes-Broer, K H; Przystawik, A; Radcliffe, P; Redmer, R; Reinholz, H; Ropke, G; Thiele, R; Tiggesbaumker, J; Toleikis, S; Truong, N X; Tschentscher, T; Uschmann, I; Zastrau, U

2006-11-21

We propose a collective Thomson scattering experiment at the VUV free electron laser facility at DESY (FLASH) which aims to diagnose warm dense matter at near-solid density. The plasma region of interest marks the transition from an ideal plasma to a correlated and degenerate many-particle system and is of current interest, e.g. in ICF experiments or laboratory astrophysics. Plasma diagnostic of such plasmas is a longstanding issue. The collective electron plasma mode (plasmon) is revealed in a pump-probe scattering experiment using the high-brilliant radiation to probe the plasma. The distinctive scattering features allow to infer basic plasma properties. For plasmas in thermal equilibrium the electron density and temperature is determined from scattering off the plasmon mode.

Solid pseudopapillary tumor of the pancreas (SPPT: Still an unsolved enigma Tumor sólido pseudopapilar del páncreas (TSSP: un enigma sin resolver

Directory of Open Access Journals (Sweden)

J. A. Cienfuegos

2010-12-01

Full Text Available Solid pseudo-papillary tumor (SPPT is a rare cystic tumor of the pancreas (1-3% of exocrine tumors of the pancreas which shows an "enigmatic" behavior on the clinical and molecular pattern. A retrospective analysis of the citological studies and resected specimens of pancreatic cystic tumors from May 1996 to February 2010 was carried out. Three cases of SPPT were found, which are the objective of this study. The diagnosis was established upon occasional finding in the abdominal CT, in spite of sizing between 3 and 6 cm of diameter. In the three cases the preoperative diagnosis was confirmed by citology and specific immunohistochemical staining. Cases 2 and 3 showed strong immunoreactivity for Beta-Catenina and E-Cadherina staining. Radical resection (R0 was carried out in the three cases. A young male -21 years of age (case 1- who had duodenal infiltration and two lymph nodes metastases died of hepatic and peritoneal recurrence 20 months following surgery. The other two cases are free of disease. The current review of the literature reports roughly 800 cases since the first report in 1959, and shows the enigmatic character of this tumor regarding the cellular origin, molecular pathways, prognostic factors and clinical behavior.El tumor pseudopapilar (TSPP es un tumor quístico del páncreas muy poco frecuente (1-3% de los tumores exocrinos del páncreas y que tiene un comportamiento oncológico y molecular "enigmático". Se realizó un análisis retrospectivo de las citologías de las lesiones quísticas del páncreas, así como de los tumores quísticos resecados entre mayo de 1996 y febrero de 2010, encontrándose tres tumores SSPP, motivo de este estudio. En los tres casos el diagnóstico fue ocasional en el TC abdominal a pesar de presentar unos tamaños entre 3 y 6 cm de diámetro. En los tres casos se confirmó el diagnóstico preoperatorio mediante citología e inmunohistoquímica. En los casos 2 y 3 se confirmó la positividad para Beta

Recurrent pancreatitis in pregnancy after preconception Whipple for pseudopapillary pancreatic tumor.

Science.gov (United States)

Dray, Danielle; Dahlke, Joshua D; Rouse, Dwight J

2014-08-01

Solid pseudopapillary pancreatic tumor is a rare tumor affecting young women. Case reports have presented pregnancy outcomes after pancreaticoduodenectomy (Whipple procedure) in pregnancy for this neoplasm. We report a case of a woman who underwent a preconception Whipple procedure for a solid pseudopapillary pancreatic tumor who experienced recurrent pancreatitis confined to pregnancy. A 28-year-old gravida 2 para 1 woman with a history of a Whipple procedure for a solid pseudopapillary pancreatic tumor 2 years prior had three episodes of severe pancreatitis in pregnancy. She was managed conservatively with each episode. She delivered at term and did not have a recurrence in the 8 months since her delivery. Recurrent pancreatitis in pregnancy after a preconception Whipple procedure can be managed conservatively without surgical intervention.

Amplification of tumor inducing putative cancer stem cells (CSCs) by vitamin A/retinol from mammary tumors

Energy Technology Data Exchange (ETDEWEB)

Sharma, Rohit B. [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States); Wang, Qingde [Department of Surgery, University of Pittsburgh, PA 15261 (United States); Khillan, Jaspal S., E-mail: khillan@pitt.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh, PA 15261 (United States)

