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Sample records for therapy tumor change

  1. Ultrastructural changes in tumor cells following boron neutron capture therapy

    International Nuclear Information System (INIS)

    Barkla, D.H.; Brown, J.K.; Meriaty, H.; Allen, B.J.

    1992-01-01

    In a previous study the authors reported on morphological changes in two human melanoma cell lines treated with 10 B-phenylalanine(BPA) and Boron Neutron Capture Therapy(BNCT). The present study describes morphological changes in melanoma and glioma cell lines treated with boron-tetraphenyl porphyrin(BTPP) and BNCT. Porphyrin compounds are selectively taken up by tumor cells and have been used clinically in phototherapy treatment of cancer patients. Boronated porphyrins show good potential as therapeutic agents in BNCT treatment of human cancer patients

  2. Forecasting longitudinal changes in oropharyngeal tumor morphology throughout the course of head and neck radiation therapy

    International Nuclear Information System (INIS)

    Yock, Adam D.; Kudchadker, Rajat J.; Rao, Arvind; Dong, Lei; Beadle, Beth M.; Garden, Adam S.; Court, Laurence E.

    2014-01-01

    Purpose: To create models that forecast longitudinal trends in changing tumor morphology and to evaluate and compare their predictive potential throughout the course of radiation therapy. Methods: Two morphology feature vectors were used to describe 35 gross tumor volumes (GTVs) throughout the course of intensity-modulated radiation therapy for oropharyngeal tumors. The feature vectors comprised the coordinates of the GTV centroids and a description of GTV shape using either interlandmark distances or a spherical harmonic decomposition of these distances. The change in the morphology feature vector observed at 33 time points throughout the course of treatment was described using static, linear, and mean models. Models were adjusted at 0, 1, 2, 3, or 5 different time points (adjustment points) to improve prediction accuracy. The potential of these models to forecast GTV morphology was evaluated using leave-one-out cross-validation, and the accuracy of the models was compared using Wilcoxon signed-rank tests. Results: Adding a single adjustment point to the static model without any adjustment points decreased the median error in forecasting the position of GTV surface landmarks by the largest amount (1.2 mm). Additional adjustment points further decreased the forecast error by about 0.4 mm each. Selection of the linear model decreased the forecast error for both the distance-based and spherical harmonic morphology descriptors (0.2 mm), while the mean model decreased the forecast error for the distance-based descriptor only (0.2 mm). The magnitude and statistical significance of these improvements decreased with each additional adjustment point, and the effect from model selection was not as large as that from adding the initial points. Conclusions: The authors present models that anticipate longitudinal changes in tumor morphology using various models and model adjustment schemes. The accuracy of these models depended on their form, and the utility of these models

  3. Combined tumor therapy

    International Nuclear Information System (INIS)

    Wrba, H.

    1990-01-01

    This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs [de

  4. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  5. Radiation therapy of brain tumor

    International Nuclear Information System (INIS)

    Sung, K. J.; Lee, D. H.; Park, C. Y.

    1980-01-01

    One hundred and six cases of brain tumors were treated at the Yonsei Cancer Center from January 1972 to August 1978 by Co-60 teletherapy unit. We analyses their clinical findings, histopathological findings, treatment and results. In those cases which computerized tomography had been used before and after radiation therapy, changes in tumor size and the presence of edema or necrosis following treatment was evaluated. 1. Among 106 cases, 90 cases were primary brain tumors and 16 cases were metastatic brain tumors. Pituitary tumors (38), glioma (34) and pinealoma (10) composed of most of primary brain tumors. 2. Post treatment follow-up was possible in 38 cases more than 1 years. Four among 11 cases of giloma expired and survivors had considerable neurological symptoms except 2 cases. Sixty five percent (12/20) of pituitary tumors showed improvement of visual symptoms and all cases (7) of pinealoma which post treatment follow-up was possible, showed remarkable good response. 3. Findings of CT scan after radiation treatment were compatible with results of clinical findings and post treatment follow-up. It showed complete regression of tumor mass in one case of pinealoma and medulloblastoma. One case of pituitary tumor showed almost complete regression of tumor mass. It also showed large residual lesion in cases of glioblastoma multiforme and cystic astrocytoma.

  6. Changes in tumor cell response due to prolonged dose delivery times in fractionated radiation therapy

    International Nuclear Information System (INIS)

    Paganetti, Harald

    2005-01-01

    Purpose: Dynamic radiation therapy, such as intensity-modulated radiation therapy, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The cellular damage after a full treatment may depend on the dose rate, because sublethal radiation damage can be repaired more efficiently during prolonged dose delivery. The goal of this study was to investigate the significance of this effect in fractionated radiation therapy. Methods and Materials: The lethal/potentially lethal model was used to calculate lesion induction rates for repairable and nonrepairable lesions. Dose rate effects were analyzed for 9 different cell lines (8 human tumor xenografts and a C3H10T1/2 cell line). The effects of single-fraction as well as fractionated irradiation for different dose rates were studied. Results: Significant differences can be seen for dose rates lower than about 0.1 Gy/min for all cell lines considered. For 60 Gy delivered in 30 fractions, the equivalent dose is reduced by between 1.3% and 12% comparing 2 Gy delivery over 30 min per fraction with 2 Gy delivery over 1 min per fraction. The effect is higher for higher doses per fraction. Furthermore, the results show that dose rate effects do not show a simple correlation with the α/β ratio for ratios between 3 Gy and 31 Gy. Conclusions: If the total dose delivery time for a treatment fraction in radiation therapy increases to about 20 min, a correction for dose rate effects may have to be considered in treatment planning. Adjustments in effective dose may be necessary when comparing intensity-modulated radiation therapy with conventional treatment plans

  7. Experimental tumor therapy

    International Nuclear Information System (INIS)

    1982-06-01

    This is a report on the work of the joint research group of the Institute of Radiation Biology (Strahlenbiologisches Institut) of the university of Munich and the Department of Radiation Biology of the Society for Radiation and Environmental Research (Gesellschaft fuer Strahlen- u. Umweltforschung - GSF -) at Neuherberg. The presented results are not in all cases definitely confirmed or have, in part, merely provisional character. It is the target of the joint research to investigate problems of cancer therapy of practical impact in model form and to develop recommendations in discussions with therapists. Thus, the aim is not so much to examine mechanisms of action of certain radiations in detail but to look for the general rules they are governed by and to analyze the quantitative aspects of cancer therapy. To achieve this, a great variety of test models must be at hand. Numerous cell cultivies and tumors of mice resp. rats are therefore used. The acute reactions to irradiation are examined on the skin, the small intestine crypts, the bone marrow and spleen colonies of mice and the chronic reactions are tested on the colon and heart of rats and on the vascular connective tissue and kidneys of mice. (orig./MG) [de

  8. Proton Therapy for Thoracoabdominal Tumors

    Science.gov (United States)

    Sakurai, Hideyuki; Okumura, Toshiyuki; Sugahara, Shinji; Nakayama, Hidetsugu; Tokuuye, Koichi

    In advanced-stage disease of certain thoracoabdominal tumors, proton therapy (PT) with concurrent chemotherapy may be an option to reduce side effects. Several technological developments, including a respiratory gating system and implantation of fiducial markers for image guided radiation therapy (IGRT), are necessary for the treatment in thoracoabdominal tumors. In this chapter, the role of PT for tumors of the lung, the esophagus, and liver are discussed.

  9. Brain Tumor Therapy-Induced Changes in Normal-Appearing Brainstem Measured With Longitudinal Diffusion Tensor Imaging

    International Nuclear Information System (INIS)

    Hua Chiaho; Merchant, Thomas E.; Gajjar, Amar; Broniscer, Alberto; Zhang, Yong; Li Yimei; Glenn, George R.; Kun, Larry E.; Ogg, Robert J.

    2012-01-01

    Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4–39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54–59.4 Gy). Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6–5.0 years). The median mean dose to the pons was 56 Gy (range, 7–59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response

  10. Regional Lung Density Changes After Radiation Therapy for Tumors in and Around Thorax

    International Nuclear Information System (INIS)

    Ma Jinli; Zhang Junan; Zhou Sumin; Hubbs, Jessica L.; Foltz, Rodney J.; Hollis, Donna R.; Light, Kim L.; Wong, Terence Z.; Kelsey, Christopher R.; Marks, Lawrence B.

    2010-01-01

    Purpose: To study the temporal nature of regional lung density changes and to assess whether the dose-dependent nature of these changes is associated with patient- and treatment-associated factors. Methods and Materials: Between 1991 and 2004, 118 patients with interpretable pre- and post-radiation therapy (RT) chest computed tomography (CT) scans were evaluated. Changes in regional lung density were related to regional dose to define a dose-response curve (DRC) for RT-induced lung injury using three-dimensional planning tools and image fusion. Multiple post-RT follow-up CT scans were evaluated by fitting linear-quadratic models of density changes on dose with time as the covariate. Various patient- and treatment-related factors were examined as well. Results: There was a dose-dependent increase in regional lung density at nearly all post-RT follow-up intervals. The population volume-weighted changes evolved over the initial 6-month period after RT and reached a plateau thereafter (p < 0.001). On univariate analysis, patient age greater than 65 years (p = 0.003) and/or the use of pre-RT surgery (p < 0.001) were associated with significantly greater changes in CT density at both 6 and 12 months after RT, but the magnitude of this effect was modest. Conclusions: There appears to be a temporal nature for the dose-dependent increases in lung density. Nondosimetric clinical factors tend to have no, or a modest, impact on these changes.

  11. Therapy of malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Jellinger, K [ed.

    1987-01-01

    The tumors of the brain claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper dis-posability for rational management and therapeutic strategies. The primary aim of the present book is to serve these purposes. With 8 chapters, two of them are indexed for INIS, the collective of competent authors deal on the biology, pathology and immunology of malignant brain tumors of adults and of children including relevant basic and recent data of experimental research; further on the available methods of therapy: neurosurgery, radiology and chemotherapy, the fundamental principals of their efficacy and the differing models of single respective combined application, in comprehensive critical form. 111 figs.

  12. Therapy of malignant brain tumors

    International Nuclear Information System (INIS)

    Jellinger, K.

    1987-01-01

    The tumors of the brain claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper dis-posability for rational management and therapeutic strategies. The primary aim of the present book is to serve these purposes. With 8 chapters, two of them are indexed for INIS, the collective of competent authors deal on the biology, pathology and immunology of malignant brain tumors of adults and of children including relevant basic and recent data of experimental research; further on the available methods of therapy: neurosurgery, radiology and chemotherapy, the fundamental principals of their efficacy and the differing models of single respective combined application, in comprehensive critical form. 111 figs

  13. Radiation therapy for digestive tumors

    International Nuclear Information System (INIS)

    Piedbois, P.; Levy, E.; Thirion, P.; Martin, L.; Calitchi, E.; Otmezguine, Y.; Le Bourgeois, J.P.

    1995-01-01

    This brief review of radiation therapy of digestive tumors in 1994 seeks to provide practical answers to the most commonly asked questions: What is the place of radiation therapy versus chemotherapy for the treatment of these patients ? What are the approved indications of radiation therapy and which avenues of research are being explored ? Radiation therapy is used in over two-thirds of patients referred to an oncology department for a gastrointestinal tract tumor. The main indications are reviewed: cancer of the rectum and anal canal and, to a lesser extent, cancer of the esophagus and pancreas. The main focuses of current research include radiation therapy-chemotherapy combinations, intraoperative radiation therapy, and radiation therapy of hepatobiliary tumors. (authors). 23 refs., 1 fig

  14. Which drug or drug delivery system can change clinical practice for brain tumor therapy?

    OpenAIRE

    Siegal, Tali

    2013-01-01

    The prognosis and treatment outcome for primary brain tumors have remained unchanged despite advances in anticancer drug discovery and development. In clinical trials, the majority of promising experimental agents for brain tumors have had limited impact on survival or time to recurrence. These disappointing results are partially explained by the inadequacy of effective drug delivery to the CNS. The impediments posed by the various specialized physiological barriers and active efflux mechanis...

  15. Tumor therapy and pregnancy

    International Nuclear Information System (INIS)

    Joss, R.; Brunner, K.W.

    1982-01-01

    Many successfully treated tumour patients are children and juveniles. This raises questions as to the effects of tumour therapy on reproductiveness and offspring. The possible extent of damage to the male and female gonads caused by surgical, chemical, and radiological tumour therapy is investigated. Also, the problem of tumour therapy or women developing neoplasms during pregnancy. Pregnancies after successful tumour therapy are quite frequent today. Experience so far suggests that the rate of congenital deformities is not significantly increased. (orig.) [de

  16. Tumor therapy evaluation

    International Nuclear Information System (INIS)

    Blattmann, H.; Kaser-Hotz, B.; Parvis, A.

    1997-01-01

    The aim of this program is to acquire data in order to evaluate the advantages of the proton spot scan technique compared to other forefront radiotherapy procedures, and to integrate the diagnostic and therapeutic possibilities of the life science department for human cancer therapy by testing it in veterinary radio-oncology. (author) 1 fig., 2 tab., 2 refs

  17. Multimodal OCT for complex assessment of tumors response to therapy

    Science.gov (United States)

    Sirotkina, Marina A.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Zaitsev, Vladimir Yu.; Matveyev, Alexander L.; Shirmanova, Marina V.; Sovetsky, Alexander A.; Moiseev, Alexander A.; Zagaynova, Elena V.; Vitkin, Alex; Gladkova, Natalia D.

    2017-07-01

    Multimodal OCT is a promising tool for monitoring of individual tumor response to antitumor therapies. The changes of tumor cells, connective tissue, microcirculation and stiffness can be estimated simultaneously in real time with high resolution.

  18. Radiological changes of bones and soft tissues after irradiation therapy in patients with Wilms' tumor and neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Hiroaki; Okabe, Ikuo

    1989-04-01

    Late effects of tele cobalt 60 therapy on bones and soft tissues were studied radiologically in 24 patients with neuroblastoma and Wilms' tumor. The degree of changes in spinal bodies was influenced by the dose of irradiation as well as the age of patients at the time of irradiation. In patients who had 15 to 19 Gy of irradiation at the ages under one year old, a moderate to severe degree of changes was observed. Many patients showed atrophies of iliac bone, ribs, and erector spinae and psoas muscles on the side of the irradiation. In patients who were equal to or over 12 y.o. at the time of the examination, the degree of atrophy of erector spinae muscles on the side of the irradiation was greater than that of the patients who were less than 12 y.o.. Scoliosis was observed in 71% of patients and it had a tendency to aggravate at puberty. Because there was a significant correlation between the degree of scoliosis and the severity of the atrophic erector spinae muscle, the latter was thought to contribute much to the development of the former. At present, all patients are living with no limitation of their daily activities and no one needs medical care. (author).

  19. Experimental tumor therapy

    International Nuclear Information System (INIS)

    1980-01-01

    This study was concentrated on the investigation of practically oriented problems of tumour therapy, under the application of possibly differing experimental test subjects, ranging from cell cultures to the living animal. The development of the test systems was advanced and some systems were replaced by new ones. An enrichment of great significance is also the fibrosarcoma SSK-2 of the C3H mouse, whose cells form colonies with an exploitation of about 50% when the explant is transferred directly to the cell culture. The subject matter of the experiments ranged from the effect of irradiation on cells in vitro to the proliferation kinetics of human tumours under treatment. As in the last year the main significance and attention was attributed to the analysis of time dependency in radiotherapy. The second main point were investigations on the interaction of chemotherapy and radiotherapy, supplemented by experiments to the time dependency in chemotherapy. (orig./MG) [de

  20. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  1. Therapy-associated Solid Tumors

    International Nuclear Information System (INIS)

    Travis, Lois B.

    2002-01-01

    As survival after a diagnosis of cancer improves, characterization of the late sequelae of treatment becomes critical. The development of second malignant neoplasms represents one of the most serious side effects of treatment with radiation and chemotherapy. Although secondary leukemia was the first reported carcinogenic effect resulting from cancer treatment, solid tumors now comprise the largest second tumor burden in some populations of survivors. It should be recognized, however, that solid cancers do not necessarily represent an adverse effect of therapy, but may also reflect the operation of shared etiologic factors, host determinants, gene-environment interactions, and other influences. Quantification of second cancer risk is important in terms of patient management, enabling clinicians to make informed decisions with regard to optimal treatment of the initial cancer, balancing efficacy against acute and chronic sequelae. This article focuses on selected highlights and recent developments in treatment-associated solid malignancies, with emphasis on radiotherapy and chemotherapy in adults, and summarizes areas for future research. Although cancer therapy represents a double-edged sword, it should always be recognized that it is advances in treatment that are largely responsible for the tremendous improvement in patient survival. Thus, the benefit derived from many cancer therapies far outweighs any risk of developing a second cancer

  2. Deformable Image Registration for Adaptive Radiation Therapy of Head and Neck Cancer: Accuracy and Precision in the Presence of Tumor Changes

    International Nuclear Information System (INIS)

    Mencarelli, Angelo; Kranen, Simon Robert van; Hamming-Vrieze, Olga; Beek, Suzanne van; Nico Rasch, Coenraad Robert; Herk, Marcel van; Sonke, Jan-Jakob

    2014-01-01

    Purpose: To compare deformable image registration (DIR) accuracy and precision for normal and tumor tissues in head and neck cancer patients during the course of radiation therapy (RT). Methods and Materials: Thirteen patients with oropharyngeal tumors, who underwent submucosal implantation of small gold markers (average 6, range 4-10) around the tumor and were treated with RT were retrospectively selected. Two observers identified 15 anatomical features (landmarks) representative of normal tissues in the planning computed tomography (pCT) scan and in weekly cone beam CTs (CBCTs). Gold markers were digitally removed after semiautomatic identification in pCTs and CBCTs. Subsequently, landmarks and gold markers on pCT were propagated to CBCTs, using a b-spline-based DIR and, for comparison, rigid registration (RR). To account for observer variability, the pair-wise difference analysis of variance method was applied. DIR accuracy (systematic error) and precision (random error) for landmarks and gold markers were quantified. Time trend of the precisions for RR and DIR over the weekly CBCTs were evaluated. Results: DIR accuracies were submillimeter and similar for normal and tumor tissue. DIR precision (1 SD) on the other hand was significantly different (P<.01), with 2.2 mm vector length in normal tissue versus 3.3 mm in tumor tissue. No significant time trend in DIR precision was found for normal tissue, whereas in tumor, DIR precision was significantly (P<.009) degraded during the course of treatment by 0.21 mm/week. Conclusions: DIR for tumor registration proved to be less precise than that for normal tissues due to limited contrast and complex non-elastic tumor response. Caution should therefore be exercised when applying DIR for tumor changes in adaptive procedures

  3. Gene therapy and radiotherapy in malignant tumor

    International Nuclear Information System (INIS)

    Zhang Yaowen; Cao Yongzhen; Li Jin; Wang Qin

    2008-01-01

    Tumor treatment is one of the most important fields in medical research. Nowadays, a novel method which is combined gene therapy with radiotherapy plays an important role in the field of cancer research, and mainly includes immune gene therapy combined with radiotherapy, suicide gene therapy or tumor suppressor gene therapy combined with radiotherapy, antiangiogenesis gene therapy combined with radiotherapy and protective gene therapy combined with radiotherapy based on the technical features. This review summarized the current status of combined therapies of gene therapy and radiotherapy and possible mechanism. (authors)

  4. Radiation therapy of thoracic and abdominal tumors

    International Nuclear Information System (INIS)

    LaRue, S.M.; Gillette, S.M.; Poulson, J.M.

    1995-01-01

    Until recently, radiotherapy of thoracic and abdominal tumors in animals has been limited. However, the availability of computerized tomography and other imaging techniques to aid in determining the extent of tumor, an increase in knowledge of dose tolerance of regional organs, the availability of isocentrically mounted megavoltage machines, and the willingness of patients to pursue more aggressive treatment is making radiation therapy of tumors in these regions far more common. Tumor remission has been reported after radiation therapy of thymomas. Radiation therapy has been used to treat mediastinal lymphoma refractory to chemotherapy, and may be beneficial as part of the initial treatment regimen for this disease. Chemodectomas are responsive to radiation therapy in human patients, and favorable response has also been reported in dogs. Although primary lung tumors in dogs are rare, in some cases radiation therapy could be a useful primary or adjunctive therapy. Lung is the dose-limiting organ in the thorax. Bladder and urethral tumors in dogs have been treated using intraoperative and external-beam radiation therapy combined with chemotherapy. These tumors are difficult to control locally with surgery alone, although the optimal method of combining treatment modalities has not been established. Local control of malignant perianal tumors is also difficult to achieve with surgery alone, and radiation therapy should be used. Intraoperative radiation therapy combined with external-beam radiation therapy has been used for the management of metastatic carcinoma to the sublumbar lymph nodes. Tolerance of retroperitoneal tissues may be decreased by disease or surgical manipulation

  5. Oxygenation of spontaneous canine tumors during fractionated radiation therapy

    International Nuclear Information System (INIS)

    Achermann, R.E.; Ohlerth, S.M.; Bley, C.R.; Inteeworn, N.; Schaerz, M.; Wergin, M.C.; Kaser-Hotz, B.; Gassmann, M.; Roos, M.

    2004-01-01

    Background and purpose: tumor oxygenation predicts treatment outcome, and reoxygenation is considered important in the efficacy of fractionated radiation therapy. Therefore, the purpose of this study was to document the changes of the oxygenation status in spontaneous canine tumors during fractionated radiation therapy using polarographic needle electrodes. Material and methods: tumor oxygen partial pressure (pO 2 ) measurements were performed with the eppendorf-pO 2 -Histograph. The measurements were done under general anesthesia, and probe tracks were guided with ultrasound. pO 2 was measured before radiation therapy in all dogs. In patients treated with curative intent, measurements were done sequentially up to eight times (total dose: 45-59.5 Gy). Oxygenation status of the palliative patient group was examined before each fraction of radiation therapy up to five times (total dose: 24-30 Gy). Results: 15/26 tumors had a pretreatment median pO 2 ≤ 10 mmHg. The pO 2 values appeared to be quite variable in individual tumors during fractionated radiation therapy. The pO 2 of initially hypoxic tumors (pretreatment median pO 2 ≤ 10 mmHg) remained unchanged during fractionated radiotherapy, whereas in initially normoxic tumors the pO 2 decreased. Conclusion: hypoxia is common in spontaneous canine tumors, as 57.7% of the recorded values were ≥ 10 mmHg. The data of this study showed that initially hypoxic tumors remained hypoxic, whereas normoxic tumors became more hypoxic. (orig.)

  6. Imaging after radiation therapy of thoracic tumors

    International Nuclear Information System (INIS)

    Ghaye, B.; Wanet, M.; El Hajjam, M.

    2016-01-01

    Radiation-induced lung disease (RILD) is frequent after therapeutic irradiation of thoracic malignancies. Many technique-, treatment-, tumor- and patient-related factors influence the degree of injury sustained by the lung after irradiation. Based on the time interval after the completion of the treatment RILD presents as early and late features characterized by inflammatory and fibrotic changes, respectively. They are usually confined to the radiation port. Though the typical pattern of RILD is easily recognized after conventional two-dimensional radiation therapy (RT), RILD may present with atypical patterns after more recent types of three or four-dimensional RT treatment. Three atypical patterns are reported: the modified conventional, the mass-like and the scar-like patterns. Knowledge of the various features and patterns of RILD is important for correct diagnosis and appropriate treatment. RILD should be differentiated from recurrent tumoral disease, infection and radiation-induced tumors. Due to RILD, the follow-up after RT may be difficult as response evaluation criteria in solid tumours (RECIST) criteria may be unreliable to assess tumor control particularly after stereotactic ablation RT (SABR). Long-term follow-up should be based on clinical examination and morphological and/or functional investigations including CT, PET-CT, pulmonary functional tests, MRI and PET-MRI. (authors)

  7. Radiation Therapy of Suprasellar Germ Cell Tumors

    International Nuclear Information System (INIS)

    Park, Woo Yoon; Choi, Doo Ho; Choi, Eun Kyung; Kim, Il Han; Ha, Sung Whan; Park, Charn Il

    1988-01-01

    A retrospective study was performed on 15 patients with suprasellar germ cell tumors treated by megavoltage external beam irradiation between Feb. 1979 and Dec. 1985. Follow-up period of survivors was 30 to 91 months. Histologic diagnosis was obtained before radiation therapy in 10 patients (9 germinomas and 1 mixed). Five patients were treated without histologic verification. In 9 patients with biopsy-proven germinomas radiation therapy was delivered to the craniospinal axis in 6, to the whole brain in 3. In 5 patients with mixed germ cell tumor or elevated tumor marker, irradiation was delivered to the craniospinal axis in 2, to the whole brain in 2, and to the primary site only in 1. Total doses ranged from 5,000 to 5,500 cGy to the primary site, 3,000 to 4,400 cGy to the whole brain, and 1,300 to 3,000 cGy to the spine. In these 14, local tumor was controlled and primary or spinal failure was not observed. One patient without elevated tumor marker was treated to the whole brain, The tumor was not controlled and he had spinal recurrence. It is proven that radiation therapy is an effective treatment for suprasellar germ cell tumors. The neuroendocrinologic presentation, tumor marker status, early response to radiation measured on CT seem to be useful means for selecting patients for radiation therapy when tissue diagnosis is not available

  8. Therapy tumor with the heavy ions beam

    International Nuclear Information System (INIS)

    Dang Bingrong; Wei Zengquan; Li Wenjian

    2002-01-01

    As physical characteristic of heavy ions Bragg peak, therapy tumor with heavy ions is becoming advanced technology. So, many countries have developed the technology and used to treat tumor, the societal and economic effects are beneficial to people. The authors show the development, present situation and information of research in world of advanced radiotherapy with heavy ions

  9. Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Hong, Beom-Ju; Bok, Seoyeon; Lee, Chan-Ju; Kim, Young-Eun [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Jeon, Sang-Rok [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Yun-Sang [Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cheon, Gi Jeong; Paeng, Jin Chul [Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Carlson, David J. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); and others

    2016-07-01

    Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy. Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [{sup 18}F]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day −1), at 6 hours (day 0), and 2 (day 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed. Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 ± 0.483 at day −1, 1.67 ± 0.116 at day 0, 2.92 ± 0.334 at day 2, and 2.13 ± 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 co-immunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses. Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had decreased

  10. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...... the reader will gain: The review focuses on strategies that exploit characteristic features of solid tumors, such as abnormal vasculature, overexpression of receptors and enzymes, as well as acidic and thiolytic characteristics of the tumor microenvironment. Take home message: It is concluded that the design...

  11. Radiation therapy for metastatic spinal tumors

    International Nuclear Information System (INIS)

    Kida, Akio; Fukuda, Haruyuki; Taniguchi, Shuji; Sakai, Kazuaki

    2000-01-01

    The results of radiation therapy for metastatic spinal tumors were evaluated in terms of pain relief, improvement of neurological impairment, and survival. Between 1986 and 1995, 52 symptomatic patients with metastatic spinal tumors treated with radiation therapy were evaluated. The patients all received irradiation of megavoltage energy. Therapeutic efficacy was evaluated in terms of pain relief and improvement of neurological impairment. Pain relief was observed in 29 (61.7%) of 47 patients with pain. Therapy was effective for 17 (70.8%) of 24 patients without neurological impairment, and efficacy was detected in 12 (52.2%) of 23 patients with neurological impairment. Improvement of neurological symptoms was obtained in seven (25.0%) of 28 patients with neurological impairment. Radiation therapy was effective for pain relief in patients with metastatic spinal tumors. In patients with neurological impairment, less pain relief was observed than in those without impairment. Improvement of neurological impairment was restricted, but radiation therapy was thought to be effective in some cases in the early stage of neurological deterioration. Radiation therapy for metastatic spinal tumors contraindicated for surgery was considered effective for improvement of patients' activities of daily living. (author)

  12. 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.

  13. INTRAOPERATIVE PHOTODYNAMIC THERAPY FOR METASTATIC PERITONEAL TUMORS

    Directory of Open Access Journals (Sweden)

    E. A. Suleimanov

    2016-01-01

    Full Text Available This review is devoted to the cytoreductive treatment of malignant tumors of the abdominal organs. The actuality of the issue is determined both by increase of the incidence of abdominal cancer in Russia and in majority of developed countries and by high rate diagnosis on late stages of disease. The methods of treatment of peritoneal carcinomatosis, based on possible effects on the secondary peritoneal tumors after surgical cytoreduction to reduce the risk of local recurrence and disease progression are described. These methods of additional intraoperative specific antitumor action include intraoperative radiation therapy, hyperthermic intraperitoneal chemotherapy, intraoperative photodynamic therapy characterized by differences in difficulty of performance, mechanisms of effect on tumor and healthy tissues, efficiency. Benefits, opportunities and possibilities of application of intraoperative photodynamic therapy (IOPDT for secondary peritoneal tumors are described in details, the results of a number of domestic and foreign clinical studies are shown, the successful application of intraoperative photodynamic therapy in clinical oncology, which allows reducing the risk of secondary tumor lesions of the peritoneum significantly, is demonstrated. Photodynamic therapy – a method with high efficiency and almost no side effects and complications, based on the ability of photosensitizer to accumulate selectively and retain in the high proliferative tissues. The advantages of this type of treatment of patients with peritoneal carcinomatosis are a selective effect on the peritoneal carcinomatosis and on visually detected tumor tissue, high efficiency in patients with malignant tumors of the abdominal cavity and pelvis combined with surgical cytoreduction, minimal effect on normal organs and tissues of the patient, well tolerated procedure.

  14. Noncirrhotic portal fibrosis after Wilms' tumor therapy

    International Nuclear Information System (INIS)

    Barnard, J.A.; Marshall, G.S.; Neblett, W.W.; Gray, G.; Ghishan, F.K.

    1986-01-01

    A 9-yr-old girl developed massive hemorrhage from esophageal varices 2 yr after combined modality therapy for Wilms' tumor. Evaluation showed a patent extrahepatic portal venous system and an elevated splenic pulp pressure. In contrast to previous reports of hepatopathy after irradiation injury, histologic sections of the liver did not demonstrate occlusion of the central veins, but rather a diffuse obliteration of intrahepatic portal venous radicles. This pattern of noncirrhotic portal fibrosis has not been described following antitumor therapy

  15. Radiogenetic therapy: strategies to overcome tumor resistance.

    Science.gov (United States)

    Marples, B; Greco, O; Joiner, M C; Scott, S D

    2003-01-01

    The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and/or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or that exploit hypoxia, the most ubiquitous characteristic of most solid cancers. The goal of this review is to highlight two promising gene therapy methods developed specifically to target the tumor volume that can be readily used in combination with radiotherapy. The first approach uses radiation-responsive gene promoters to control the selective expression of a suicide gene (e.g., herpes simplex virus thymidine kinase) to irradiated tissue only, leading to targeted cell killing in the presence of a prodrug (e.g., ganciclovir). The second method utilizes oxygen-dependent promoters to produce selective therapeutic gene expression and prodrug activation in hypoxic cells, which are refractive to conventional radiotherapy. Further refining of tumor targeting can be achieved by combining radiation and hypoxia responsive elements in chimeric promoters activated by either and dual stimuli. The in vitro and in vivo studies described in this review suggest that the combination of gene therapy and radiotherapy protocols has potential for use in cancer care, particularly in cases currently refractory to treatment as a result of inherent or hypoxia-mediated radioresistance.

  16. Radiation Therapy of Pituitary Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Park, Moon Baik; Hong, Seong Eong [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

    1989-12-15

    Radiation treatment results were analyzed in a retrospective analysis of 47 patients with pituitary adenoma treated with radiation alone or combined with surgery from 1974 through 1987 at the Department of Therapeutic Radiology of Kyung Hee University. The 5-year overall survival rates for all patients was 80.4%. Radiation therapy was effective for improving visual symptoms and headache, but could not normalize amenorrhea and galactorrhoea. There was no difference of survival rate between radiation alone and combination with surgery. Prognostic factors such as age, sex, disease type, visual field, headache and surgical treatment were statistically no significant in survival rates of these patients.

  17. Radiation Therapy of Pituitary Tumors

    International Nuclear Information System (INIS)

    Park, Moon Baik; Hong, Seong Eong

    1989-01-01

    Radiation treatment results were analyzed in a retrospective analysis of 47 patients with pituitary adenoma treated with radiation alone or combined with surgery from 1974 through 1987 at the Department of Therapeutic Radiology of Kyung Hee University. The 5-year overall survival rates for all patients was 80.4%. Radiation therapy was effective for improving visual symptoms and headache, but could not normalize amenorrhea and galactorrhoea. There was no difference of survival rate between radiation alone and combination with surgery. Prognostic factors such as age, sex, disease type, visual field, headache and surgical treatment were statistically no significant in survival rates of these patients

  18. Diagnosis and therapy of spinal tumors

    International Nuclear Information System (INIS)

    Algra, P.R.; Valk, J.; Heimans, J.J.

    1998-01-01

    Many different opinions exist as to the appropriate diagnostic workup and therapy for spinal tumors. With the advent of new imaging techniques and therapeutic regimens, an up-to-date reference work has become an urgent requirement. This book is designed to meet this need, and is the first of its kind to offer an overview of the opinions of internationally renowned specialists in the field. By addressing in detail all of the relevant topics and areas of contention, it should prove of great value in establishing rational imaging and therapeutic protocols for spinal tumors. (orig.)

  19. Value of PET and PET-CT for monitoring tumor therapy

    International Nuclear Information System (INIS)

    Chen Xiang; Zhao Jinhua

    2007-01-01

    18 F-fluorodeoxyglucose ( 18 F-FDG) PET or PET-CT is an accurate test for differentiating residual viable tumor tissue from therapy-induced changes in tumor. Furthermore, quantitative assessment of therapy-induced changes in tumor 18 F-FDG uptake may allow the prediction of tumor response. Treatment may be adjusted according to tumor response. So it is increasingly used to monitor tumor response in patients undergoing chemotherapy and chemoradiotherapy. Here we focused on practical aspects of 18 F-FDG PET or PET-CT for treatment monitoring and on the existing advantages and challenges. (authors)

  20. Genetic changes of two Wilms tumors with anaplasia and a review of the literature suggesting a marker profile for therapy resistance.

    Science.gov (United States)

    Stock, Cornelia; Ambros, Inge M; Lion, Thomas; Zoubek, Andreas; Amann, Gabriele; Gadner, Helmut; Ambros, Peter F

    2002-06-01

    Cytogenetic data on Wilms tumors (WT) with anaplasia frequently associated with an unfavorable outcome are scarce. We present cytogenetic changes of two WT with anaplasia (primary tumor material) from nonresponders with a synopsis of the literature. The WT were investigated by cytogenetic analysis, comparative genomic hybridization, fluorescence in situ hybridization, immunofluorescence, and flow cytometric analyses. Both tumors exhibited characteristic genetic changes. One tumor was hypodiploid due to loss of entire chromosome 11; losses of 16p, 16q, 17p, chromosome 19 material, and loss of 22q12-qter. The other tumor was hyperdiploid and triploid, and displayed gain of 1q12-q23 and chromosome 9 material. Moreover, two morphological and genetically distinct cell lines have been established from both tumors, demonstrating underrepresentation of chromosomes 13, 14, 16, and 19. Karyotype descriptions of 120 WT with known clinical data together with data of this report confirm: (1) inter- and intratumor heterogeneity exists; (2) loss or underrepresentation of chromosome material at 11, 13, 14, 16, 17p, 19, and 22q in various combinations presents a new marker profile of resistance to cytotoxic agents regardless of the histological types; and (3) the prognostic impact of gain at 1q12-q23 sequences warrants further validation.

  1. Pulsed laser radiation therapy of skin tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kozlov, A.P.; Moskalik, K.G.

    1980-11-15

    Radiation from a neodymium laser was used to treat 846 patients with 687 precancerous lesions or benign tumors of the skin, 516 cutaneous carcinomas, 33 recurrences of cancer, 51 melanomas, and 508 metastatic melanomas in the skin. The patients have been followed for three months to 6.5 years. No relapses have been observed during this period. Metastases to regional lymph nodes were found in five patients with skin melanoma. Pulsed laser radiation may be successfully used in the treatment of precancerous lesions and benign tumors as well as for skin carcinoma and its recurrences, and for skin melanoma. Laser radiation is more effective in the treatment of tumors inaccessible to radiation therapy and better in those cases in which surgery may have a bad cosmetic or even mutilating effect. Laser beams can be employed in conjunction with chemo- or immunotherapy.

  2. Considering the role of radiation therapy for gastrointestinal stromal tumor

    Directory of Open Access Journals (Sweden)

    Corbin KS

    2014-05-01

    Full Text Available Kimberly S Corbin,1 Hedy L Kindler,2 Stanley L Liauw31Department of Radiation Oncology, Memorial Medical Center, Springfield, IL, USA; 2Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA; 3Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USAAbstract: Gastrointestinal stromal tumors (GISTs are rare mesenchymal tumors arising in the gastrointestinal tract. Over the last decade, the management and prognosis of GISTs has changed dramatically with molecular characterization of the c-kit mutation and the adoption of targeted systemic therapy. Currently, the standard of care for resectable tumors is surgery, followed by adjuvant imatinib for tumors at high risk for recurrence. Inoperable or metastatic tumors are treated primarily with imatinib. Despite excellent initial response rates, resistance to targeted therapy has emerged as a common clinical problem, with relatively few therapeutic solutions. While the treatment of GISTs does not commonly include radiotherapy, radiation therapy could be a valuable contributing modality. Several case reports indicate that radiation can control locally progressive, drug-resistant disease. Further study is necessary to define whether radiation could potentially prevent or delay the onset of drug resistance, or improve outcomes when given in combination with imatinib.Keywords: GIST, imatinib, radiotherapy

  3. Feasibility of boron neutron capture therapy for malignant spinal tumors

    International Nuclear Information System (INIS)

    Nakai, Kei; Kumada, Hiroaki; Yamamoto, Tetsuya; Tsurubuchi, Takao; Zaboronok, Alexander; Matsumura, Akira

    2009-01-01

    Treatment of malignant spinal cord tumors is currently ineffective. The characteristics of the spine are its seriality, small volume, and vulnerability: severe QOL impairment can be brought about by small neuronal damage. The present study aimed to investigate the feasibility of BNCT as a tumor-selective charged particle therapy for spinal cord tumors from the viewpoint of protecting the normal spine. A previous report suggested the tolerance dose of the spinal cord was 13.8 Gy-Eq for radiation myelopathy; a dose as high as 11 Gy-Eq demonstrated no spinal cord damage in an experimental animal model. We calculated the tumor dose and the normal spinal cord dose on a virtual model of a spinal cord tumor patient with a JAEA computational dosimetry system (JCDS) treatment planning system. The present study made use of boronophenylalanine (BPA). In these calculations, conditions were set as follows: tumor/normal (T/N) ratio of 3.5, blood boron concentration of 12 ppm, tumor boron concentration of 42 ppm, and relative biological effectiveness (RBE) values for tumor and normal spinal cord of 3.8 and 1.35, respectively. We examined how to optimize neutron irradiation by changing the beam direction and number. In our theoretical example, simple opposed two-field irradiation achieved 28.0 Gy-Eq as a minimum tumor dose and 7.3 Gy-Eq as a maximum normal spinal dose. The BNCT for the spinal cord tumor was therefore feasible when a sufficient T/N ratio could be achieved. The use of F-BPA PET imaging for spinal tumor patients is supported by this study.

  4. Photodynamic Therapy for Malignant Brain Tumors.

    Science.gov (United States)

    Akimoto, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area.

  5. Experimental tumor therapy - annual report 1982

    International Nuclear Information System (INIS)

    1983-08-01

    The present annual report is the fifth in a regular series and documents the continuity of the investigations in the field of experimental tumor therapy. The main points of emphasis of the activities relate above all to problems of dose fractionation and combination treatment. But if the present volume is compared with the previous ones the reader may be struck by the wider range of model systems used, especially of the tumors and normal tissues in which chronic radiation effects are investigated, and also by a concentration on those investigations that are important for solving clinical problems and that make use of many small fractions. Moreover, experiments were carried through in 1982 on the neutron beam set up at the Garching research reactor in order to characterise its biologic effect, which was a preparative measure in view of the planned clinical use. (orig./MG) [de

  6. Testicular tumors - clinical aspects and therapy

    International Nuclear Information System (INIS)

    Hirschmann, K.E.

    1981-01-01

    In this study the author reports about classification, clinical experience, therapy and therapeutic results of testicular tumors on the basis of results given in literature and of own investigations performed at the Clinic and Policlinic for Radiotherapy at Wuerzburg. In total, 97 patients with testicular tumors were examined and their cases analysed. These patients had received radiotherapy between January 1, 1962 and December 31, 1979. The difficulties with the intended classification of testicular tumors and the advantages and disadvantages of the individual nomenclatures are described. Consideration of the affected age-groups showed that this disease concerns mainly younger males with a high life expectancy. The study depicts the relatively discrete symptoms and signs and the difficulties connected with clinical diagnosis. A more generous indication for the exposition of the testicles is demanded. Also the lymphatic drainage of the testicular region, the resulting paths of metastatic spread and the difficulties connected with the lymphographic detection of metastases are described. There are three therapeutic measures: surgical intervention, radiotherapy and cytostatic treatment. With seminomas mandatory semitestectomy and radiotherapy will suffice; with other affections than seminomas, semitestectomy shall be followed by a combined therapy comprising removal of lymphatic nodes and cytostatic treatment and not so much radiotherapy. The results of treatment given in literature are compared with the own results. This comparison revealed good success with treatment of seminomas. With non-seminomal affections exclusive radiotherapy appears to be insufficient. Therefore a combined therapy is postulated, which must be rendered possible by a good interdisciplinary cooperation of pathologists, urologists and radiologists. (orig.) [de

  7. Complications of bone tumors after multimodal therapy

    Energy Technology Data Exchange (ETDEWEB)

    Shapeero, L.G., E-mail: lshapeero@usuhs.edu [Department of Radiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Bone and Soft Tissue Program, United States Military Cancer Institute, 6900 Georgia Ave, NW, Washington, DC 20307 (United States); Poffyn, B. [Department of Orthopaedic Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); De Visschere, P.J.L. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Sys, G. [Department of Orthopaedic Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Uyttendaele, D. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Vanel, D. [Department of Radiology, Rizzoli Institute, 40136 Bologna (Italy); Forsyth, R. [Department of Pathology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium); Verstraete, K.L. [Department of Radiology and Magnetic Resonance/MR-1K12 IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent (Belgium)

    2011-01-15

    Purpose: To define and compare the complications of bone tumors after resection, extracorporeal irradiation and re-implantation, with or without radiotherapy. Materials and methods: Eighty patients (40 males and 40 females, ages 4-77 years) with 61 malignant and 19 benign bone tumors were evaluated for local and distant complications after treatment. Two groups of patients were studied: (1) 53 patients had resection without (43 patients) or with external beam radiotherapy (RadRx) (10 patients) and (2) 27 patients underwent extracorporeal irradiation and re-implantation without (22 patients) or with RadRx (5 patients). Patient follow-up varied from 1 month to 13.63 years with mean follow-up of 4.7 years. Imaging studies included bone and chest radiography, spin echo T1- and T2-weighted (or STIR) magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), computed tomography (CT) for thoracic and abdominopelvic metastases and 3-phase technetium-99m-labeled-methylene-diphosphonate (Tc99m MDP) scintigraphy for bone metastases. Results: DCE-MRI differentiated the rapidly enhancing recurrences, residual tumors and metastases from the slowly enhancing inflammation, and the non-enhancing seromas and fibrosis. Recurrences, metastases (mainly to lung and bone), and seromas were greater than twice as frequent in patients after resection than after ECCRI. Although 11.3% of post-resection patients had residual tumor, no ECRRI-treated patient had residual tumor. In contrast, after ECRRI, infection was almost three times as frequent and aseptic loosening twice as frequent as compared with the post-resection patients. Bones treated with RadRx and/or ECRRI showed increased prevalence of fractures and osteoporosis. In addition, muscle inflammation was more common in the externally irradiated patient as compared with the patient who did not receive this therapy. However, another soft tissue complication, heterotopic ossification, was rare in the

  8. Radiation therapy for malignant lid tumor

    International Nuclear Information System (INIS)

    Totsuka, Seiichi; Itsuno, Hajime

    1991-01-01

    The case of a 42-year-old man with Meibomian gland carcinoma in his right lower lid is reported. The tumor found in the nasal part of the lower lid, was 12 mm x 13 mm in size. First, surgical resection was performed. The pathological diagnosis of the frozen section was 'undifferentiated basal cell epithelioma'. Second, cryotherapy was performed all over the cut surface. Later, the permanent section was pathologically diagnosed as 'undifferentiated Meibomian gland carcinoma'. Total 50 Gy irradiation therapy was therefore performed using a 9 Mev Linac electron beam, 25 x 20 mm field, with a lead protector for the cornea and lens. A lead contact lens did not afford good results because it was too easily shifted on the cornea, owing to its weight. Therefore, we made a racket-shaped lead protector. Fixed well with tape, this protector afforded good protective effect. Three years after treatment, the patient has good visual function, with no recurrence. This racket-shaped lead protector is thought to be useful in radiation therapy for malignant lid tumors. (author)

  9. Tumor Volume Changes on 1.5 Tesla Endorectal MRI During Neoadjuvant Androgen Suppression Therapy for Higher-Risk Prostate Cancer and Recurrence in Men Treated Using Radiation Therapy Results of the Phase II CALGB 9682 Study

    International Nuclear Information System (INIS)

    D'Amico, Anthony V.; Halabi, Susan; Tempany, Clare; Titelbaum, David; Philips, George K.; Loffredo, Marian; McMahon, Elizabeth; Sanford, Ben; Vogelzang, Nicholas J.; Small, Eric J.