2013-07-12

Highlights: •Vitamin A supports self renewal of putative CSCs from mammary tumors. •These cells exhibit impaired retinol metabolism into retinoic acid. •CSCs from mammary tumors differentiate into mammary specific cell lineages. •The cells express mammary stem cell specific CD29 and CD49f markers. •Putative CSCs form highly metastatic tumors in NOD SCID mouse. -- Abstract: Solid tumors contain a rare population of cancer stem cells (CSCs) that are responsible for relapse and metastasis. The existence of CSC however, remains highly controversial issue. Here we present the evidence for putative CSCs from mammary tumors amplified by vitamin A/retinol signaling. The cells exhibit mammary stem cell specific CD29{sup hi}/CD49f{sup hi}/CD24{sup hi} markers, resistance to radiation and chemo therapeutic agents and form highly metastatic tumors in NOD/SCID mice. The cells exhibit indefinite self renewal as cell lines. Furthermore, the cells exhibit impaired retinol metabolism and do not express enzymes that metabolize retinol into retinoic acid. Vitamin A/retinol also amplified putative CSCs from breast cancer cell lines that form highly aggressive tumors in NOD SCID mice. The studies suggest that high purity putative CSCs can be isolated from solid tumors to establish patient specific cell lines for personalized therapeutics for pre-clinical translational applications. Characterization of CSCs will allow understanding of basic cellular and molecular pathways that are deregulated, mechanisms of tumor metastasis and evasion of therapies that has direct clinical relevance.

Reinventing solid state electronics: Harnessing quantum confinement in bismuth thin films

Science.gov (United States)

Gity, Farzan; Ansari, Lida; Lanius, Martin; Schüffelgen, Peter; Mussler, Gregor; Grützmacher, Detlev; Greer, J. C.

2017-02-01

Solid state electronics relies on the intentional introduction of impurity atoms or dopants into a semiconductor crystal and/or the formation of junctions between different materials (heterojunctions) to create rectifiers, potential barriers, and conducting pathways. With these building blocks, switching and amplification of electrical currents and voltages are achieved. As miniaturisation continues to ultra-scaled transistors with critical dimensions on the order of ten atomic lengths, the concept of doping to form junctions fails and forming heterojunctions becomes extremely difficult. Here, it is shown that it is not needed to introduce dopant atoms nor is a heterojunction required to achieve the fundamental electronic function of current rectification. Ideal diode behavior or rectification is achieved solely by manipulation of quantum confinement using approximately 2 nm thick films consisting of a single atomic element, the semimetal bismuth. Crucially for nanoelectronics, this approach enables room temperature operation.

Solid intraocular xanthogranuloma in three Miniature Schnauzer dogs.

Science.gov (United States)

Zarfoss, Mitzi K; Dubielzig, Richard R

2007-01-01

Macrophages that contain abundant intracytoplasmic lipid are called 'foam cells'. In four canine globes submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW), foam cells formed a solid intraocular mass. The purpose of this study was to describe the histopathologic findings in these cases. The electronic COPLOW database (1993-2006) was searched for the diagnosis of 'foam cell tumor'. Clinical history, gross pathology and histopathology (5-micron sections, hematoxylin and eosin and Alcian blue periodic acid Schiff) were reviewed in all cases. Cases were included if the globe was grossly filled by a solid mass and if all intraocular structures were effaced by lipid-laden foam cell macrophages admixed with birefringent, Alcian blue-positive crystals oriented in stellate patterns. All three patients (four globes) satisfying the selection criteria were Miniature Schnauzers. In all cases the clinical history included diabetes mellitus, hyperlipidemia and chronic bilateral uveitis that was interpreted to be lens-induced. All globes were enucleated because of glaucoma. The term solid intraocular xanthogranuloma was used to describe these cases because the intraocular contents were effaced by a solid mass of foam cells and birefringent crystals. The cases in this report suggest that diabetic Miniature Schnauzers with hyperlipidemia are at risk for lipid and macrophage-rich uveitis, which may in some cases form a solid inflammatory intraocular mass, precipitate glaucoma, and lead to enucleation.

Ranges, Reflection and Secondary Electron Emission for keV Hydrogen Ions Incident on Solid N2

DEFF Research Database (Denmark)

Børgesen, P.; Sørensen, H.; Hao-Ming, Chen

1983-01-01

Ranges were measured for 0.67–3.3 keV/amu hydrogen and deuterium ions in solid N2. Comparisons with similar results for N2-gas confirm the previously observed large phase effect in the stopping cross section. Measurements of the secondary electron emission coefficient for bulk solid N2 bombarded...... by 0.67–9 keV/amu ions also seem to support such a phase effect. It is argued that we may also extract information about the charge state of reflected projectiles....

A low temperature cryostat with a refrigerator for studying electron-irradiation effects on solids, 2

International Nuclear Information System (INIS)

Oka, Takashi; Yoshida, Toshio; Shono, Yoshihiko

1978-01-01

A convenient cryostat with a small cryogenic refrigerator for studying electron-irradiation effects on solids is reported. The lowest temperature at the sample room is about 10 K or less. In a temperature region below 80 K, the sample temperature can be controlled within 0.05 K. (auth.)