    2008-01-01

    Purpose: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. Patients and Methods: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). Results: After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. Conclusion: Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST

  10. 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

  11. TU-G-BRA-05: Predicting Volume Change of the Tumor and Critical Structures Throughout Radiation Therapy by CT-CBCT Registration with Local Intensity Correction

    Energy Technology Data Exchange (ETDEWEB)

    Park, S; Robinson, A; Kiess, A; Quon, H; Wong, J; Lee, J [Johns Hopkins University, Baltimore, MD (United States); Plishker, W [IGI Technologies Inc., College Park, MD (United States); Shekhar, R [IGI Technologies Inc., College Park, MD (United States); Children’s National Medical Center, Washington, D.C. (United States)

    2015-06-15

    Purpose: The purpose of this study is to develop an accurate and effective technique to predict and monitor volume changes of the tumor and organs at risk (OARs) from daily cone-beam CTs (CBCTs). Methods: While CBCT is typically used to minimize the patient setup error, its poor image quality impedes accurate monitoring of daily anatomical changes in radiotherapy. Reconstruction artifacts in CBCT often cause undesirable errors in registration-based contour propagation from the planning CT, a conventional way to estimate anatomical changes. To improve the registration and segmentation accuracy, we developed a new deformable image registration (DIR) that iteratively corrects CBCT intensities using slice-based histogram matching during the registration process. Three popular DIR algorithms (hierarchical B-spline, demons, optical flow) augmented by the intensity correction were implemented on a graphics processing unit for efficient computation, and their performances were evaluated on six head and neck (HN) cancer cases. Four trained scientists manually contoured nodal gross tumor volume (GTV) on the planning CT and every other fraction CBCTs for each case, to which the propagated GTV contours by DIR were compared. The performance was also compared with commercial software, VelocityAI (Varian Medical Systems Inc.). Results: Manual contouring showed significant variations, [-76, +141]% from the mean of all four sets of contours. The volume differences (mean±std in cc) between the average manual segmentation and four automatic segmentations are 3.70±2.30(B-spline), 1.25±1.78(demons), 0.93±1.14(optical flow), and 4.39±3.86 (VelocityAI). In comparison to the average volume of the manual segmentations, the proposed approach significantly reduced the estimation error by 9%(B-spline), 38%(demons), and 51%(optical flow) over the conventional mutual information based method (VelocityAI). Conclusion: The proposed CT-CBCT registration with local CBCT intensity correction

  12. Recent Progress in the Medical Therapy of Pituitary Tumors

    Directory of Open Access Journals (Sweden)

    Fabienne Langlois

    2017-05-01

    Full Text Available Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD. In the case of non-functioning pituitary adenomas (NFAs, pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.

  13. 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

  14. Epigenetic changes in solid and hematopoietic tumors.

    Science.gov (United States)

    Toyota, Minoru; Issa, Jean-Pierre J

    2005-10-01

    There are three connected molecular mechanisms of epigenetic cellular memory in mammalian cells: DNA methylation, histone modifications, and RNA interference. The first two have now been firmly linked to neoplastic transformation. Hypermethylation of CpG-rich promoters triggers local histone code modifications resulting in a cellular camouflage mechanism that sequesters gene promoters away from transcription factors and results in stable silencing. This normally restricted mechanism is ubiquitously used in cancer to silence hundreds of genes, among which some critically contribute to the neoplastic phenotype. Virtually every pathway important to cancer formation is affected by this process. Methylation profiling of human cancers reveals tissue-specific epigenetic signatures, as well as tumor-specific signatures, reflecting in particular the presence of epigenetic instability in a subset of cancers affected by the CpG island methylator phenotype. Generally, methylation patterns can be traced to a tissue-specific, proliferation-dependent accumulation of aberrant promoter methylation in aging tissues, a process that can be accelerated by chronic inflammation and less well-defined mechanisms including, possibly, diet and genetic predisposition. The epigenetic machinery can also be altered in cancer by specific lesions in epigenetic effector genes, or by aberrant recruitment of these genes by mutant transcription factors and coactivators. Epigenetic patterns are proving clinically useful in human oncology via risk assessment, early detection, and prognostic classification. Pharmacologic manipulation of these patterns-epigenetic therapy-is also poised to change the way we treat cancer in the clinic.

  15. 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

  16. Adenomatoid odontogenic tumor with clear cell changes

    Directory of Open Access Journals (Sweden)

    Neeta Mohanty

    2014-01-01

    Full Text Available Adenomatoid odontogenic tumor (AOT has a limited biological profile and been an attention-grabbing tumor for a century for its origin. Though described earlier, it was widely accepted after Harbitz from Norway reported about this uncommon benign tumor in 1915. There has been a long debate as whether this tumor is a hamartoma or a neoplasm. Here, we present a case of AOT in a 20-year-old female with details of clinical, radiological and histological features along with clear cell changes, signifying AOT to be more aggressive in nature than assessed from earlier literature. Thus, we did an extensive search of PubMed literature on AOT with all its histopathological features associated until date to find the report of clear cell changes yet.

  17. [Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

    Science.gov (United States)

    Fischer, H-P

    2005-05-01

    High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases

  18. Current applications and future prospects of nanomaterials in tumor therapy

    Directory of Open Access Journals (Sweden)

    Huang Y

    2017-03-01

    Full Text Available Yu Huang,1 Chao-Qiang Fan,1 Hui Dong,1 Su-Min Wang,1 Xiao-Chao Yang,2 Shi-Ming Yang1 1Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China; 2Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Tumors are one of the most serious human diseases and cause numerous global deaths per year. In spite of many strategies applied in tumor therapy, such as radiation therapy, chemotherapy, surgery, and a combination of these treatments, tumors are still the foremost killer worldwide among human diseases, due to their specific limitations, such as multidrug resistance and side effects. Therefore, it is urgent and necessary to develop new strategies for tumor therapy. Recently, the fast development of nanoscience has paved the way for designing new strategies to treat tumors. Nanomaterials have shown great potential in tumor therapy, due to their unique properties, including passive targeting, hyperthermia effects, and tumor-specific inhibition. This review summarizes the recent progress using the innate antitumor properties of metallic and nonmetallic nanomaterials to treat tumors, and related challenges and prospects are discussed. Keywords: tumor, nanomaterials, nanoparticles, nanotechnology

  19. 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.

  20. 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

  1. mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

    International Nuclear Information System (INIS)

    Fotin-Mleczek, Mariola; Zanzinger, Kai; Heidenreich, Regina; Lorenz, Christina; Kowalczyk, Aleksandra; Kallen, Karl-Josef; Huber, Stephan M

    2014-01-01

    The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4 + , CD8 + and NKT cell infiltration of mouse tumors. Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. The online version of this article (doi:10.1186/1748-717X-9-180) contains supplementary material, which is available to authorized users

  2. Selected anti-tumor vaccines merit a place in multimodal tumor therapies

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, Eva-Maria; Wunderlich, Roland [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Ebel, Nina [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Rubner, Yvonne [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Schlücker, Eberhard [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Meyer-Pittroff, Roland [Competence Pool Weihenstephan, Technische Universität München, Freising (Germany); Ott, Oliver J.; Fietkau, Rainer; Gaipl, Udo S.; Frey, Benjamin, E-mail: benjamin.frey@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany)

    2012-10-09

    Multimodal approaches are nowadays successfully applied in cancer therapy. Primary locally acting therapies such as radiotherapy (RT) and surgery are combined with systemic administration of chemotherapeutics. Nevertheless, the therapy of cancer is still a big challenge in medicine. The treatments often fail to induce long-lasting anti-tumor responses. Tumor recurrences and metastases result. Immunotherapies are therefore ideal adjuncts to standard tumor therapies since they aim to activate the patient's immune system against malignant cells even outside the primary treatment areas (abscopal effects). Especially cancer vaccines may have the potential both to train the immune system against cancer cells and to generate an immunological memory, resulting in long-lasting anti-tumor effects. However, despite promising results in phase I and II studies, most of the concepts finally failed. There are some critical aspects in development and application of cancer vaccines that may decide on their efficiency. The time point and frequency of medication, usage of an adequate immune adjuvant, the vaccine's immunogenic potential, and the tumor burden of the patient are crucial. Whole tumor cell vaccines have advantages compared to peptide-based ones since a variety of tumor antigens (TAs) are present. The master requirements of cell-based, therapeutic tumor vaccines are the complete inactivation of the tumor cells and the increase of their immunogenicity. Since the latter is highly connected with the cell death modality, the inactivation procedure of the tumor cell material may significantly influence the vaccine's efficiency. We therefore also introduce high hydrostatic pressure (HHP) as an innovative inactivation technology for tumor cell-based vaccines and outline that HHP efficiently inactivates tumor cells by enhancing their immunogenicity. Finally studies are presented proving that anti-tumor immune responses can be triggered by combining RT with selected

  3. Navigating cancer network attractors for tumor-specific therapy

    DEFF Research Database (Denmark)

    Creixell, Pau; Schoof, Erwin; Erler, Janine Terra

    2012-01-01

    understanding of the processes by which genetic lesions perturb these networks and lead to disease phenotypes. Network biology will help circumvent fundamental obstacles in cancer treatment, such as drug resistance and metastasis, empowering personalized and tumor-specific cancer therapies....

  4. Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship.

    Science.gov (United States)

    Netea-Maier, Romana T; Smit, Johannes W A; Netea, Mihai G

    2018-01-28

    In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs). In response to cues present in the TME, among which products of altered tumor cell metabolism, TAMs are also required to reprogram their metabolism, with activation of glycolysis, fatty acid synthesis and altered nitrogen cycle metabolism. These changes result in functional reprogramming of TAMs which includes changes in the production of cytokines and angiogenetic factors, and contribute to the tumor progression and metastasis. Understanding the metabolic changes governing the intricate relationship between the tumor cells and the TAMs represents an essential step towards developing novel therapeutic approaches targeting the metabolic reprogramming of the immune cells to potentiate their tumoricidal potential and to circumvent therapy resistance. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Skeletal sequelae of radiation therapy for malignant childhood tumors

    International Nuclear Information System (INIS)

    Butler, M.S.; Robertson, W.W. Jr.; Rate, W.; D'Angio, G.J.; Drummond, D.S.

    1990-01-01

    One hundred forty-three patients who received radiation therapy for childhood tumors, and survived to the age of skeletal maturity, were studied by retrospective review of oncology records and roentgenograms. Diagnoses for the patients were the following: Hodgkin's lymphoma (44), Wilms's tumor (30), acute lymphocytic leukemia (26), non-Hodgkin's lymphoma (18), Ewing's sarcoma (nine), rhabdomyosarcoma (six), neuroblastoma (six), and others (four). Age at the follow-up examination averaged 18 years (range, 14-28 years). Average length of follow-up study was 9.9 years (range, two to 18 years). Asymmetry of the chest and ribs was seen in 51 (36%) of these children. Fifty (35%) had scoliosis; 14 had kyphosis. In two children, the scoliosis was treated with a brace, while one developed significant kyphosing scoliosis after laminectomy and had spinal fusion. Twenty-three (16%) patients complained of significant pain at the radiation sites. Twelve of the patients developed leg-length inequality; eight of those were symptomatic. Three patients developed second primary tumors. Currently, the incidence of significant skeletal sequelae is lower and the manifestations are less severe than reported in the years from 1940 to 1970. The reduction in skeletal complications may be attributed to shielding of growth centers, symmetric field selection, decreased total radiation doses, and sequence changes in chemotherapy

  6. Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

    Directory of Open Access Journals (Sweden)

    Christian Bressy

    2017-06-01

    Full Text Available Oncolytic virus (OV therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53 or another p53 family member (TP63 or TP73 were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

  7. Radiation therapy for primary spinal cord tumors in adults

    International Nuclear Information System (INIS)

    Jeremic, B.; Grujicic, D.; Jovanovic, D.; Djuric, L.; Mijatovic, L.

    1990-01-01

    This paper evaluates the role of radiation therapy in management of primary spinal cord tumors in adults. Records of 21 patients with primary spinal cord tumors treated with radiation therapy after surgery were retrospectively reviewed. Histologic examination showed two diffuse and 10 localized ependymomas, six low-grade gliomas, and three malignant gliomas. Surgery consisted of gross tumor resection in six patients, subtotal resection in three patients, and biopsy in 12 patients. Three patients also received chemotherapy. Radiation dose range from 45 to 55 Cy

  8. Skeletal changes in growing spine following radiotherapy of tumors

    International Nuclear Information System (INIS)

    Spissak, L.; Horniakova, M.

    1987-01-01

    An analysis is given of a group of 20 children after nephrectomy and radiotherapy of Wilms' tumor and of one child following ovariectomy and radiotherapy of a dysgermanoma more than 5 years after the termination of the therapy. Morphological and structural changes were evaluated in the vertebrae as well as axial alterations of the spine. Interrelationships were found between the radiation dose, the patient's age and the degree of the skeletal changes in the spine. The most pronounced morphological, structural and axial changes occurred in children below 4 years treated with radiation doses above 20.0 Gy. (author). 1 tab., 5 figs., 3 refs

  9. Nanobody-based cancer therapy of solid tumors

    NARCIS (Netherlands)

    Kijanka, Marta|info:eu-repo/dai/nl/328212792; Dorresteijn, Bram|info:eu-repo/dai/nl/31401635X; Oliveira, Sabrina; van Bergen en Henegouwen, Paul M P|info:eu-repo/dai/nl/071919481

    The development of tumor-targeted therapies using monoclonal antibodies has been successful during the last 30 years. Nevertheless, the efficacy of antibody-based therapy is still limited and further improvements are eagerly awaited. One of the promising novel developments that may overcome the

  10. Therapy with radiolabelled somatostatin analogs in neuroendocrine tumors

    International Nuclear Information System (INIS)

    Kunikowska, J.; Krolicki, L.

    2007-01-01

    In the 80's the discovery of somatostatin receptors expression on NET cells enabled the application of somatostatin analogues in diagnosis and therapy. Initially, 'cold' somatostatin analogs were used for therapeutical purpose, with overall good clinical response, but with minimal anti-proliferation effect. Furthermore, radiolabelled receptor-binding peptides have been shown to be an important class of radiopharmaceuticals for tumor diagnosis and therapy with minimal side-effects. Specific binding between receptor on tumor cell and peptide with beta emitting radionuclide act not only on tumor related symptoms but also on tumor cell via radiotoxic effect of beta radiation. Discoveries of next receptor combinations, allow the work over synthesis and applications of next receptors' analogs both in diagnosis and in therapy. Due to complex characteristics of NET's, the use therapeutic 'cocktail' containing the variety analogs may be of great importance. (author)

  11. Theranostic GO-based nanohybrid for tumor induced imaging and potential combinational tumor therapy.

    Science.gov (United States)

    Qin, Si-Yong; Feng, Jun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Liu, Xiang-Ji; Luo, Guo-Feng; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-02-12

    Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors

    DEFF Research Database (Denmark)

    Persson, Bertil R R; Koch, Catrin Bauréus; Grafström, Gustav

    2010-01-01

    Single-fraction radiation therapy with 5 or 15 Gy (60)Co gamma radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-gamma)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumor...

  13. Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy

    Czech Academy of Sciences Publication Activity Database

    Aaltonen, K. E.; Novosadová, Vendula; Bendahl, P.-O.; Graffman, C.; Larsson, A.-M.; Ryden, L.

    2017-01-01

    Roč. 8, č. 28 (2017), s. 45544-45565 ISSN 1949-2553 Institutional support: RVO:86652036 Keywords : metastatic breast cancer * circulating tumor cells * gene expression Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 5.168, year: 2016

  14. Intensity-Modulated Radiation Therapy for Primary Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhong-min Wang

    2004-01-01

    Radiation therapy has been used to treat primary brain tumors as standard primary and/or adjunctive therapies for decades. It is difficult for conventional radiotherapy to deliver a lethal dose of radiation to the tumors while sparing surrounding normal brain due to complicated structures and multifunction in human brain. With the understanding of radiation physics and computer technology, a number of novel and more precise radiotherapies have been developed in recent years. Intensity modulated radiotherapy (IMRT) is one of these strategies. The use of IMRT in the treatment of primary brain tumors is being increasing nowadays. It shows great promise for some of primary brain tumors and also presents some problems, This review highlights current IMRT in the treatment of mainly primary brain tumors.

  15. Obstacles to Brain Tumor Therapy: Key ABC Transporters

    Directory of Open Access Journals (Sweden)

    Juwina Wijaya

    2017-11-01

    Full Text Available The delivery of cancer chemotherapy to treat brain tumors remains a challenge, in part, because of the inherent biological barrier, the blood–brain barrier. While its presence and role as a protector of the normal brain parenchyma has been acknowledged for decades, it is only recently that the important transporter components, expressed in the tightly knit capillary endothelial cells, have been deciphered. These transporters are ATP-binding cassette (ABC transporters and, so far, the major clinically important ones that functionally contribute to the blood–brain barrier are ABCG2 and ABCB1. A further limitation to cancer therapy of brain tumors or brain metastases is the blood–tumor barrier, where tumors erect a barrier of transporters that further impede drug entry. The expression and regulation of these two transporters at these barriers, as well as tumor derived alteration in expression and/or mutation, are likely obstacles to effective therapy.

  16. MR imaging assisted radiation therapy planning of brain tumors

    International Nuclear Information System (INIS)

    Just, M.; Roesler, H.P.; Higer, H.P.; Kutzner, J.; Thelen, M.

    1990-01-01

    This paper reports on the improvement of the accuracy of treatment portals in radiation therapy of brain tumors with use of MR imaging. After proper processing, the parasagittal MR image showing the largest tumor size and the midline sagittal image were superimposed. With common anatomic landmarks of midline tomogram and lateral simulation radiograph, commensurate reference grids were laid over both images in identical positions. Tumor coordinates were then transferred from the synthesized MR image to the lateral radiograph. Rectangular fields or individual shielding blocks encompassing the tumor could be drawn directly. This new method was used in 17 patients, and results were compared with CT-assisted results

  17. Bone changes from prostaglandin therapy

    International Nuclear Information System (INIS)

    Poznanski, A.K.; Fernbach, S.K.; Berry, T.E.; Northwestern Univ., Chicago, IL

    1985-01-01

    Prostaglandin E therapy in infants causes periosteal elevation. Although the changes usually take 30-40 days to become visible, we have seen them as early as nine days. In 15 infants who had prostaglandin E therapy for over six days, three developed periosteal elevation. Three other cases are described in greater detail, with long-term follow-up in two in which the bone remodeled to normal. Gallium scan in one showed increased uptake in areas involved. The periosteal cloaking may mimic Caffey disease but the pattern of involvement is different, since the mandible, which is commonly affected in Caffey disease, is rarely involved in prostaglandin E therapy. (orig.)

  18. Contributions of nuclear medicine to the therapy of malignant tumors

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E. (Forschungszentrum Juelich GmbH (Germany). Inst. fuer Medizin Duesseldorf Univ. (Germany). Nuklearmedizinische Klinik)

    1991-11-01

    The diagnostic and therapeutic application of radionuclides on oncology has led to an increased efficiency in the treatment of malignant tumors. - Regarding diagnosis, measuring metabolic reactions in tumor tissue, especially by positron emission tomography, opened the potential for assaying tumor response to different treatment modalities and thus eventually for tailoring effective treatment of a given tumor in the individual patient. - Regarding treatment, attention is given to the choice of the radionuclide for optimal deposition of the desired radiation in tumor cells avoiding exposure of normal cells; in this context microdosimetric considerations are essential with respect to {beta}-emitters, {alpha}-emitters, the Auger-effect and neutron capture therapy. Examples of therapeutic uses of radionuclides in the inorganic form are 131-I for thyroid cancer and 32-P for polycythemia vera; organically bound radionuclides are employed with precursors for tumor cell metabolism or with receptor seeking agents, such as MIBG and monoclonal antibodies which presently enjoy a particular interest and bear great promise. Stable nuclides, if property accumulated within tumors, may be activated for therapy in situ, for example by thermal neutrons, as in neutron capture therapy using the 10-B (n, {alpha})7-Li reaction. - Treatment planning and execution with radionuclides have gained momentum over the past decade, yet much more needs to be done. (orig.).

  19. Photodynamic therapy-generated vaccines prevent tumor recurrence after radiotherapy

    International Nuclear Information System (INIS)

    Korbelik, M.; Sun, J.

    2003-01-01

    Photodynamic therapy (PDT), an established clinical modality for a variety of malignant and non-malignant diseases, inflicts photoreactive drug-mediated oxidative stress that prompts the engagement of host inflammatory and immune responses which contribute to the therapy outcome. Recently, it has become evident that in vitro PDT-treated tumor cells or their lysates can be utilized as an effective vaccine against established tumors of the same origin. The mechanism underlying the vaccine action appears to be based on eliciting immune recognition of the tumor and developing an efficient immune response even against poorly immunogenic tumors. This study examined whether PDT-generated vaccines can be effectively combined with radiotherapy. Subcutaneous SCCVII tumors (squamous cell carcinomas) growing in syngeneic C3H/HeN mice were treated by radiotherapy (60 Gy x-ray dose). PDT-vaccine treatment, done by peritumoral injection of in vitro PDT-treated SCCVII cells (20 million/mouse), was performed either immediately after radiotherapy or ten days later. The mice were then observed for tumor regression/recurrence. The tumors treated with radiotherapy alone shrunk and became impalpable for a brief period after which they all recurred. In contrast, vaccination performed at 10 days post radiotherapy delayed tumor recurrence and prevented it in one of six mice. Even better results were obtained with mice vaccinated immediately after radiotherapy, with mice showing not only a delayed tumor recurrence but also no sign of tumor in 50% of mice. The PDT-vaccine treatment without radiotherapy produced in this trial a significant tumor growth retardation but no complete regressions. These results indicate that PDT-generated vaccines can ensure immune rejection of cancer once the lesion size is reduced by radiotherapy. Even without obtaining a systemic immunity for the elimination of disseminated malignant deposits, these findings suggest that PDT-vaccines can improve local control

  20. Technological progress in radiation therapy for brain tumors

    LENUS (Irish Health Repository)

    Vernimmen, Frederik Jozef

    2014-01-01

    To achieve a good therapeutic ratio the radiation dose to the tumor should be as high as possible with the lowest possible dose to the surrounding normal tissue. This is especially the case for brain tumors. Technological ad- vancements in diagnostic imaging, dose calculations, and radiation delivery systems, combined with a better un- derstanding of the pathophysiology of brain tumors have led to improvements in the therapeutic results. The widely used technology of delivering 3-D conformal therapy with photon beams (gamma rays) produced by Li-near Accelerators has progressed into the use of Intensity modulated radiation therapy (IMRT). Particle beams have been used for several decades for radiotherapy because of their favorable depth dose characteristics. The introduction of clinically dedicated proton beam therapy facilities has improved the access for cancer patients to this treatment. Proton therapy is of particular interest for pediatric malignancies. These technical improvements are further enhanced by the evolution in tumor physiology imaging which allows for improved delineation of the tumor. This in turn opens the potential to adjust the radiation dose to maximize the radiobiological effects. The advances in both imaging and radiation therapy delivery will be discussed.

  1. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    Science.gov (United States)

    Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

    2011-01-01

    Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention. PMID:22162712

  2. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    Directory of Open Access Journals (Sweden)

    Marc Baay

    2011-01-01

    Full Text Available Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs, which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention.

  3. Family therapy, conflicts and change

    DEFF Research Database (Denmark)

    Musaeus, Peter

    2007-01-01

    Given the relative lack of sociocultural approaches to therapy, this presentation aims to contribute to a sociocultural understanding of motivation and socio-emotional problems in children and families undergoing family therapy. The study was designed as a case study using semi structured...... will be sketched pertaining to the area of family therapy. The study argues for the importance of a holistic, non-mechanical (Valsiner) approach to motivation for change in understanding how "at risk" or "problematic" children and youth (who are for instance experiencing school absenteeism, domestic violence...... interviews with 15 families undergoing family therapy delivered by a communal agency in Denmark.   Using notions of crisis interlinked with institutions and everyday lives (Hedegaard) framed by historical, contentious struggles (Holland and Lave), a model of conflict, violence, learning and motivation...

  4. Boron neutron capture therapy for children with malignant brain tumor

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Komatsu, Hisao; Kageji, Teruyoshi; Tsuji, Fumio; Matsumoto, Keizo; Kitamura, Katsuji; Hatanaka, Hiroshi; Minobe, Takashi.

    1993-01-01

    Among the 131 cases with brain tumors treated by boron-neutron capture therapy (BNCT), seventeen were children. Eight supratentorial tumors included five astrocytomas(grade 2-4), two primitive neuroectodermal tumors (PNET) and one rhabdomyosarcoma. Seven pontine tumors included one astrocytoma, one PNET and 5 unverified gliomas. Two cerebellar tumors (PNET and astrocytoma) were also treated. All pontine tumors showed remarkable decrease in size after BNCT. However, most of them showed regrowth of the tumors because the neutrons were insufficient due to the depth. Four cases with cerebral tumor died of remote cell dissemination, although they all responded to BNCT. One of them survived 7 years after repeated BNCTs. An 11 years old girl with a large astrocytoma in the right frontal lobe has lived more than 11 years and is now a draftswoman at a civil engineering company after graduating from a technical college. An 8 years old girl with an astrocytoma in the left occipital lobe has no recurrence of the tumor for 2 years and attends on elementary school without mental and physical problems. Two children (one year old girl and four years old boy) with cerebellar tumors have shown showed an excellent growth after BNCT and had no neurological deficits. Mental and physical development in patients treated by BNCT is usually better than that in patients treated by conventional radiotherapy. (author)

  5. [Effectiveness of heart tumor therapy in the cardiology department during 7 year follow-up].

    Science.gov (United States)

    Dabek, Józefa; Twardowski, Romuald; Jakubowski, Daniel; Michniak, Barbara; Swiderski, Robert; Gasior, Zbigniew

    2009-11-01

    Neoplasms of the heart are rare. Usually asymptomatic on the early stage are diagnosed incidentally. Among primary heart neoplasms the most often benign tumors are diagnosed--mostly myxomas, whereas the majority of malignant heart tumors are sarcomas. The aim of this paper was to present heart tumors diagnosed in the cardiology department, their symptoms, used diagnostic tests and therapy and to show after therapy quality of life changes. There were 18 patients included to the study, whom during hospitalization in the cardiology department heart tumors were diagnosed. There were 11 women and 7 men, aged from 33- to 76-years-old (mean 60,5 years). To all of the patients medical interview, physical examination, EKG, UCG and laboratory test were performed. Additionally in some cases computed tomography or magnetic resonance imaging of the chest and coronary angiograms were done. Based on the diagnostic tests results the patients were qualified to conservative or surgical treatment. Among 18 heart tumor patients in 12 cases primary benign tumors were diagnosed (66,6%), 1 patient had primary malignant tumor (5,5%), there were 3 cases of metastatic tumors (16,6%) and 2 patients with non-neoplasmic tumors--clots (11,1%). From 18 subjects with heart tumor 3 patients died because of advanced stage of neoplasmic disease and presence of metastatic tumors in the heart. Results of the study show, that heart tumors, regardless of development of diagnostic tests, are still diagnosed too late. The study group follow-up proved, that early diagnosis and proper heart tumor treatment prevented complications and improved the quality of life. It is worth to emphasize, that coronary angiogram in some cases allowed to diagnose coronary artery disease, to treat heart tumor and to perform coronary artery by-pass grafting simultaneously.

  6. Tumor exosomes: cellular postmen of cancer diagnosis and personalized therapy.

    Science.gov (United States)

    Sharma, Aman; Khatun, Zamila; Shiras, Anjali

    2016-02-01

    Nanosized (30-150 nm) extracellular vesicles 'exosomes' are secreted by cells for intercellular communication during normal and pathological conditions. Exosomes carry biomacromolecules from cell-of-origin and, therefore, represent molecular bioprint of the cell. Tumor-derived exosomes or TDEx modulate tumor microenvironment by transfer of macromolecules locally as well as at distant metastatic sites. Due to their biological stability, TDEx are rich source of biomarkers in cancer patients. TDEx focused cancer diagnosis allows liquid biopsy-based tumor typing and may facilitate therapy response monitoring by developing novel exosomes diagnostics. Therefore, efficient and specific capturing of exosomes for subsequent amplification of the biomessages; for example, DNA, RNA, miRNA can reinvent cancer diagnosis. Here, in this review, we discuss advancements in exosomes isolation strategies, presence of exosomes biomarkers and importance of TDEx in gauging tumor heterogeneity for their potential use in cancer diagnosis, therapy.

  7. Chemothermal Therapy for Localized Heating and Ablation of Tumor

    Directory of Open Access Journals (Sweden)

    Zhong-Shan Deng

    2013-01-01

    Full Text Available Chemothermal therapy is a new hyperthermia treatment on tumor using heat released from exothermic chemical reaction between the injected reactants and the diseased tissues. With the highly minimally invasive feature and localized heating performance, this method is expected to overcome the ubiquitous shortcomings encountered by many existing hyperthermia approaches in ablating irregular tumor. This review provides a relatively comprehensive review on the latest advancements and state of the art in chemothermal therapy. The basic principles and features of two typical chemothermal ablation strategies (acid-base neutralization-reaction-enabled thermal ablation and alkali-metal-enabled thermal/chemical ablation are illustrated. The prospects and possible challenges facing chemothermal ablation are analyzed. The chemothermal therapy is expected to open many clinical possibilities for precise tumor treatment in a minimally invasive way.

  8. Diagnosis and surgical therapy of pancreas tumors

    International Nuclear Information System (INIS)

    Heid, A.

    1981-01-01

    The efficiency of surgery and presurgical diagnosis on several tumorous diseases of the pancreas is investigated. If there is the clinical suspicion of a pancreas carcinoma, sonography computerized tomography, and endoscopic-retrograde cholangio-pancreaticography (ERCP) bring the best diagnostic results. In case of pancreatogenic hyperinsulinism a selective angiography should be carried out in any case for an exact presurgical localisation. (orig./MG) [de

  9. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    International Nuclear Information System (INIS)

    Hosseinkhani, Hossein; Chen Yiru; He Wenjie; Hong Poda; Yu, Dah-Shyong; Domb, Abraham J.

    2013-01-01

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe 2+ solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  10. Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinkhani, Hossein, E-mail: hosseinkhani@yahoo.com [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Chen Yiru [National Yang-Ming University, Department of Biomedical Engineering (China); He Wenjie; Hong Poda [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Yu, Dah-Shyong [Nanomedicine Research Center, National Defense Medical Center (China); Domb, Abraham J. [Institute of Drug Research, The Center for Nanoscience and Nanotechnology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem (Israel)

    2013-01-15

    This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe{sup 2+} solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

  11. Atypical Teratoid Rhabdoid Tumor: Current Therapy and Future Directions

    Energy Technology Data Exchange (ETDEWEB)

    Ginn, Kevin F.; Gajjar, Amar, E-mail: amar.gajjar@stjude.org [Division of Neuro-Oncology, St. Jude Children’s Research Hospital, Memphis, TN (United States)

    2012-09-12

    Atypical teratoid rhabdoid tumors (ATRTs) are rare central nervous system tumors that comprise approximately 1–2% of all pediatric brain tumors; however, in patients less than 3 years of age this tumor accounts for up to 20% of cases. ATRT is characterized by loss of the long arm of chromosome 22 which results in loss of the hSNF5/INI-1 gene. INI1, a member of the SWI/SNF chromatin remodeling complex, is important in maintenance of the mitotic spindle and cell cycle control. Overall survival in ATRT is poor with median survival around 17 months. Radiation is an effective component of therapy but is avoided in patients younger than 3 years of age due to long term neurocognitive sequelae. Most long term survivors undergo radiation therapy as a part of their upfront or salvage therapy, and there is a suggestion that sequencing the radiation earlier in therapy may improve outcome. There is no standard curative chemotherapeutic regimen, but anecdotal reports advocate the use of intensive therapy with alkylating agents, high-dose methotrexate, or therapy that includes high-dose chemotherapy with stem cell rescue. Due to the rarity of this tumor and the lack of randomized controlled trials it has been challenging to define optimal therapy and advance treatment. Recent laboratory investigations have identified aberrant function and/or regulation of cyclin D1, aurora kinase, and insulin-like growth factor pathways in ATRT. There has been significant interest in identifying and testing therapeutic agents that target these pathways.

  12. Malignant tumors arising in the maxillary region after radiation therapy

    International Nuclear Information System (INIS)

    Shimizu, Sawamichi; Shirahata, Yuichi; Uchida, Yutaka

    1984-01-01

    Although radiotherapy has proven of great therapeutic value in the treatment of malignant tumors, it should also be borne in mind that radiation has a serious potential risk of giving rise to a secondary malignancy. We recently experienced 2 cases each of carcinoma and sarcoma arising in the irradiated areas long after radiation therapy for malignant tumors. In these 4 cases, 2 males and 2 females, the primary neoplastic diseases were squamous cell carcinoma, epidermoid carcinoma, carcinoma of unknown pathology and malignant lymphoma, and the secondary tumors were epidermoid carcinoma, squamous cell carcinoma, osteosarcoma and chondrosarcoma, respectively. The sites of occurrence of these malignancies were invariably in the maxillary region; the mean latent period was 15 years, aside from an infantile case with a latent period of 5 years. In view of the primary diseases being malignant tumors the following criteria were set up for the diagnosis of radiation-induced malignancies: (1) the site of occurrence is within the confines of a previously irradiated area, (2) the latent period is prolonged and (3) the malignancy occurs as a double tumor. Therapy was primarily by operation. The prognosis was exceedingly ominous, the average survival time being 22 months. This was probably and mainly because of rapidity of tumor growth. Thus, the secondary tumors had already spread back to inward by the time they were first discovered. This should be kept in mind during a long-term follow-up of patients receiving radiotherapy for malignancy. (author)

  13. Possible role of reassortment in tumor therapy

    International Nuclear Information System (INIS)

    Terashima, Toyozo

    1976-01-01

    On the basis of age-dependent response pattern of cultured mammalian cells, various exogenous agents, such as x-ray, antimetabolites, and antitumor drugs, were classified into two groups, i.e., x-ray type (A) and hydroxyurea type (B). Each type of agent was specific not only for the pattern of survival response during the cell cycle but also for the inhibition of progression. The treatment of cycling cell population with either type of agent results in the reassortment of cells in relation to cell age, thereby providing a chance for successive administrations of either type of agent. Taking advantage of such specific effects of agents on the tumor cell cycle, possible schedules for efficient cell sterilization were suggested: B.X(simultaneous administration) and A-X, X-B(two successive administrations at a scheduled interval) were found promissing. Finally, it was emphasized that much more information must be collected to formulate the cellular response of cycling and non-cycling fractions of the tumor to various exogenous agents. (J.P.N.)

  14. Radiation therapy of 9L rat brain tumors

    International Nuclear Information System (INIS)

    Henderson, S.D.; Kimler, B.F.; Morantz, R.A.

    1981-01-01

    The effects of radiation therapy on normal rats and on rats burdened with 9L brain tumors have been studied. The heads of normal rats were x-irradiated with single exposures ranging from 1000 R to 2700 R. Following acute exposures greater than 2100 R, all animals died in 8 to 12 days. Approximately 30% of the animals survived beyond 12 days over the range of 1850 to 1950 R; following exposures less than 1850 R, all animals survived the acute radiation effects, and median survival times increased with decreasing exposure. Three fractionated radiation schedules were also studied: 2100 R or 3000 R in 10 equal fractions, and 3000 R in 6 equal fractions, each schedule being administered over a 2 week period. The first schedule produced a MST of greater than 1 1/2 years; the other schedules produced MSTs that were lower. It was determined that by applying a factor of 1.9, similar survival responses of normal rats were obtained with single as with fractionated radiation exposures. Animals burdened with 9L gliosarcoma brain tumors normally died of the disease process within 18 to 28 days ater tumor inoculation. Both single and fractionated radiation therapy resulted in a prolongation of survival of tumor-burdened rats. This prolongation was found to be linearly dependent upon the dose; but only minimally dependent upon the time after inoculation at which therapy was initiated, or upon the fractionation schedule that was used. As with normal animals, similar responses were obtained with single as with fractionated exposures when a factor (1.9) was applied. All tumor-bearing animals died prior to the time that death was observed in normal, irradiated rats. Thus, the 9L gliosarcoma rat brain tumor model can be used for the pre-clinical experimental investigation of new therapeutic schedules involving radiation therapy and adjuvant therapies

  15. Targeted radionuclide therapy for solid tumors: An overview

    International Nuclear Information System (INIS)

    De Nardo, Sally J.; De Nardo, Gerald L.

    2006-01-01

    Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma (NHL) as a single agent, solid tumors have shown less clinically significant therapeutic response to RIT alone. The clinical impact of RIT or other forms of targeted radionuclide therapy for solid tumors depends on the development of a high therapeutic index (TI) for the tumor vs. normal tissue effect, and the implementation of RIT as part of synergistic combined modality therapy (CMRIT). Preclinical and clinical studies have provided a wealth of information, and new prototypes or paradigms have shed light on future possibilities in many instances. Evidence suggests that combination and sequencing of RIT in CMRIT appropriately can provide effective treatment for many solid tumors. Vascular targets provide RIT enhancement opportunities and nanoparticles may prove to be effective carriers for RIT combined with intracellular drug delivery or alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence and timing of combined modality treatments will be of critical importance to achieve synergy for therapy while minimizing toxicity. Fortunately, the radionuclide used for RIT also provides a signal useful for nondestructive quantitation of the influence of sequence and timing of CMRIT on events in animals and patients. This can be readily accomplished clinically using quantitative high-resolution imaging (e.g., positron emission tomography [PET])

  16. Anti-tumor therapy with macroencapsulated endostatin producer cells.

    Science.gov (United States)

    Rodrigues, Danielle B; Chammas, Roger; Malavasi, Natália V; da Costa, Patrícia L N; Chura-Chambi, Rosa M; Balduino, Keli N; Morganti, Ligia

    2010-03-02

    Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. This study indicates that immunoisolation devices containing endostatin

  17. Hormone therapy in ovarian granulosa cell tumors: a systematic review

    NARCIS (Netherlands)

    van Meurs, Hannah S.; van Lonkhuijzen, Luc R. C. W.; Limpens, Jacqueline; van der Velden, Jacobus; Buist, Marrije R.

    2014-01-01

    This systematic review assessed the effectiveness of hormone therapy (HT) in patients with a granulosa cell tumor (GCT) of the ovary. Medline (OVID), EMBASE (OVID), the Cochrane Central Register of Controlled Trials (CENTRAL), prospective trial registers and PubMed (as supplied by publisher-subset)

  18. Movie prediction of lung tumor for precise chasing radiation therapy

    International Nuclear Information System (INIS)

    Chhatkuli, Ritu Bhusal; Demachi, Kazuyuki; Kawai, Masaki; Sakakibara, Hiroshi; Uesaka, Mitsuru

    2012-01-01

    In recent years, precision for radiation therapy is a major challenge in the field of cancer treatment. When it comes to a moving organ like lungs, limiting the radiation to the target and sparing the surrounding healthy tissue is always a concern. It can induce the limit in the accuracy of area irradiated during lung cancer radiation therapy. Many methods have been introduced to compensate the motion in order to reduce the effect of radiation to healthy tissue due to respiratory motion. The motion of lung along with the tumor makes it very difficult to spare the healthy tissue during radiation therapy. The fear of this unintended damage to the neighboring tissue often limits the dose that can be applied to the tumor. The purpose of this research is the prediction of future motion images for the improvement of tumor tracking method. We predict the motion images by using principal component analysis (PCA) and multi-channel singular spectral analysis (MSSA) method. Time series x-ray images are used as training images. The motion images were successfully predicted and verified using the developed algorithm. The real time implementation of this method in future is believed to be significant for higher level of real time tumor tracking during radiation therapy. (author)

  19. Radiation therapy of tumors of the oral cavity

    International Nuclear Information System (INIS)

    Parsons, J.T.; Million, R.R.

    1987-01-01

    Both operation and irradiation can cure a high percentage of patients with oral cavity carcinomas. The decision as to which modality is best (or whether to combine both modalities or offer only palliative treatment) in a particular patient is frequently complex and involves consideration of a number of factors before rational therapy can be planned. 1. Tumor location and distribution. 2. Tumor volume. 3. Tumor differentiation. 4. Known patterns of spread. 5. Functional, rehabilitative, and cosmetic aspects and their impact on the patient's life style and occupation. 6. The wishes of the patient and family. 7. Availability of a given treatment in the patient's geographic area. 8. Experience of the patient's physicians. 9. Anticipated cure rates with the various modes of therapy. 10. Expense. 11. The patient's age. 12. Tobacco and alcohol consumption. 13. Presence of other serious medical problems

  20. Image-based modeling of tumor shrinkage in head and neck radiation therapy1

    Science.gov (United States)

    Chao, Ming; Xie, Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing, Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth∕shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the “ground truth” with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy. PMID:20527569

  1. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    International Nuclear Information System (INIS)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei

    2010-01-01

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  2. Image-based modeling of tumor shrinkage in head and neck radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chao Ming; Xie Yaoqin; Moros, Eduardo G.; Le, Quynh-Thu; Xing Lei [Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 and Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States); Department of Radiation Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205-1799 (United States); Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, California 94305-5847 (United States)

    2010-05-15

    Purpose: Understanding the kinetics of tumor growth/shrinkage represents a critical step in quantitative assessment of therapeutics and realization of adaptive radiation therapy. This article presents a novel framework for image-based modeling of tumor change and demonstrates its performance with synthetic images and clinical cases. Methods: Due to significant tumor tissue content changes, similarity-based models are not suitable for describing the process of tumor volume changes. Under the hypothesis that tissue features in a tumor volume or at the boundary region are partially preserved, the kinetic change was modeled in two steps: (1) Autodetection of homologous tissue features shared by two input images using the scale invariance feature transformation (SIFT) method; and (2) establishment of a voxel-to-voxel correspondence between the images for the remaining spatial points by interpolation. The correctness of the tissue feature correspondence was assured by a bidirectional association procedure, where SIFT features were mapped from template to target images and reversely. A series of digital phantom experiments and five head and neck clinical cases were used to assess the performance of the proposed technique. Results: The proposed technique can faithfully identify the known changes introduced when constructing the digital phantoms. The subsequent feature-guided thin plate spline calculation reproduced the ''ground truth'' with accuracy better than 1.5 mm. For the clinical cases, the new algorithm worked reliably for a volume change as large as 30%. Conclusions: An image-based tumor kinetic algorithm was developed to model the tumor response to radiation therapy. The technique provides a practical framework for future application in adaptive radiation therapy.

  3. Proton therapy for tumors of the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Munzenrider, J.E.; Liebsch, N.J. [Dept. of Radiation Oncology, Harvard Univ. Medical School, Boston, MA (United States)

    1999-06-01

    Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

  4. Proton therapy for tumors of the skull base

    International Nuclear Information System (INIS)

    Munzenrider, J.E.; Liebsch, N.J.

    1999-01-01

    Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

  5. Trojan horse at cellular level for tumor gene therapies.

    Science.gov (United States)

    Collet, Guillaume; Grillon, Catherine; Nadim, Mahdi; Kieda, Claudine

    2013-08-10

    Among innovative strategies developed for cancer treatments, gene therapies stand of great interest despite their well-known limitations in targeting, delivery, toxicity or stability. The success of any given gene-therapy is highly dependent on the carrier efficiency. New approaches are often revisiting the mythic trojan horse concept to carry therapeutic nucleic acid, i.e. DNAs, RNAs or small interfering RNAs, to pathologic tumor site. Recent investigations are focusing on engineering carrying modalities to overtake the above limitations bringing new promise to cancer patients. This review describes recent advances and perspectives for gene therapies devoted to tumor treatment, taking advantage of available knowledge in biotechnology and medicine. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Efficacy of Surgical Therapy for Carotid Body Tumors

    Institute of Scientific and Technical Information of China (English)

    Li-shan Lian; Chang-wei Liu; Heng Guan; Yue-hong Zheng; Xing-ming Chen; Yong-jun Li

    2011-01-01

    Objective To evaluate the efficacy of surgical therapy for carotid body tumors.Methods A retrospective analysis was conducted,covering the diagnosis,surgical procedure,post-operative complications,and prognosis of 120 cases of carotid body tumors in Peking Union Medical College Hospital from 1949 to May,2011.Results Surgical excision was successfully performed in 111 cases with 117 tumors.In all those cases,50 underwent simple tumor resection,42 underwent resection of tumors and ligation of the external carotid arteries,7 underwent co-resection of tumors and common carotid arteries,internal carotid arteries,as well as external arteries without vascular reconstruction,and the other 12 cases experienced tumor resection and vascular reconstruction as internal carotid arteries were involved.After operation,3 cases developed cerebral infarction,30 cases showed cranial nerve palsy,including 15 cases of hypoglossal nerve damage,10 cases of vagus paralysis,and 5 cases of Horner's syndrome.Conclusion It is essential to make a proper surgical strategy,which can reduce postoperative complications.

  7. Age related changes in tumor vascularity

    International Nuclear Information System (INIS)

    Loerelius, L.E.; Stridbeck, H.

    1984-01-01

    VX 2 tumors in the rabbit hind leg were investigated at one, two and three weeks of age. Angiograms were compared with vascular casts. The tumors grew rapidly the first two weeks of age. Large variations in vascularity were noted between tumors of different ages. With increasing age arteriovenous shunts at the tumor periphery and areas of avascularity of necrosis in the tumor center increased in size. Possible reasons for tumor necrosis are increased tissue pressure, anoxia caused by arteriovenous shunts and elevation in venous pressure. The natural history of the VX 2 tumor must be considered in every experimental study of the effect of any treatment. (orig.)

  8. The Influence of Photodynamic Therapy on Tumor Cell S180

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    Pouran Sadat Tayebi

    2017-05-01

    Full Text Available Today cancer is the second important factor of the death in the world. Most of the cancer patients are treated with standard therapies, including surgery, radiation and/or chemotherapy. These standard therapies are most efficient on the primary tumor, but in the case of disseminated disease, they are often not effective. Treatment of disease that has disseminated from the primary tumor and metastasized to distant sites has promoted the investigation of immunotherapeutic strategies for cancer, and has been a major area of research over the last couple of decades. Chemotherapy and radiotherapy, standard therapies, are the main treatments for majority of cancer patients. Our studies demonstrate that ALA-HMME-PDT has a role in enhanced the quality of life and lengthens survival in mice infected by sarcoma 180. The reported method is hardly implemented but it possible in any clinical situation where PDT is needed. These therapies are most efficient in bearing the tumor in its first process of formation. Currently, the hot topic of discussion and research in the cancer arena is photodynamic Therapy (PDT. This type of therapy is an emerging channel of treatment that is very successful in eradicating cancer, with few side effects. The effectiveness of photodynamic therapy on the sarcoma treating process in mice by using ALA and HMME photosensitizers is investigated by this study. Many factors help us determine effectiveness of PDT including concentration of the sensitizer, absorption of light energy and accessibility of molecular oxygen in the target tissue during light irradiation, besides intrinsic sensitivity of target tissue.

  9. The inflammation markers in serum of tumor-bearing rats after plasmonic photothermal therapy

    Science.gov (United States)

    Bucharskaya, Alla B.; Maslyakova, Galina N.; Terentyuk, Georgy S.; Afanasyeva, Galina A.; Navolokin, Nikita A.; Zakharova, Natalia B.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.; Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, Valery V.

    2018-02-01

    We report on plasmonic photothermal therapy of rats with inoculated cholangiocarcinoma through the intratumoral injection of PEG-coated gold nanorods followed by CW laser light irradiation. The length and diameter of gold nanorods were 41+/-8 nm and 10+/-2 nm, respectively; the particle mass-volume concentration was 400 μg/mL, which corresponds to the optical density of 20 at the wavelength 808 nm. The tumor-bearing rats were randomly divided into three groups: (1) without any treatment (control); (2) with only laser irradiation of tumor; (3) with intratumoral administration of gold nanorods and laser irradiation of tumors. An hour before laser irradiation, the animals were injected intratumorally with gold nanorod solutions in the amount of 30% of the tumor volume. The infrared 808-nm laser with power density of 2.3 W/cm2 was used for plasmonic photothermal therapy (PTT). The withdraw of animals from the experiment was performed 24 h after laser exposure. The content of lipid peroxidation products and molecular markers of inflammation (TNF-α, IGF-1, VEGF-C) was determined by ELISA test in serum of rats. The standard histological techniques with hematoxylin and eosin staining were used for morphological examination of tumor tissues. It was revealed that the significant necrotic changes were noted in tumor tissue after plasmonic photothermal therapy, which were accompanied by formation of inflammatory reaction with release of proinflammatory cytokines and lipid peroxidation products into the bloodstream

  10. Sensitivity of MRI tumor biomarkers to VEGFR inhibitor therapy in an orthotopic mouse glioma model.

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    Christian T Farrar

    Full Text Available MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI and a slight decrease in the water apparent diffusion coefficient (ADC were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV, relative microvascular blood volume (rMBV, transverse relaxation time (T2, blood vessel permeability (K(trans, and extravascular-extracellular space (ν(e. The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.

  11. Tumor biology and cancer therapy – an evolving relationship

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    Lother Ulrike

    2009-08-01

    Full Text Available Abstract The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pathways underlie cancer, and not just altered genes. Thus, an effective therapeutic agent will sometimes have to target downstream parts of a signaling pathway or physiological effects rather than individual genes. In addition, over the past few years increasing evidence has suggested that solid tumors represent a very heterogeneous group of cells with different susceptibility to cancer therapy. Thus, since therapeutic concepts and pathophysiological understanding are continuously evolving a combination of current concepts in tumor therapy and tumor biology is needed. This review aims to present current problems of cancer therapy by highlighting exemplary results from recent clinical trials with colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying reasons.

  12. Boron neutron capture therapy: Brain Tumor Treatment Evaluation Program

    International Nuclear Information System (INIS)

    Griebenow, M.L.; Dorn, R.V. III; Gavin, P.R.; Spickard, J.H.

    1988-01-01

    The United States (US) Department of Energy (DOE) recently initiated a focused, multidisciplined program to evaluate Boron Neutron Capture Therapy (BNCT) for the treatment of brain tumors. The program, centered at the DOE/endash/Idaho National Engineering Laboratory (INEL), will develop the analytical, diagnostic and treatment tools, and the database required for BNCT technical assessment. The integrated technology will be evaluated in a spontaneously-occurring canine brain-tumor model. Successful animal studies are expected to lead to human clinical trials within four to five years. 2 refs., 3 figs

  13. Non-invasive pre-clinical MR imaging of prostate tumor hypoxia for radiation therapy prognosis

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    Derek White

    2014-03-01

    Full Text Available Purpose: To investigate the usefulness of Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI changes in signal intensity related to oxygen challenge for predicting tumor response to radiation therapy.Methods: Dynamic MR signal changes were acquired using Varian 4.7T small animal MR scanner prior to image-guided radiation therapy (IGRT of small (n = 6 and large subcutaneous (n = 5 prostate tumors in adult male rats. An interleaved blood-oxygen level dependent (BOLD and tissue-oxygen level dependent (TOLD data acquisition or (IBT was performed using a baseline of medical air as positive control and using medical oxygen as a breathing challenge. BOLD used a 2-D multi-slice spoiled gradient-echo with multi-echo sequence. TOLD used a 2-D multi-slice spoiled gradient-echo sequence. Voxel changes in signal intensity were determined by a correlation coefficient mapping technique. Irradiation technique planned consisted of 1F × 15 Gy AP/PA or 2F × 7.5 Gy AP/PA to the gross tumor volume (GTV. Tumor growth measurements were recorded over time to assess the response to IGRT.Results: BOLD and TOLD signals variously illustrated positive or negative impulse responses in the tumor ROI due to inhaling medical oxygen. Correlation coefficient mapping demonstrated heterogeneity in tumors after inhaling medical oxygen. BOLD and TOLD signals exhibited increased changes in signal intensities after the first fraction of dose. Multi-fractionation had minimum effect until the second fraction of dose was applied. Tumor growth delays were observed when inhaling medical oxygen during IGRT.Conclusion: OE-MRI is a non-invasive imaging modality that can provide insight to the oxygen status of tumors. Observed increase percent changes in BOLD and TOLD signal intensities after the first fraction of dose suggest tumors experienced reoxygenation. OE-MRI could be used for predicting tumor response to IGRT when using medical oxygen for increasing GTV radiosensitivity, suggesting

  14. Change of tumor vascular reactivity during tumor growth and postchemotherapy observed by near-infrared spectroscopy

    Science.gov (United States)

    Lee, Songhyun; Jeong, Hyeryun; Seong, Myeongsu; Kim, Jae Gwan

    2017-12-01

    Breast cancer is one of the most common cancers in females. To monitor chemotherapeutic efficacy for breast cancer, medical imaging systems such as x-ray mammography, computed tomography, magnetic resonance imaging, and ultrasound imaging have been used. Currently, it can take up to 3 to 6 weeks to see the tumor response from chemotherapy by monitoring tumor volume changes. We used near-infrared spectroscopy (NIRS) to predict breast cancer treatment efficacy earlier than tumor volume changes by monitoring tumor vascular reactivity during inhalational gas interventions. The results show that the amplitude of oxy-hemoglobin changes (vascular reactivity) during hyperoxic gas inhalation is well correlated with tumor growth and responded one day earlier than tumor volume changes after chemotherapy. These results may imply that NIRS with respiratory challenges can be useful in early detection of tumor and in the prediction of tumor response to chemotherapy.

  15. Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

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    Eric C. Woolf

    2016-11-01

    Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  16. Dysregulated pH in Tumor Microenvironment Checkmates Cancer Therapy

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    Jaleh Barar

    2013-12-01

    Full Text Available Introduction: The dysregulation of pH by cancerous cells of solid tumors is able to create a unique milieu that is in favor of progression, invasion and metastasis as well as chemo-/immuno-resistance traits of solid tumors. Bioelements involved in pH dysregulation provide new set of oncotargets, inhibition of which may result in better clinical outcome. Methods: To study the impacts of pH dysregulation, we investigated the tumor development and progression in relation with Warburg effect, glycolysis and formation of aberrant tumor microenvironment. Results: The upregulation of glucose transporter GLUT-1 and several enzymes involve in glycolysis exacerbates this phenomenon. The accumulation of lactic acids in cancer cells provokes upregulation of several transport machineries (MCT-1, NHE-1, CA IX and H+ pump V-ATPase resulting in reinforced efflux of proton into extracellular fluid. This deviant event makes pH to be settled at 7.4 and 6.6 respectively in cancer cells cytoplasm and extracellular fluid within the tumor microenvironment, which in return triggers secretion of lysosomal components (various enzymes in acidic milieu with pH 5 into cytoplasm. All these anomalous phenomena make tumor microenvironment (TME to be exposed to cocktail of various enzymes with acidic pH, upon which extracellular matrix (ECM can be remodeled and even deformed, resulting in emergence of a complex viscose TME with high interstitial fluid pressure. Conclusion: It seems that pH dysregulation is able to remodel various physiologic functions and make solid tumors to become much more invasive and metastatic. It also can cause undesired resistance to chemotherapy and immunotherapy. Hence, cancer therapy needs to be reinforced using specific inhibitors of bioelements involved in pH dysregulation of TME in solid tumors.

  17. Overcoming tumor resistance by heterologous adeno-poxvirus combination therapy

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    Markus Vähä-Koskela

    2014-01-01

    Full Text Available Successful cancer control relies on overcoming resistance to cell death and on activation of host antitumor immunity. Oncolytic viruses are particularly attractive in this regard, as they lyse infected tumor cells and trigger robust immune responses during the infection. However, repeated injections of the same virus promote antiviral rather than antitumor immunity and tumors may mount innate antiviral defenses to restrict oncolytic virus replication. In this article, we have explored if alternating the therapy virus could circumvent these problems. We demonstrate in two virus-resistant animal models a substantial delay in antiviral immune- and innate cellular response induction by alternating injections of two immunologically distinct oncolytic viruses, adenovirus, and vaccinia virus. Our results are in support of clinical development of heterologous adeno-/vaccinia virus therapy of cancer.

  18. Boron compounds in neutron capture therapy of tumors

    International Nuclear Information System (INIS)

    Strouf, O.; Gregor, V.

    1986-01-01

    In the selective incorporation of a sufficient amount of a compound containing boron isotope 10 B in the tumor tissue for neutron capture therapy, high efficiency is achieved in tumor destruction while sparing the surrounding tissues. In the treatment of brain tumors, 4-carboxy phenylboric acid and the disodium salt of mercaptoundecahydrododecaborate were successfully tested. The use of the compounds minimizes radiation damage to the blood stream of the brain. In case of melanomas the L-DOPA-borate complex, boronophenylalanine and chlorpromazine preparations containing 10 B are used. In the treatment of cancer of the reproductive organs, boron derivatives of estradiol and testosterone have been proven. The immunobiological procedure, i.e., the use of antibodies with bound boron compounds, is being intensively studied. (M.D.)

  19. 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)

  20. Clinical results of radiation therapy for thymic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, Masaji; Fushiki, Masato

    1991-12-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author).

  1. Clinical results of radiation therapy for thymic tumors

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki; Takahashi, Masaji; Fushiki, Masato.

    1991-01-01

    From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author)

  2. OFFICIAL MEDICATIONS FOR ANTI-TUMOR GENE THERAPY

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    E. R. Nemtsova

    2016-01-01

    Full Text Available This is a review of modern literature data of official medications for anti-tumor gene therapy as well as of medications that finished clinical trials.The article discusses the concept of gene therapy, the statistical analysis results of initiated clinical trials of gene products, the most actively developing directions of anticancer gene therapy, and the characteristics of anti-tumor gene medications.Various delivery systems for gene material are being examined, including viruses that are defective in  replication (Gendicine™ and Advexin and oncolytic (tumor specific conditionally replicating viruses (Oncorine™, ONYX-015, Imlygic®.By now three preparations for intra-tumor injection have been introduced into oncology clinical practice: two of them – Gendicine™ and Oncorine™ have been registered in China, and one of them – Imlygic® has been registered in the USA. Gendicine™ and Oncorine™ are based on the wild type p53 gene and are designed for treatment of patients with head and neck malignancies. Replicating adenovirus is the delivery system in Gendicine™, whereas oncolytic adenovirus is the vector for gene material in Oncorine™. Imlygic® is based on the  recombinant replicating HSV1 virus with an introduced GM–CSF gene and is designed for treatment of  melanoma patients. These medications are well tolerated and do not cause any serious adverse events. Gendicine™ and Oncorine™ are not effective in monotherapy but demonstrate pronounced synergism with chemoand radiation therapy. Imlygic® has just started the post marketing trials.

  3. Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.

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    Reinhard Meier

    Full Text Available Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13, Avastin (n = 6 or PBS (n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.

  4. 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.

  5. Image changes of the cases with neuroblastoma observed without therapy

    International Nuclear Information System (INIS)

    Takeuchi, Maho; Aida, Noriko

    1999-01-01

    Fifteen cases (10 males and 5 females) of neuroblastoma diagnosed by mass screening from November 1993 to October 1997, were observed without therapy. The mean age was 7.9 months. There were tumors in para-aortic area in 4 cases, in adrenal parts in 7 cases, in mediastinum in 3 cases. The other case had tumors in mediastinum and adrenal parts, bilaterally. The observation was executed by the ultrasonography in cases with the abdominal tumor and by MRI in cases with the mediastinal tumor. CT, MRI and US were performed in the first examination by radiologist. MIBG scintigraphy was used mainly for the detection of distant metastases. Imaging was performed at every one or two months in the beginning of observation, and at every three or four months afterwards. Tumors reduced in 9 cases, unchanged in 1 case and increased in 5 cases (8 tumors). The change of tumor size could be evaluated accurately, but the prediction of benignity or malignancy was difficult. Pathological findings were obtained from 5 cases who underwent surgical resection. Four cases had increased tumor. Two of them had benign neuroblastoma or ganglioma, and 2 cases had malignant neuroblastoma of low differentiation. One case with decreased tumor had neuroblastoma and became benign. (K.H.)

  6. Anti-tumor therapy with macroencapsulated endostatin producer cells

    Directory of Open Access Journals (Sweden)

    Balduino Keli N

    2010-03-01

    Full Text Available Abstract Background Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Results Mice were inoculated subcutaneously with melanoma (B16F10 cells or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. Conclusions This study indicates that

  7. Tumor microenvironmental changes induced by the sulfamate carbonic anhydrase IX inhibitor S4 in a laryngeal tumor model.

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    Tineke W H Meijer

    Full Text Available BACKGROUND AND PURPOSE: Carbonic anhydrase IX (CAIX plays a pivotal role in pH homeostasis, which is essential for tumor cell survival. We examined the effect of the CAIX inhibitor 4-(3'(3",5"-dimethylphenyl-ureidophenyl sulfamate (S4 on the tumor microenvironment in a laryngeal tumor model by analyzing proliferation, apoptosis, necrosis, hypoxia, metabolism and CAIX ectodomain shedding. METHODS: SCCNij202 tumor bearing-mice were treated with S4 for 1, 3 or 5 days. CAIX ectodomain shedding was measured in the serum after therapy. Effects on tumor cell proliferation, apoptosis, necrosis, hypoxia (pimonidazole and CAIX were investigated with quantitative immunohistochemistry. Metabolic transporters and enzymes were quantified with qPCR. RESULTS: CAIX ectodomain shedding decreased after treatment with S4 (p<0.01. S4 therapy did neither influence tumor cell proliferation nor the amount of apoptosis and necrosis. Hypoxia (pimonidazole and CAIX expression were also not affected by S4. CHOP and MMP9 mRNA as a reference of intracellular pH did not change upon treatment with S4. Compensatory mechanisms of pH homeostasis at the mRNA level were not observed. CONCLUSION: As the clinical and biological meaning of the decrease in CAIX ectodomain shedding after S4 therapy is not clear, studies are required to elucidate whether the CAIX ectodomain has a paracrine or autocrine signaling function in cancer biology. S4 did not influence the amount of proliferation, apoptosis, necrosis and hypoxia. Therefore, it is unlikely that S4 can be used as single agent to influence tumor cell kill and proliferation, and to target primary tumor growth.

  8. Awake Craniotomy for Tumor Resection: Further Optimizing Therapy of Brain Tumors.

    Science.gov (United States)

    Mehdorn, H Maximilian; Schwartz, Felix; Becker, Juliane

    2017-01-01

    In recent years more and more data have emerged linking the most radical resection to prolonged survival in patients harboring brain tumors. Since total tumor resection could increase postoperative morbidity, many methods have been suggested to reduce the risk of postoperative neurological deficits: awake craniotomy with the possibility of continuous patient-surgeon communication is one of the possibilities of finding out how radical a tumor resection can possibly be without causing permanent harm to the patient.In 1994 we started to perform awake craniotomy for glioma resection. In 2005 the use of intraoperative high-field magnetic resonance imaging (MRI) was included in the standard tumor therapy protocol. Here we review our experience in performing awake surgery for gliomas, gained in 219 patients.Patient selection by the operating surgeon and a neuropsychologist is of primary importance: the patient should feel as if they are part of the surgical team fighting against the tumor. The patient will undergo extensive neuropsychological testing, functional MRI, and fiber tractography in order to define the relationship between the tumor and the functionally relevant brain areas. Attention needs to be given at which particular time during surgery the intraoperative MRI is performed. Results from part of our series (without and with ioMRI scan) are presented.

  9. Combination therapy with gefitinib and doxorubicin inhibits tumor growth in transgenic mice with adrenal neuroblastoma

    International Nuclear Information System (INIS)

    Kawano, Kumi; Hattori, Yoshiyuki; Iwakura, Hiroshi; Akamizu, Takashi; Maitani, Yoshie

    2013-01-01

    Highly relevant mouse models of human neuroblastoma (NB) are needed to evaluate new therapeutic strategies against NB. In this study, we characterized transgenic mice with bilateral adrenal tumors. On the basis of information from the tumoral gene expression profiles, we examined the antitumor effects of unencapsulated and liposomal doxorubicin (DXR), alone and in combination with gefitinib, on adrenal NB. We showed that intravenous injection of unencapsulated or liposomal DXR alone inhibited tumor growth in a dose-dependent manner, as assessed by magnetic resonance imaging (MRI). However, liposomal DXR did not exhibit greater antitumor effect than unencapsulated DXR. Immunohistochemical analysis revealed that the adrenal tumor vasculature with abundant pericyte coverage was a less leaky structure for liposomes. Combination therapy with unencapsulated or liposomal DXR plus gefitinib strongly suppressed tumor growth and delayed tumor regrowth than treatment with unencapsulated or liposomal DXR alone, even at a lower dose of DXR. Dynamic contrast-enhanced MRI analysis revealed that gefitinib treatment increased blood flow in the tumor, indicating that gefitinib treatment changes the tumor vascular environment in a manner that may increase the antitumor effect of DXR. In conclusion, the combination of gefitinib and DXR induces growth inhibition of adrenal NBs in transgenic mice. These findings will provide helpful insights into new treatments for NB

  10. Modeling the oxygen microheterogeneity of tumors for photodynamic therapy dosimetry

    Science.gov (United States)

    Pogue, Brian W.; Paulsen, Keith D.; O'Hara, Julia A.; Hoopes, P. Jack; Swartz, Harold

    2000-03-01

    Photodynamic theory of tumors uses optical excitation of a sensitizing drug within tissue to produce large deposits of singlet oxygen, which are thought to ultimately cause the tumor destruction. Predicting dose deposition of singlet oxygen in vivo is challenging because measurement of this species in vivo is not easily achieved. But it is possible to follow the concentration of oxygen in vivo, and so measuring the oxygen concentration transients during PDT may provide a viable method of estimating the delivered dose of singlet oxygen. However modeling the microscopic heterogeneity of the oxygen distribution within a tumor is non-trivial, and predicting the microscopic dose deposition requires further study, but this study present the framework and initial calibration needed or modeling oxygen transport in complex geometries. Computational modeling with finite elements provides a versatile structure within which oxygen diffusion and consumption can be modeled within realistic tissue geometries. This study develops the basic tools required to simulate a tumor region, and examines the role of (i) oxygen supply and consumption rates, (ii) inter- capillary spacing, (iii) photosensitizer distribution, and (iv) differences between simulated tumors and those derived directly from histology. The result of these calculations indicate that realistic tumor tissue capillary networks can be simulated using the finite element method, without excessive computational burden for 2D regions near 1 mm2, and 3D regions near 0.1mm3. These simulations can provide fundamental information about tissue and ways to implement appropriate oxygen measurements. These calculations suggest that photodynamic therapy produces the majority of singlet oxygen in and near the blood vessels, because these are the sites of highest oxygen tension. These calculations support the concept that tumor vascular regions are the major targets for PDT dose deposition.

  11. Monitoring early tumor response to drug therapy with diffuse optical tomography

    Science.gov (United States)

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

  12. Clinical considerations for neutron capture therapy of brain tumors

    International Nuclear Information System (INIS)

    Madoc-Jones, H.; Wazer, D.E.; Zamenhof, R.G.; Harling, O.K.; Bernard, J.A. Jr.

    1990-01-01

    The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the US in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should not be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam cases gamma rays to be generated when it interacts with tissue, they think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue

  13. Predictive Biomarkers for Bevacizumab in Anti-tumor Therapy

    Directory of Open Access Journals (Sweden)

    Qingqing PAN

    2011-07-01

    Full Text Available Bevacizumab, the monoclonal antibody of vascular endothelial growth factor (VEGF has been applied to the therapy of several neoplasms, but an appropriate biomarker to predict the efficacy has not been found. Those markers can originate from peripheral circulation, tumor tissue and genes. Some researches have found that low level of vascular cell adhesion molecule-1 (VCAM-1, E-selectin, angiopoietin 2 (Ang-2 in circulation or carbonic anhydrase 9 (CA9, CD31-microvessel density (CD31-MVD in tumor tissue can predict better activity of bevacizumab. Moreover, high level of soluble VEGFR2 (sVEGFR2 in circulation or the ratio of phosphorylated-VEGFR2 (p-VEGFR2 and VEGFR2 in tumor tissue increasing has the same predictive function. As to the gene, VEGF-634 CC, VEGF-1498 TT and VEGFR2 H472Q are only related to the side effct. Thus more clinical tirals and basic researches should be performed to find out effective biomarkers in bevacizumab’s therapy.

  14. Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy

    Directory of Open Access Journals (Sweden)

    Xiang-Hong Peng

    2008-10-01

    Full Text Available Xiang-Hong Peng1,4, Ximei Qian2,4, Hui Mao3,4, Andrew Y Wang5, Zhuo (Georgia Chen1,4, Shuming Nie2,4, Dong M Shin1,4*1Department of Medical Oncology/Hematology; 2Department of Biomedical Engineering; 3Department of Radiology; 4Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 5Ocean Nanotech, LLC, Fayetteville, AR, USAAbstract: Magnetic iron oxide (IO nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI, which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.Keywords: iron oxide nanoparticles, tumor imaging, MRI, therapy

  15. The value of radiation therapy for pituitary tumors

    International Nuclear Information System (INIS)

    Watari, Tsutomu

    1995-01-01

    Following points are discussed in this review. 1) Historical review of our previous therapeutic management. 2) Classification of pituitary adenomas. 3) Clinical analysis of my recent 58 cases. 4) Verification of usefulness of postoperative irradiation which achieved to increase in local control rate. 5) Authoritativeness of radiotherapy. In general, 3 to 4 portal technique or arc therapy were employed. The lateral opposing field technique was avoid to use. The recommended doses using linear accelerator x-ray technique is approximately 5000 cGy in 5 weeks. To prevent radiation hazard; (1) examiner should not use technique of two opposed fields, (2) total doses should not exceed 5000 cGy in 5 to 6 weeks and the use of daily fractions should not exceed 200 cGy. 6) Correlation of hormone secreting tumors and radiation therapy. 7) Problem of radiosurgery and heavy particle. 8) Countermeasure for recurrence cases. 9) Problem of side effects of radiotherapy and its precaution. Complication of radiation for pituitary adenoma found that the significant side effects are negligibly small in recent years. 10) Pituitary tumor are originally slow growing and benign tumor, therefore the response to irradiation takes long time to elapse for final evaluation. For instance, over 80 to 90% of acromegaly patients respond HGH successfully, but this may require from one to several years. 11) Conclusion. (author)

  16. The value of radiation therapy for pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Watari, Tsutomu [Dokkyo Univ., Mibu, Tochigi (Japan). School of Medicine

    1995-09-01

    Following points are discussed in this review. (1) Historical review of our previous therapeutic management. (2) Classification of pituitary adenomas. (3) Clinical analysis of my recent 58 cases. (4) Verification of usefulness of postoperative irradiation which achieved to increase in local control rate. (5) Authoritativeness of radiotherapy. In general, 3 to 4 portal technique or arc therapy were employed. The lateral opposing field technique was avoid to use. The recommended doses using linear accelerator x-ray technique is approximately 5000 cGy in 5 weeks. To prevent radiation hazard; (1) examiner should not use technique of two opposed fields, (2) total doses should not exceed 5000 cGy in 5 to 6 weeks and the use of daily fractions should not exceed 200 cGy. (6) Correlation of hormone secreting tumors and radiation therapy. (7) Problem of radiosurgery and heavy particle. (8) Countermeasure for recurrence cases. (9) Problem of side effects of radiotherapy and its precaution. Complication of radiation for pituitary adenoma found that the significant side effects are negligibly small in recent years. (10) Pituitary tumor are originally slow growing and benign tumor, therefore the response to irradiation takes long time to elapse for final evaluation. For instance, over 80 to 90% of acromegaly patients respond HGH successfully, but this may require from one to several years. (11) Conclusion. (author).

  17. Gadolinium neutron capture therapy for brain tumors. Biological aspects

    International Nuclear Information System (INIS)

    Takagaki, Masao; Oda, Yoshifumi; Matsumoto, Masato; Kikuchi, Haruhiko; Kobayashi, Tooru; Kanda, Keiji; Ujeno, Yowri.

    1994-01-01

    This study investigated the tumoricidal effect of gadolinium neutron capture therapy (Gd-NCT) in in vitro and in vivo systems using Gd-DTPA. In in vitro study, a certain amount of Gd-DTPA, yielding 5000 ppm Gd-n, was added to human glioma cells, T98G, upon which thermal neutrons were exposed. After irradiation, the cells were incubated and the colonies were counted 10 days later. In in vivo study, Fisher-344 rats with experimentally induced gliosarcoma cells (9L) were exposed to thermal neutrons at a fluence rate of 3E+9/s for 1 h immediately after iv injection of Gd-DTPA. Two weeks after irradiation, brain samples were histologically examined. Tumor clearance of Gd-DTPA was also determined. In vitro analysis showed that a 1% survival level was obtained at 3.75E+12 (n/cm 2 ) for the Gd (+) medium and 2.50E+13 (n/cm 2 ) for the Gd (-) medium. In in vivo analysis, the concentration of Gd in 9L-rat brain tumor after iv injection of 0.2 mg/kg Gd-DTPA was found to be less than 100 ppm, but Gd-NCT on 9L-rat brain tumor administered with a ten-fold dose showed a substantial killing effect on tumor without serious injury to the normal brain structure. The killing effect of Gd-NCT was confirmed in in vitro and in vivo systems. (N.K.)

  18. Targeting sarcoma tumor-initiating cells through differentiation therapy

    Directory of Open Access Journals (Sweden)

    Dan Han

    2017-05-01

    Full Text Available Human leukocyte antigen class I (HLA-I down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation.

  19. Boron neutron capture therapy for malignant brain tumor in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Yoshinobu [National Kagawa Children`s Hospital, Takamatsu, Kagawa (Japan)

    1998-03-01

    Since 1968, we have treated 149 patients and performed boron-neutron capture therapy (BNCT) on 164 occasions using 5 reactors in Japan. There were 64 patients with glioblastoma, 39 patients with anaplastic astrocytoma and 17 patients with low grade astrocytoma (grade 1 or 2). There were 30 patients with other types of tumor. The overall response rate in the glioma patients was 64%. Seven patients (12%) of glioblastoma, 22 patients (56%) of anaplastic astrocytoma and 8 patients (62%) of low grade astrocytoma lived more than 2 years Median survival time of glioblastoma was 640 days. Median survival times of patients with anaplastic astrocytoma was 1811 days, and 1669 days in low grade astrocytoma. Six patients (5 glioblastoma and one anaplastic astrocytoma) died within 90 days after BNCT. Six patients lived more than 10 years. Histological grading, age of the patients, neutron fluence at the target point and target depth or size of the tumor were proved to be important factors. BNCT is an effective treatment for malignant brain tumors. We are now became able to radiate the tumor more correctly with a high enough dose of neutron beam even if we use thermal neutron beam. (author)

  20. Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma

    Directory of Open Access Journals (Sweden)

    Ruman Rahman

    2010-01-01

    Full Text Available Despite advances in surgery, radiation therapy, and chemotherapeutics, patients with malignant glioma have a dismal prognosis. The formations of aberrant tumour vasculature and glioma cell invasion are major obstacles for effective treatment. Angiogenesis is a key event in the progression of malignant gliomas, a process involving endothelial cell proliferation, migration, reorganization of extracellular matrix and tube formation. Such processes are regulated by the homeostatic balance between proangiogenic and antiangiogenic factors, most notably vascular endothelial growth factors (VEGFs produced by glioma cells. Current strategies targeting VEGF-VEGF receptor signal transduction pathways, though effective in normalizing abnormal tumor vasculature, eventually result in tumor resistance whereby a highly infiltrative and invasive phenotype may be adopted. Here we review recent anti-angiogenic therapy for malignant glioma and highlight implantable devices and nano/microparticles as next-generation methods for chemotherapeutic delivery. Intrinsic and adaptive modes of glioma resistance to anti-angiogenic therapy will be discussed with particular focus on the glioma stem cell paradigm.

  1. 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...

  2. Photoradiation therapy of animal tumors and nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zhao, S.P.; Tao, Z.D.; Xiao, J.Y.; Peng, Y.Y.; Yang, Y.H.; Zeng, Q.S.; Liu, Z.W.

    1990-01-01

    Both animal tumors and human nasopharyngeal carcinoma were submitted to a photoradiation therapy (PRT) trial in order to determine the efficacy and side effects of PRT, as well as to elucidate its mechanism of cytotoxicity. In animal tumors, the inhibition rate was 70%, and of 20 patients, eight achieved complete remission, and ten, significant remission, with an overall response rate of 90%. The blood picture and the values of serum IgG, IgM, IgA, and C3 all remained stable post-PRT. Only three patients developed mild generalized skin photosensitive reactions, and these did not affect subsequent treatment. There was no immunosuppressive effect as evidenced by a tritium-labeled thymidine-incorporated lymphocytoblast transformation assay performed both before and after PRT. Ultrastructural studies at different time intervals after PRT highly suggested that the mitochondria and rough endoplasmic reticulum were among the first organelles to be damaged

  3. Synergistic gene and drug tumor therapy using a chimeric peptide.

    Science.gov (United States)

    Han, Kai; Chen, Si; Chen, Wei-Hai; Lei, Qi; Liu, Yun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2013-06-01

    Co-delivery of gene and drug for synergistic therapy has provided a promising strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and fabricated. As a drug carrier, the micelles self-assembled from the peptide exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH 7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily mediate transfection of pGL-3 reporter plasmid with or without the existence of serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability of peptide/DNA complexes was investigated by confocal laser scanning microscopy (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the peptide micelles to form micelleplexes during the self-assembly of the peptide. Cellular uptake and intracellular delivery of gene and drug were studied by CLSM and flow cytometry respectively. And p53 protein expression was determined via Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition effect were also studied. Results suggest that the co-delivery of gene and drug from peptide micelles resulted in effective cell growth inhibition in vitro and significant tumor growth restraining in vivo. The chimeric peptide-based gene and drug co-delivery system will find great potential for tumor therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. The long-term side effects of radiation therapy for benign brain tumors in adults

    International Nuclear Information System (INIS)

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R.

    1990-01-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs

  5. The long-term side effects of radiation therapy for benign brain tumors in adults

    Energy Technology Data Exchange (ETDEWEB)

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. (Univ. of Mississippi Medical Center, Jackson (USA))

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  6. Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

    Science.gov (United States)

    Han, Kai; Zhang, Jin; Zhang, Weiyun; Wang, Shibo; Xu, Luming; Zhang, Chi; Zhang, Xianzheng; Han, Heyou

    2017-03-28

    Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

  7. Changing Epidemiology of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-07-01

    Full Text Available Neurosurgeons at the Hospital for Sick Children, Toronto, Canada, analyzed and classified 1, 866 surgical pathology cases of brain tumors in children under age 19 years, treated 1980-2008.

  8. Glucocorticoid treatment of brain tumor patients: changes of apparent diffusion coefficient values measured by MR diffusion imaging

    International Nuclear Information System (INIS)

    Minamikawa, Sosuke; Kono, Kinuko; Nakayama, Keiko; Yokote, Hiroyuki; Tashiro, Takahiko; Inoue, Yuichi; Nishio, Akimasa; Hara, Mitsuhiro

    2004-01-01

    Glucocorticoids (GCC) generally are administered to patients with brain tumors to relieve neurological symptoms by decreasing the water content in a peritumoral zone of edema. We hypothesized that diffusion imaging and apparent diffusion coefficient (ADC) values could detect subtle changes of water content in brain tumors and in peritumoral edema after GCC therapy. The study consisted of 13 patients with intra-axial brain tumor, and ADC was measured in the tumor, within peritumoral edema, and in normal white matter remote from the tumor before and after GCC therapy. ADC also was measured in normal white matter in four control patients with no intracranial disease who were treated with GCC for other indications. Conventional MR images showed no visually evident interval change in tumor size or the extent of peritumoral edema in any subject after GCC therapy, which nonetheless resulted in a decrease in mean ADC of 7.0% in tumors (P 0.05, not significant) and 5.8% in normal white matter (P<0.05). In patients with no intracranial disease, GCC therapy decreased mean ADC in white matter by 5.4% (P<0.05). ADC measurement can demonstrate subtle changes in the brain after GCC therapy that cannot be observed by conventional MR imaging. Measurement of ADC proved to be a sensitive means of assessing the effect of GCC therapy, even in the absence of visually discernible changes in conventional MR images. (orig.)

  9. Effect of lymphokine-activated killer cells with or without radiation therapy against malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Kunio; Kamezaki, Takao; Shibata, Yasushi; Tsunoda, Takashi; Meguro, Kotoo; Nose, Tadao [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

    1995-01-01

    The use of autologous lymphokine-activated killer (LAK) cells to treat malignant brain tumors was evaluated in 10 patients, one with metastatic malignant melanoma and nine with malignant glioma. LAK cells were obtained by culturing autologous peripheral blood lymphocytes with human recombinant interleukin-2 (rIL-2) for 7-28 days. All patients underwent surgery to remove as much tumor as possible and an Ommaya reservoir was implaced in the tumor cavity. Two of the 10 patients had received radiotherapy elsewhere, so were treated with LAK cells alone. Eight patients were treated with a combination of LAK cells and radiotherapy, using 1.8-2.0 Gy fractions given five times a week with a total dosage between 54 and 65 Gy. LAK cells and rIL-2 were injected to the tumor cavity via the Ommaya reservoir once a week for inpatients and once a month for outpatients. The duration of the LAK therapy ranged from 3 to 23 months (mean 13.7 mos). Neuroimaging evaluation revealed two complete responses, three partial responses, four no changes, and one progressive disease. In one patient with pontine glioma, the Karnofsky performance score was raised from 20 to 60. There were no side effects after the injection of LAK cells and rIL-2. The results suggest low-dose LAK therapy is a useful and safe treatment modality for malignant brain tumors. (author).

  10. Advancement of researches on the malignant tumor radio-genetic therapy

    International Nuclear Information System (INIS)

    Tian Yue; Su Chenghai

    2008-01-01

    Radiotherapy is one of the routine methods of malignant tumor treatment and used in clinical many years, while gene therapy is one of the new therapy. But the formation of tumor is the complicated process effected by many factors and many genes. The effect of polygene therapy is not ideal. Therefore, radio-genetic therapy is the hot spot of the present study and will become one of the important direction of cancer therapy. (authors)

  11. Molecular Imaging of Gene Expression and Efficacy following Adenoviral-Mediated Brain Tumor Gene Therapy

    Directory of Open Access Journals (Sweden)

    Alnawaz Rehemtulla

    2002-01-01

    Full Text Available Cancer gene therapy is an active area of research relying upon the transfer and subsequent expression of a therapeutic transgene into tumor cells in order to provide for therapeutic selectivity. Noninvasive assessment of therapeutic response and correlation of the location, magnitude, and duration of transgene expression in vivo would be particularly useful in the development of cancer gene therapy protocols by facilitating optimization of gene transfer protocols, vector development, and prodrug dosing schedules. In this study, we developed an adenoviral vector containing both the therapeutic transgene yeast cytosine deaminase (yCD along with an optical reporter gene (luciferase. Following intratumoral injection of the vector into orthotopic 9L gliomas, anatomical and diffusion-weighted MR images were obtained over time in order to provide for quantitative assessment of overall therapeutic efficacy and spatial heterogeneity of cell kill, respectively. In addition, bioluminescence images were acquired to assess the duration and magnitude of gene expression. MR images revealed significant reduction in tumor growth rates associated with yCD/5-fluorocytosine (5FC gene therapy. Significant increases in mean tumor diffusion values were also observed during treatment with 5FC. Moreover, spatial heterogeneity in tumor diffusion changes were also observed revealing that diffusion magnetic resonance imaging could detect regional therapeutic effects due to the nonuniform delivery and/or expression of the therapeutic yCD transgene within the tumor mass. In addition, in vivo bioluminescence imaging detected luciferase gene expression, which was found to decrease over time during administration of the prodrug providing a noninvasive surrogate marker for monitoring gene expression. These results demonstrate the efficacy of the yCD/5FC strategy for the treatment of brain tumors and reveal the feasibility of using multimodality molecular and functional imaging

  12. Photodynamic therapy platform for glioblastoma and intrabronchial tumors

    Science.gov (United States)

    Orsila, Lasse; Alanko, Jukka-Pekka; Kaivosoja, Visa; Uibu, Toomas

    2018-02-01

    Photodynamic therapy (PDT) is bringing new, effective, and less invasive, possibilities for cancer treatment. ML7710 (Modulight Inc.) medical laser system offers a platform for performing PDT for multiple indications and drugs. Latest avenue is glioblastoma treatment with 5-Aminolevulinic acid (ALA-5) and 635-nm light, where clinical trials are about to begin. Preliminary work suggests major advantages in treatment control, including active in-situ feedback. ML7710 platform has already proven itself for clinical work with intrabronchial obstructive tumors. Preliminary result with 10 patients show that intrabronchial tumors, that strongly affect both the survival and the performance of the patient, can be significantly reduced with ML7710 operated at 665 nm and sodium chlorine E6 photosensitizer. The aim in most of the patients has been a palliative recanalization of the bronchial lumen in order to alleviate the symptoms such as breathlessness and hemoptysis. The illumination dose for the target area was 50-75 J/cm2. All the patients have received multimodality cancer treatment using other intrabronchial interventions, radiotherapy and chemotherapy as needed. In most of the patients, satisfactory treatment results were achieved and it was possible to restart chemotherapy in several patients. In one patient with local cancer a complete remission was established. PDT has also the advantage that it is possible to give PDT after a maximum dose of radiation therapy has already been used and fewer side effects if used in locally advanced intraluminar lung cancer.

  13. Holmium-166-chico intracavitary radiation therapy for cystic brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, C. H.; Lee, S. H.; Jang, J. S.; Kim, E. H.; Choi, C. W.; Hong, S. W.; Lim, S. M. [Korea Cancer Center, Seoul (Korea, Republic of)

    1997-07-01

    Holmium-166-chitosan complex (Ho-166-chico) is injected into the unresectable seven cystic brain tumors (2 cases of metastatic brain tumors from lung cancer, 1 case of recurrent trigeminal neurinoma, 3 cases of recurrent low grade cystic astrocytomas, and 1 case of craniopharyngioma). The Ommaya reservoir was installed stereotactically. The cyst volume and wall thickness were measured by MRI before Ho-166-chico injection. The thickness of the cyst wall is up to 4 mm. Ho-166-chico (555-740 MBq) injected into the cyst to result in 25 Gy of dose to a cyst wall at a depth of 4 mm. Dose to the cyst wall was estimated by Monte Carlo simulation using the EGS4 code. All Ho-166-chico injected was assumed to be uniformly distributed in the spherical cyst. After Ho-166-chico injection, the distribution of isotopes was monitored by gamma camera. Two injections were administrated in two cases, and one injection in all the others. The response was evaluated with MRI. Four of 7 cases were shrunk in size with thinning of the cyst wall, 2 of 7 cases showed growth arrest, and one case showed progression. Estimated surface dose of cyst wall was between 78 and 2566 Gy. No one showed systemic absorption of Ho-166-chico, and specific complication associated with isotope injection. Ho-166-chico intracavitary radiation therapy for cystic brain tumor may be safe, and reliable method and deserves further evaluation.

  14. Hyperoxia increases the uptake of 5-fluorouracil in mammary tumors independently of changes in interstitial fluid pressure and tumor stroma

    Directory of Open Access Journals (Sweden)

    Salvesen Gerd S

    2009-12-01

    Full Text Available Abstract Background Hypoxia is associated with increased resistance to chemo- and radiation-therapy. Hyperoxic treatment (hyperbaric oxygen has previously been shown to potentiate the effect of some forms of chemotherapy, and this has been ascribed to enhanced cytotoxicity or neovascularisation. The aim of this study was to elucidate whether hyperoxia also enhances any actual uptake of 5FU (5-fluorouracil into the tumor tissue and if this can be explained by changes in the interstitium and extracellular matrix. Methods One group of tumor bearing rats was exposed to repeated hyperbaric oxygen (HBO treatment (2 bar, pO2 = 2 bar, 4 exposures à 90 min, whereas one group was exposed to one single identical HBO treatment. Animals housed under normal atmosphere (1 bar, pO2 = 0.2 bar served as controls. Three doses of 5FU were tested for dose response. Uptake of [3H]-5FU in the tumor was assessed, with special reference to factors that might have contributed, such as interstitial fluid pressure (Pif, collagen content, oxygen stress (measured as malondialdehyd levels, lymphatics and transcapillary transport in the tumors. Results The uptake of the cytostatic agent increases immediately after a single HBO treatment (more than 50%, but not 24 hours after the last repeated HBO treatment. Thus, the uptake is most likely related to the transient increase in oxygenation in the tumor tissue. Factors like tumor Pif and collagen content, which decreased significantly in the tumor interstitium after repeated HBO treatment, was without effect on the drug uptake. Conclusion We showed that hyperoxia increases the uptake of [3H]-5FU in DMBA-induced mammary tumors per se, independently of changes in Pif, oxygen stress, collagen fibril density, or transendothelial transport alone. The mechanism by which such an uptake occur is still not elucidated, but it is clearly stimulated by elevated pO2.

  15. Photothermal therapy of melanoma tumor using multiwalled carbon nanotubes.

    Science.gov (United States)

    Sobhani, Zahra; Behnam, Mohammad Ali; Emami, Farzin; Dehghanian, Amirreza; Jamhiri, Iman

    2017-01-01

    Photothermal therapy (PTT) is a therapeutic method in which photon energy is transformed into heat rapidly via different operations to extirpate cancer. Nanoparticles, such as carbon nanotubes (CNTs) have exceptional optical absorbance in visible and near infrared spectra. Therefore, they could be a good converter to induce hyperthermia in PTT technique. In our study, for improving the dispersibility of multiwalled CNTs in water, the CNTs were oxidized (O-CNTs) and then polyethylene glycol (PEG) was used for wrapping the surface of nanotubes. The formation of a thin layer of PEG around the nanotubes was confirmed through Fourier transform infrared, thermogravimetric analysis, and field emission scanning electron microscopy techniques. Results of thermogravimetric analysis showed that the amount of PEG component in the O-CNT-PEG was approximately 80% (w/w). Cell cytotoxicity study showed that O-CNT was less cytotoxic than pristine multiwalled nanotubes, and O-CNT-PEG had the lowest toxicity against HeLa and HepG2 cell lines. The effect of O-CNT-PEG in reduction of melanoma tumor size after PTT was evaluated. Cancerous mice were exposed to a continuous-wave near infrared laser diode (λ=808 nm, P =2 W and I =8 W/cm 2 ) for 10 minutes once in the period of the treatment. The average size of tumor in mice receiving O-CNT-PEG decreased sharply in comparison with those that received laser therapy alone. Results of animal studies indicate that O-CNT-PEG is a powerful candidate for eradicating solid tumors in PTT technique.

  16. Viability of neutron brachytherapy technique using Cf252 for tumors of salivary glands therapy

    International Nuclear Information System (INIS)

    Andrade, Lidia M.; Campos, Tarcisio P.R.

    2000-01-01

    Gland salivary tumors, although uncommon, present significant characteristics such as distant metastasis, recurrence and average survive of five year for treated patients. Those tumors presents low response to a conventional radiotherapy, photon and electron therapy; thus, this modality is associated with surgery. Fast neutron therapy has been presented better results in controlling the local tumor in comparison with conventional radiotherapy. Brachytherapy with Cf-252 presents an alternative treatment for tumors. Those radiotherapy technique are discussed and analyzed. (author)

  17. Splenomegaly and tumor marker response following selective internal radiation therapy for non-resectable liver metastases from neuroendocrine tumor

    International Nuclear Information System (INIS)

    Shehata, M.; Yan, K.; Itoh, Seiji; King, J.; Glenn, D.; Quinn, R.; Morris, D.L.

    2009-01-01

    The aim of this study was to investigate changes in spleen size, the level of chromogranin A as a tumor marker, and the relationship between these two parameters before and 3 months after selective internal radiation therapy (SIRT) for non-resectable liver metastases from neuroendocrine tumor (NET). Our first serious adverse event with this relatively new treatment is also discussed. A retrospective review of a prospective database identified patients with non-resectable liver metastases from NET who underwent SIRT between 2003 and 2007. Patients who underwent CT scans before and 3 months after treatment were included. The patients were divided into two groups: those with and without a 20% or more increase in splenic volume on the CT scans. The percentages of patients showing a tumor marker response in the two groups were then compared. Fourteen patients were included in the present analysis. A tumor marker response was seen in 6 of 7 patients (85.7%) who showed an increase in splenic volume of >20%, and in 3 of 7 patients (42.9%) without an increase in splenic volume (p=0.266). There was one death as a result of oesophageal variceal bleeding due to portal hypertension at 9 months after treatment. Splenic enlargement after SIRT may be associated with tumor marker response, although this could not be confirmed statistically in this study due to the small number of patients. Long-term splenomegaly and portal hypertension may be important complications of SIRT. This issue needs to be investigated further using a larger number of patients and longer follow-up. (author)

  18. Improved apparatus for neutron capture therapy of rat brain tumors

    International Nuclear Information System (INIS)

    Liu, Hungyuan B.; Joel, D.D.; Slatkin, D.N.; Coderre, J.A.

    1994-01-01

    The assembly for irradiating tumors in the rat brain at the thermal neutron beam port of the Brookhaven Medical Research Reactor was redesigned to lower the average whole-body dose from different components of concomitant radiation without changing the thermal neutron fluence at the brain tumor. At present, the tumor-bearing rat is positioned in a rat holder that functions as a whole-body radiation shield. A 2.54 cm-thick collimator with a centered conical aperture, 6 cm diameter tapering to 2 cm diameter, is used to restrict the size of the thermal neutron field. Using the present holder and collimator as a baseline design, Monte Carlo calculations and mixed-field dosimetry were used to assess new designs. The computations indicate that a 0.5 cm-thick plate, made of 6 Li 2 CO 3 dispersed in polyethylene (Li-poly), instead of the existing rat holder, will reduce the whole-body radiation dose. Other computations show that a 10.16 cm-thick (4 inches) Li-poly collimator, having a centered conical aperture of 12 cm diameter tapering to 2 cm diameter, would further reduce the whole-body dose. The proposed irradiation apparatus of tumors in the rat brain, although requiring a 2.3-fold longer irradiation time, would reduce the average whole-body dose to less than half of that from the existing irradiation assembly. 7 refs., 4 figs., 7 tabs

  19. Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis.

    Science.gov (United States)

    Ali, Moustafa R K; Ibrahim, Ibrahim M; Ali, Hala R; Selim, Salah A; El-Sayed, Mostafa A

    Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment.

  20. Photothermal therapy of melanoma tumor using multiwalled carbon nanotubes

    Directory of Open Access Journals (Sweden)

    Sobhani Z

    2017-06-01

    Full Text Available Zahra Sobhani,1,2 Mohammad Ali Behnam,3 Farzin Emami,3 Amirreza Dehghanian,4 Iman Jamhiri5 1Quality Control Department, Faculty of Pharmacy, 2Center for Nanotechnology in Drug Delivery, Faculty of Pharmacy, Shiraz University of Medical Sciences, 3Opto-Electronic Research Center, Electrical and Electronics Engineering Department, Shiraz University of Technology, 4Pathology Department, 5Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Abstract: Photothermal therapy (PTT is a therapeutic method in which photon energy is transformed into heat rapidly via different operations to extirpate cancer. Nanoparticles, such as carbon nanotubes (CNTs have exceptional optical absorbance in visible and near infrared spectra. Therefore, they could be a good converter to induce hyperthermia in PTT technique. In our study, for improving the dispersibility of multiwalled CNTs in water, the CNTs were oxidized (O-CNTs and then polyethylene glycol (PEG was used for wrapping the surface of nanotubes. The formation of a thin layer of PEG around the nanotubes was confirmed through Fourier transform infrared, thermogravimetric analysis, and field emission scanning electron microscopy techniques. Results of thermogravimetric analysis showed that the amount of PEG component in the O-CNT-PEG was approximately 80% (w/w. Cell cytotoxicity study showed that O-CNT was less cytotoxic than pristine multiwalled nanotubes, and O-CNT-PEG had the lowest toxicity against HeLa and HepG2 cell lines. The effect of O-CNT-PEG in reduction of melanoma tumor size after PTT was evaluated. Cancerous mice were exposed to a continuous-wave near infrared laser diode (λ=808 nm, P=2 W and I=8 W/cm2 for 10 minutes once in the period of the treatment. The average size of tumor in mice receiving O-CNT-PEG decreased sharply in comparison with those that received laser therapy alone. Results of animal studies indicate that O-CNT-PEG is a powerful candidate for

  1. Real-time dose compensation methods for scanned ion beam therapy of moving tumors

    International Nuclear Information System (INIS)

    Luechtenborg, Robert

    2012-01-01

    Scanned ion beam therapy provides highly tumor-conformal treatments. So far, only tumors showing no considerable motion during therapy have been treated as tumor motion and dynamic beam delivery interfere, causing dose deteriorations. One proposed technique to mitigate these deteriorations is beam tracking (BT), which adapts the beam position to the moving tumor. Despite application of BT, dose deviations can occur in the case of non-translational motion. In this work, real-time dose compensation combined with beam tracking (RDBT) has been implemented into the control system to compensate these dose changes by adaptation of nominal particle numbers during irradiation. Compared to BT, significantly reduced dose deviations were measured using RDBT. Treatment planning studies for lung cancer patients including the increased biological effectiveness of ions revealed a significantly reduced over-dose level (3/5 patients) as well as significantly improved dose homogeneity (4/5 patients) for RDBT. Based on these findings, real-time dose compensated re-scanning (RDRS) has been proposed that potentially supersedes the technically complex fast energy adaptation necessary for BT and RDBT. Significantly improved conformity compared to re-scanning, i.e., averaging of dose deviations by repeated irradiation, was measured in film irradiations. Simulations comparing RDRS to BT revealed reduced under- and overdoses of the former method.

  2. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  3. Nano-aggregates: emerging delivery tools for tumor therapy.

    Science.gov (United States)

    Sharma, Vinod Kumar; Jain, Ankit; Soni, Vandana

    2013-01-01

    A plethora of formulation techniques have been reported in the literature for site-specific targeting of water-soluble and -insoluble anticancer drugs. Along with other vesicular and particulate carrier systems, nano-aggregates have recently emerged as a novel supramolecular colloidal carrier with promise for using poorly water-soluble drugs in molecular targeted therapies. Nano-aggregates possess some inherent properties such as size in the nanometers, high loading efficiency, and in vivo stability. Nano-aggregates can provide site-specific drug delivery via either a passive or active targeting mechanism. Nano-aggregates are formed from a polymer-drug conjugated amphiphilic block copolymer. They are suitable for encapsulation of poorly water-soluble drugs by covalent conjugation as well as physical encapsulation. Because of physical encapsulation, a maximum amount of drug can be loaded in nano-aggregates, which helps to achieve a sufficiently high drug concentration at the target site. Active transport can be achieved by conjugating a drug with vectors or ligands that bind specifically to receptors being overexpressed in the tumor cells. In this review, we explore synthesis and tumor targeting potential of nano-aggregates with active and passive mechanisms, and we discuss various characterization parameters, ex vivo studies, biodistribution studies, clinical trials, and patents.

  4. In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

    Science.gov (United States)

    Liu, Y H; Hawk, R M; Ramaprasad, S

    1995-01-01

    RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

  5. Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis

    Directory of Open Access Journals (Sweden)

    Ali MRK

    2016-09-01

    Full Text Available Moustafa R K Ali,1 Ibrahim M Ibrahim,2,† Hala R Ali,2,3 Salah A Selim,2 Mostafa A El-Sayed1,4 1School of Chemistry and Biochemistry, Georgia Institute of Technology, and Laser Dynamics Laboratory, Atlanta, GA, USA; 2Department of Veterinary Medicine, Cairo University, Giza, Cairo, Egypt; 3Department of Bacteriology and Immunology, Animal Health Research Institute (AHRI, Dokki, Giza, Egypt; 4School of Chemistry, King Abdul Aziz University, Jeddah, Saudi Arabia †Ibrahim M Ibrahim passed away on August 23, 2015 Abstract: Plasmonic photothermal therapy (PPTT is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment. Keywords: gold nanorods, natural mammary tumors, plasmonic photothermal therapy, canine, feline

  6. 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.

  7. The host immunological response to cancer therapy: An emerging concept in tumor biology

    International Nuclear Information System (INIS)

    Voloshin, Tali; Voest, Emile E.; Shaked, Yuval

    2013-01-01

    Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction—both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. -- Highlights: • Cancer therapy induces host molecular and cellular pro-tumorigenic effects. • Host effects in response to therapy may promote tumor relapse and metastasis. • The reactive host consists of immunological mediators promoting tumor re-growth. • Blocking therapy-induced host mediators may improve outcome

  8. The burden of chronic pain after major head and neck tumor therapy

    Directory of Open Access Journals (Sweden)

    Abdullah Sulieman Terkawi

    2017-01-01

    Conclusion: Our study highlighted the high burden of chronic pain after therapy for major head and neck tumors. We identified demographic and clinical factors that are associated with the presence of chronic pain. Further studies are required to better understand the risk factors to implement strategies to prevent, alleviate, and treat chronic pain associated with major head and neck tumor therapies.

  9. The host immunological response to cancer therapy: An emerging concept in tumor biology

    Energy Technology Data Exchange (ETDEWEB)

    Voloshin, Tali [Department of Molecular Pharmacology, Rappaport Faculty of Medicine and the Rappaport Institute, Technion—Israel Institute of Technology, 1 Efron Street, Bat Galim, Haifa 31096 (Israel); Voest, Emile E. [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Shaked, Yuval, E-mail: yshaked@tx.technion.ac.il [Department of Molecular Pharmacology, Rappaport Faculty of Medicine and the Rappaport Institute, Technion—Israel Institute of Technology, 1 Efron Street, Bat Galim, Haifa 31096 (Israel)

    2013-07-01

    Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction—both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. -- Highlights: • Cancer therapy induces host molecular and cellular pro-tumorigenic effects. • Host effects in response to therapy may promote tumor relapse and metastasis. • The reactive host consists of immunological mediators promoting tumor re-growth. • Blocking therapy-induced host mediators may improve outcome.

  10. Predicting oropharyngeal tumor volume throughout the course of radiation therapy from pretreatment computed tomography data using general linear models.

    Science.gov (United States)

    Yock, Adam D; Rao, Arvind; Dong, Lei; Beadle, Beth M; Garden, Adam S; Kudchadker, Rajat J; Court, Laurence E

    2014-05-01

    The purpose of this work was to develop and evaluate the accuracy of several predictive models of variation in tumor volume throughout the course of radiation therapy. Nineteen patients with oropharyngeal cancers were imaged daily with CT-on-rails for image-guided alignment per an institutional protocol. The daily volumes of 35 tumors in these 19 patients were determined and used to generate (1) a linear model in which tumor volume changed at a constant rate, (2) a general linear model that utilized the power fit relationship between the daily and initial tumor volumes, and (3) a functional general linear model that identified and exploited the primary modes of variation between time series describing the changing tumor volumes. Primary and nodal tumor volumes were examined separately. The accuracy of these models in predicting daily tumor volumes were compared with those of static and linear reference models using leave-one-out cross-validation. In predicting the daily volume of primary tumors, the general linear model and the functional general linear model were more accurate than the static reference model by 9.9% (range: -11.6%-23.8%) and 14.6% (range: -7.3%-27.5%), respectively, and were more accurate than the linear reference model by 14.2% (range: -6.8%-40.3%) and 13.1% (range: -1.5%-52.5%), respectively. In predicting the daily volume of nodal tumors, only the 14.4% (range: -11.1%-20.5%) improvement in accuracy of the functional general linear model compared to the static reference model was statistically significant. A general linear model and a functional general linear model trained on data from a small population of patients can predict the primary tumor volume throughout the course of radiation therapy with greater accuracy than standard reference models. These more accurate models may increase the prognostic value of information about the tumor garnered from pretreatment computed tomography images and facilitate improved treatment management.

  11. HER2-Targeted Polyinosine/Polycytosine Therapy Inhibits Tumor Growth and Modulates the Tumor Immune Microenvironment.

    Science.gov (United States)

    Zigler, Maya; Shir, Alexei; Joubran, Salim; Sagalov, Anna; Klein, Shoshana; Edinger, Nufar; Lau, Jeffrey; Yu, Shang-Fan; Mizraji, Gabriel; Globerson Levin, Anat; Sliwkowski, Mark X; Levitzki, Alexander

    2016-08-01

    The development of targeted therapies that affect multiple signaling pathways and stimulate antitumor immunity is greatly needed. About 20% of patients with breast cancer overexpress HER2. Small molecules and antibodies targeting HER2 convey some survival benefits; however, patients with advanced disease succumb to the disease under these treatment regimens, possibly because HER2 is not completely necessary for the survival of the targeted cancer cells. In the present study, we show that a polyinosine/polycytosine (pIC) HER2-homing chemical vector induced the demise of HER2-overexpressing breast cancer cells, including trastuzumab-resistant cells. Targeting pIC to the tumor evoked a number of cell-killing mechanisms, as well as strong bystander effects. These bystander mechanisms included type I IFN induction, immune cell recruitment, and activation. The HER2-targeted pIC strongly inhibited the growth of HER2-overexpressing tumors in immunocompetent mice. The data presented here could open additional avenues in the treatment of HER2-positive breast cancer. Cancer Immunol Res; 4(8); 688-97. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. Recommendations for diagnostics and therapy of gastrointestinal stromal tumors (GIST) in 2010

    International Nuclear Information System (INIS)

    Rutkowski, P.; Kulig, J.; Osuch, C.

    2011-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Over the last years advances in the understanding of the molecular mechanisms of GIST pathogenesis have resulted in the emerging of GIST as a distinct sarcoma entity. This paper presents the guidelines for diagnostics and therapy of these tumors based on scientific research and experts' experience, These guidelines are commonly accepted and worthy of recommendation. Overexpression of the KIT receptor, as a consequence of mutation of the KIT protooncogene is highly specific for GIST and enables immunohistochemical detection staining (CD117) in tumor specimens. It is the most important criterion in microscopic diagnostics and for indicating treatment with small-molecule tyrosine kinase inhibitors. Sending material for molecular analysis is strongly recommended (for KIT and PDGFRA genotyping). Radical surgery is still the mainstay treatment for primary, localized, resectable GISTs, although although a significant ratio of patients after potentially curative operations develop recurrent or metastatic disease. In inoperable/metastatic lesions the treatment of choice is a tyrosine kinase inhibitor - imatynib mesylate - the first effective systemic therapy in advanced CD117(+) GIST. The recommended initial dose should be 400 mg daily (800 mg for exon 9 KIT mutants). Treatment monitoring should be based on serial computed tomography imaging of the abdominal cavity with the assessment of changes of tumor size and density. In case of disease progression the increase of imatynib dose to 800 mg daily is recommended and - if progression maintains - sunitinib in the initial dose of 50 mg daily should be introduced. Clinical trials evaluating the role of surgery combined with imatynib and the efficacy of other molecular targeted drugs in resistant cases are ongoing. Existing data indicate the beneficial role of adjuvant imatynib therapy in terms of relapse-free survival

  13. Changing Histopathological Diagnostics by Genome-Based Tumor Classification

    Directory of Open Access Journals (Sweden)

    Michael Kloth

    2014-05-01

    Full Text Available Traditionally, tumors are classified by histopathological criteria, i.e., based on their specific morphological appearances. Consequently, current therapeutic decisions in oncology are strongly influenced by histology rather than underlying molecular or genomic aberrations. The increase of information on molecular changes however, enabled by the Human Genome Project and the International Cancer Genome Consortium as well as the manifold advances in molecular biology and high-throughput sequencing techniques, inaugurated the integration of genomic information into disease classification. Furthermore, in some cases it became evident that former classifications needed major revision and adaption. Such adaptations are often required by understanding the pathogenesis of a disease from a specific molecular alteration, using this molecular driver for targeted and highly effective therapies. Altogether, reclassifications should lead to higher information content of the underlying diagnoses, reflecting their molecular pathogenesis and resulting in optimized and individual therapeutic decisions. The objective of this article is to summarize some particularly important examples of genome-based classification approaches and associated therapeutic concepts. In addition to reviewing disease specific markers, we focus on potentially therapeutic or predictive markers and the relevance of molecular diagnostics in disease monitoring.

  14. The role of radiation therapy in the management of desmoid tumors

    International Nuclear Information System (INIS)

    Schulz-Ertner, D.; Zierhut, D.; Mende, U.; Harms, W.; Branitzki, P.; Wannenmacher, M.

    2002-01-01

    Purpose: To investigate the role of radiation therapy (RT) in the management of desmoid tumors. Patients and Methods: Retrospective analysis was performed on 28 patients with desmoid tumors treated with radiation therapy between March 1989 and March 1999. Tumor site was intraabdominal in three, abdominal wall in three and extraabdominal in 22 patients. Median tumor dose was 48 Gy (range 36-60 Gy). Radiation therapy was delivered postoperatively in 26 of 28 patients, two patients received radiation therapy for unresectable recurrent tumors. Results: Median follow-up was 46 months (range 13-108 months). Actuarial 5-year control rate was 73%. We observed six recurrences, located within the radiation field in one patient, out of field in two and at the field margin in three patients. All patients with intraabdominal tumors have been controlled without severe side effects. Conclusions: Radiation therapy is an effective treatment after incomplete resection of desmoid tumors. We did not observe a benefit for tumor doses exceeding 50 Gy. In some patients with circumscribed intraabdominal desmoid tumors, radiation therapy might be a treatment option with low toxicity, if 3-D treatment planning is utilized. (orig.) [de

  15. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ruth S Waterman

    Full Text Available Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2.Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation.These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

  16. Change in Seroma Volume During Whole-Breast Radiation Therapy

    International Nuclear Information System (INIS)

    Sharma, Rajiv; Spierer, Marnee; Mutyala, Subhakar; Thawani, Nitika; Cohen, Hillel W.; Hong, Linda; Garg, Madhur K.; Kalnicki, Shalom

    2009-01-01

    Purpose: After breast-conserving surgery, a seroma often forms in the surgical cavity. If not drained, it may affect the volume of tumor bed requiring a boost after whole-breast radiation therapy (WBRT). Our objective was to evaluate the change in seroma volume that occurs during WBRT, before boost planning. Methods and Materials: A retrospective review was performed of women receiving breast-conserving therapy with evidence of seroma at the time of WBRT planning. Computed tomography (CT) simulation was performed before WBRT and before the tumor bed boost. All patients received either a hypofractionated (42.4 Gy/16 fraction + 9.6 Gy/4 fraction boost) or standard fractionated (50.4 Gy/28 fraction + 10 Gy/5 fraction boost) regimen. Seroma volumes were contoured and compared on CT at the time of WBRT simulation and tumor bed boost planning. Results: Twenty-four patients with evidence of seroma were identified and all patients received WBRT without drainage of the seroma. Mean seroma volume before WBRT and at boost planning were significantly different at 65.7 cm 3 (SD, 50.5 cm 3 ) and 35.6 cm 3 (SD, 24.8 cm 3 ), respectively (p < 0.001). Mean and median reduction in seroma volume during radiation were 39.6% (SD, 23.8%) and 46.2% (range, 10.7-76.7%), respectively. Fractionation schedule was not correlated with change in seroma volume. Length of time from surgery to start of radiation therapy showed an inverse correlation with change in seroma volume (Pearson correlation r = -0.53, p < 0.01). Conclusions: The volume of seroma changes significantly during WBRT. Consequently, the accuracy of breast boost planning is likely affected, as is the volume of normal breast tissue irradiated. CT-based boost planning before boost irradiation is suggested to ensure appropriate coverage.

  17. Expression of complement and pentraxin proteins in acute phase response elicited by tumor photodynamic therapy: the engagement of adrenal hormones.

    Science.gov (United States)

    Merchant, Soroush; Huang, Naiyan; Korbelik, Mladen

    2010-12-01

    Treatment of solid tumors by photodynamic therapy (PDT) was recently shown to trigger a strong acute phase response. Using the mouse Lewis lung carcinoma (LLC) model, the present study examined complement and pentraxin proteins as PDT-induced acute phase reactants. The results show a distinct pattern of changes in the expression of genes encoding these proteins in the tumor, as well as host liver and spleen, following PDT mediated by photosensitizer Photofrin™. These changes were influenced by glucocorticoid hormones, as evidenced by transcriptional activation of glucocorticoid receptor and the upregulation of gene encoding this receptor. The expression of gene for glucocorticoid-induced zipper (GILZ) protein, whose activity is particularly susceptible to glucocorticoid regulation, was also changed in PDT-treated tumors. A direct demonstration that tumor PDT induces glucocorticoid hormone upregulation is provided by documenting elevated levels of serum corticosterone in mice bearing PDT-treated LLC tumors. Tumor response to PDT was negatively affected by blocking glucocorticoid receptor activity, which suggests that glucocorticoid hormones have a positive impact on the therapeutic outcome with this therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy.

    Science.gov (United States)

    Zhang, Bo; Shi, Wei; Jiang, Ting; Wang, Lanting; Mei, Heng; Lu, Heng; Hu, Yu; Pang, Zhiqing

    2016-09-20

    Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment.

  19. Acceptable Toxicity After Stereotactic Body Radiation Therapy for Liver Tumors Adjacent to the Central Biliary System

    Energy Technology Data Exchange (ETDEWEB)

    Eriguchi, Takahisa; Takeda, Atsuya; Sanuki, Naoko; Oku, Yohei; Aoki, Yousuke [Radiation Oncology Center, Ofuna Chuo Hospital, Kanagawa (Japan); Shigematsu, Naoyuki [Department of Radiology, Keio University School of Medicine, Tokyo (Japan); Kunieda, Etsuo, E-mail: kunieda-mi@umin.ac.jp [Department of Radiation Oncology, Tokai University, Kanagawa (Japan)

    2013-03-15

    Purpose: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors. Methods and Materials: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ. Results: Fifty patients with 55 tumors were irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient. Conclusions: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity.

  20. Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies

    Science.gov (United States)

    Privalov, Valeriy A.; Lappa, Alexander V.; Bigbov, Elmir N.

    2011-02-01

    A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer RadachlorineTM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm2. Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

  1. Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after 177Lu[Lu]-octreotate therapy.

    Science.gov (United States)

    Spetz, Johan; Rudqvist, Nils; Langen, Britta; Parris, Toshima Z; Dalmo, Johanna; Schüler, Emil; Wängberg, Bo; Nilsson, Ola; Helou, Khalil; Forssell-Aronsson, Eva

    2018-05-01

    Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with 177 Lu[Lu]-octreotate. Despite being highly effective in animal models, 177 Lu[Lu]-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for 177 Lu[Lu]-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq 177 Lu[Lu]-octreotate (non-curative amount) or mock-treated with saline solution. Animals were killed 1, 3, 7 or 41 d after injection. Total RNA was extracted from the tumor samples and profiled using Illumina microarray expression analysis. Differentially expressed genes were identified (treated vs. control) and pathway analysis was performed. Distribution of differentially expressed transcripts indicated a time-dependent treatment response in GOT1 tumors after 177 Lu[Lu]-octreotate administration. Regulation of CDKN1A, BCAT1 and PAM at 1 d after injection was compatible with growth arrest as the initial response to treatment. Upregulation of APOE and BAX at 3 d, and ADORA2A, BNIP3, BNIP3L and HSPB1 at 41 d after injection suggests first activation and then inhibition of the intrinsic apoptotic pathway during tumor regression and regrowth, respectively. Transcriptional analysis showed radiation-induced apoptosis as an early response after 177 Lu[Lu]-octreotate administration, followed by pro-survival transcriptional changes in the tumor during the regrowth phase. Time-dependent changes in cell cycle and apoptosis-related processes suggest different time points after radionuclide therapy when tumor cells may be more susceptible to additional treatment, highlighting the importance of timing when administering multiple therapeutic agents. Copyright © 2018 The Authors. Published by Elsevier Inc. All

  2. Anti-tumor effects of Egr-IFN γ gene therapy combined with 125I-UdR radionuclide therapy

    International Nuclear Information System (INIS)

    Zhao Jingguo; Ni Yanjun; Song Xiangfu; Li Yanyi; Yang Wei; Sun Ting; Ma Qingjie; Gao Fengtong

    2008-01-01

    Objective: To explore the anti-tumor effects of Egr-IFNγ gene therapy combined with 125 I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNγ mixed with liposome was injected into tumor. 48 h later, 370 kBq 125 I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNγ in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNγ + 125 I-UdR group were obviously lower than those of control group, 125 I-UdR group and pcDNAEgr-1 + 125 I-UdR group 6-15 d after gene-radionuclide therapy. IFNγ protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNγ + 125 I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNγ + 125 I-UdR group was significantly higher than that in the other groups (P 125 I-UdR radionuclide therapy are better than those of 125 I-UdR therapy. (authors)

  3. Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Huamani, Jessica; Fu, Allie; Hallahan, Dennis E.

    2006-01-01

    The tumor microenvironment, in particular, the tumor vasculature, as an important target for the cytotoxic effects of radiation therapy is an established paradigm for cancer therapy. We review the evidence that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated in endothelial cells exposed to ionizing radiation (IR) and is a molecular target for the development of novel radiation sensitizing agents. On the basis of this premise, several promising preclinical studies that targeted the inhibition of the PI3K/Akt activation as a potential method of sensitizing the tumor vasculature to the cytotoxic effects of IR have been conducted. An innovative strategy to guide cytotoxic therapy in tumors treated with radiation and PI3K/Akt inhibitors is presented. The evidence supports a need for further investigation of combined-modality therapy that involves radiation therapy and inhibitors of PI3K/Akt pathway as a promising strategy for improving the treatment of patients with cancer

  4. Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

    Directory of Open Access Journals (Sweden)

    Soo Khee

    2009-11-01

    Full Text Available Abstract Background Photodynamic therapy (PDT is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR, on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period. Results Our results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux. Conclusion The combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors.

  5. Density overwrites of internal tumor volumes in intensity modulated proton therapy plans for mobile lung tumors

    Science.gov (United States)

    Botas, Pablo; Grassberger, Clemens; Sharp, Gregory; Paganetti, Harald

    2018-02-01

    The purpose of this study was to investigate internal tumor volume density overwrite strategies to minimize intensity modulated proton therapy (IMPT) plan degradation of mobile lung tumors. Four planning paradigms were compared for nine lung cancer patients. Internal gross tumor volume (IGTV) and internal clinical target volume (ICTV) structures were defined encompassing their respective volumes in every 4DCT phase. The paradigms use different planning CT (pCT) created from the average intensity projection (AIP) of the 4DCT, overwriting the density within the IGTV to account for movement. The density overwrites were: (a) constant filling with 100 HU (C100) or (b) 50 HU (C50), (c) maximum intensity projection (MIP) across phases, and (d) water equivalent path length (WEPL) consideration from beam’s-eye-view. Plans were created optimizing dose-influence matrices calculated with fast GPU Monte Carlo (MC) simulations in each pCT. Plans were evaluated with MC on the 4DCTs using a model of the beam delivery time structure. Dose accumulation was performed using deformable image registration. Interplay effect was addressed applying 10 times rescanning. Significantly less DVH metrics degradation occurred when using MIP and WEPL approaches. Target coverage (D99≥slant 70 Gy(RBE)) was fulfilled in most cases with MIP and WEPL (D{{99}WEPL}=69.2+/- 4.0 Gy (RBE)), keeping dose heterogeneity low (D5-D{{95}WEPL}=3.9+/- 2.0 Gy(RBE)). The mean lung dose was kept lowest by the WEPL strategy, as well as the maximum dose to organs at risk (OARs). The impact on dose levels in the heart, spinal cord and esophagus were patient specific. Overall, the WEPL strategy gives the best performance and should be preferred when using a 3D static geometry for lung cancer IMPT treatment planning. Newly available fast MC methods make it possible to handle long simulations based on 4D data sets to perform studies with high accuracy and efficiency, even prior to individual treatment planning.

  6. Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

    Science.gov (United States)

    Cheng, Yu; Morshed, Ramin; Auffinger, Brenda; Tobias, Alex L.; Lesniak, Maciej S.

    2013-01-01

    Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management. PMID:24060923

  7. Cranial nerves - spectrum of inflammatory and tumorous changes

    International Nuclear Information System (INIS)

    Nemec, S.F.; Kasprian, G.; Nemec, U.; Czerny, C.

    2009-01-01

    Inflammatory processes as well as primary and secondary tumorous changes may involve cranial nerves causing neurological deficits. In addition to neurologists, ENT physicians, ophthalmologists and maxillofacial surgeons, radiologists play an important role in the investigation of patients with cranial nerve symptoms. Multidetector computed tomography (MDCT) and particularly magnetic resonance imaging (MRI) allow the depiction of the cranial nerve anatomy and pathological neural changes. This article briefly describes the imaging techniques in MDCT and MRI and is dedicated to the radiological presentation of inflammatory and tumorous cranial nerve pathologies. (orig.) [de

  8. The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

    International Nuclear Information System (INIS)

    Mao Jingfang; Kocak, Zafer; Zhou Sumin; Garst, Jennifer; Evans, Elizabeth S.; Zhang Junan; Larrier, Nicole A.; Hollis, Donna R.; Folz, Rodney J.; Marks, Lawrence B.

    2007-01-01

    Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction

  9. Changes in T-cell subsets after radiation therapy

    International Nuclear Information System (INIS)

    Yang, S.J.; Rafla, S.; Youssef, E.; Selim, H.; Salloum, N.; Chuang, J.Y.

    1988-01-01

    The T-cell subsets of 129 patients with cancer were counted before and after radiation therapy. The cells were labeled with monoclonal antibodies that were specific for each type of T cell. Significant changes after therapy were decreases in the proportion of T-helper/inducer cells, pan-T cells, and in the ratio of T-helper/inducer to T-suppressor/cytotoxic cells. There was an increase in the percentage of T-suppressor/cytotoxic cells. When the site of the primary cancer was considered, genitourinary cancer and cancer of the head and neck both showed a decreased percentage of T-helper/inducer cells and a reduced ratio of T-helper/inducer to T-suppressor/cytotoxic cells. The percentage of pan-T cells in head and neck cancer and the ratio of T-helper/inducer to T-suppressor/cytotoxic cells in breast cancer were decreased. The percentage of T-helper cells was particularly decreased by radiation therapy in advanced stages of cancer, in higher grade tumors, and in larger tumors. The absolute numbers of various T-cell subsets were decreased in all groups

  10. Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

    OpenAIRE

    Baay, Marc; Brouwer, Anja; Pauwels, Patrick; Peeters, Marc; Lardon, Filip

    2011-01-01

    Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages pro...

  11. Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship

    NARCIS (Netherlands)

    Netea-Maier, R.T.; Smit, J.W.A.; Netea, M.G.

    2018-01-01

    In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production

  12. Mechanisms of Change in Interpersonal Therapy (IPT)

    OpenAIRE

    Lipsitz, Joshua D.; Markowitz, John C.

    2013-01-01

    Although interpersonal therapy (IPT) has demonstrated efficacy for mood and other disorders, little is known about how IPT works. We present interpersonal change mechanisms that we hypothesize account for symptom change in IPT. IPT’s interpersonal model integrates both relational theory, building on work by Sullivan, Bowlby, and others, and insights based on research findings regarding stress, social support, and illness to highlight contextual factors thought to precipitate and maintain psyc...

  13. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2017-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

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

    Science.gov (United States)

    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.

  15. Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

    Directory of Open Access Journals (Sweden)

    Thorsten Frenzel

    Full Text Available Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior.Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

  16. Present status of fast neutron therapy for the malignant tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tsunemoto, H; Morita, S; Honke, Y [National Inst. of Radiological Sciences, Chiba (Japan)

    1980-04-01

    Fast neutron therapy has been applied to the treatment of cancer of the head and the neck, prostatic cancer, osteosarcoma, and malignant melanoma, and the basic treatment schedule for this therapy for them has been almost established. The effectiveness of this therapy for squamous cell carcinoma of the uterus will be established by the results of future clinical application of this therapy. It is expected that postoperative irradiation of fast neutron will decrease local recurrence of adenocarcinoma of the uterus. Treatment schedule for fast neutron therapy for esophageal cancer and lung cancer must be established, and moreover, it is necessary to apply this therapy to the treatment of gastric and pancreatic cancer.

  17. Tumor response parameters for head and neck cancer derived from tumor-volume variation during radiation therapy

    International Nuclear Information System (INIS)

    Chvetsov, Alexei V.

    2013-01-01

    Purpose: The main goal of this paper is to reconstruct a distribution of cell survival fractions from tumor-volume variation for a heterogeneous group of head and neck cancer patients and compare this distribution to the data from predictive assays. Methods: To characterize the tumor-volume variation during radiation therapy treatment, the authors use a two-level tumor-volume model of cell population that separates the entire tumor cell population into two subpopulations of viable cells and lethally damaged cells. This parameterized radiobiological model is integrated with a least squares objective function and a simulated annealing optimization algorithm to describe time-dependent tumor-volume variation rates in individual patients. Several constraints have been used in the optimization problem because tumor-volume variation during radiotherapy is described by a sum of exponentials; therefore, the problem of accurately fitting a model to measured data is ill-posed. The model was applied to measured tumor-volume variation curves from a clinical study on tumor-volume variation during radiotherapy for 14 head and neck cancer patients in which an integrated CT/linear particle accelerator (LINAC) system was used for tumor-volume measurements. Results: The two-level cell population tumor-volume modeling is capable of describing tumor-volume variation throughout the entire treatment for 11 of the 14 patients. For three patients, the tumor-volume variation was described only during the initial part of treatment, a fact that may be related to the neglected hypoxia in the two-level approximation. The predicted probability density distribution for the survival fractions agrees with the data obtained using in vitro studies with predictive assays. The mean value 0.35 of survival fraction obtained in this study is larger than the value 0.32 from in vitro studies, which could be expected because of greater repair in vivo. The mean half-life obtained in this study for the head

  18. Chemotherapy-Induced Macrophage Infiltration into Tumors Enhances Nanographene-Based Photodynamic Therapy.

    Science.gov (United States)

    Zhao, Yang; Zhang, Chenran; Gao, Liquan; Yu, Xinhe; Lai, Jianhao; Lu, Dehua; Bao, Rui; Wang, Yanpu; Jia, Bing; Wang, Fan; Liu, Zhaofei

    2017-11-01

    Increased recruitment of tumor-associated macrophages (TAM) to tumors following chemotherapy promotes tumor resistance and recurrence and correlates with poor prognosis. TAM depletion suppresses tumor growth, but is not highly effective due to the effects of tumorigenic mediators from other stromal sources. Here, we report that adoptive macrophage transfer led to a dramatically enhanced photodynamic therapy (PDT) effect of 2-(1-hexyloxyethyl)-2-devinyl pyropheophor-bide-alpha (HPPH)-coated polyethylene glycosylated nanographene oxide [GO(HPPH)-PEG] by increasing its tumor accumulation. Moreover, tumor treatment with commonly used chemotherapeutic drugs induced an increase in macrophage infiltration into tumors, which also enhanced tumor uptake and the PDT effects of GO(HPPH)-PEG, resulting in tumor eradication. Macrophage recruitment to tumors after chemotherapy was visualized noninvasively by near-infrared fluorescence and single-photon emission CT imaging using F4/80-specific imaging probes. Our results demonstrate that chemotherapy combined with GO(HPPH)-PEG PDT is a promising strategy for the treatment of tumors, especially those resistant to chemotherapy. Furthermore, TAM-targeted molecular imaging could potentially be used to predict the efficacy of combination therapy and select patients who would most benefit from this treatment approach. Cancer Res; 77(21); 6021-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies

    Science.gov (United States)

    Kohandel, M.; Kardar, M.; Milosevic, M.; Sivaloganathan, S.

    2007-07-01

    Tumors cannot grow beyond a certain size (about 1-2 mm in diameter) through simple diffusion of oxygen and other essential nutrients into the tumor. Angiogenesis, the formation of blood vessels from pre-existing vessels, is a crucial and observed step, through which a tumor obtains its own blood supply. Thus, strategies that interfere with the development of this tumor vasculature, known as anti-angiogenic therapy, represent a novel approach to controlling tumor growth. Several pre-clinical studies have suggested that currently available angiogenesis inhibitors are unlikely to yield significant sustained improvements in tumor control on their own, but rather will need to be used in combination with conventional treatments to achieve maximal benefit. Optimal sequencing of anti-angiogenic treatment and radiotherapy or chemotherapy is essential to the success of these combined treatment strategies. Hence, a major challenge to mathematical modeling and computer simulations is to find appropriate dosages, schedules and sequencing of combination therapies to control or eliminate tumor growth. Here, we present a mathematical model that incorporates tumor cells and the vascular network, as well as their interplay. We can then include the effects of two different treatments, conventional cytotoxic therapy and anti-angiogenic therapy. The results are compared with available experimental and clinical data.

  20. Anticonvulsant therapy in brain-tumor related epilepsy

    Directory of Open Access Journals (Sweden)

    Fröscher Walter

    2016-06-01

    Full Text Available Background. The lifetime risk of patients with brain tumors to have focal epileptic seizures is 10-100%; the risk depends on different histology. Specific guidelines for drug treatment of brain tumor-related seizures have not yet been established.

  1. Modeling tumor-associated edema in gliomas during anti-angiogenic therapy and its impact on imageable tumor

    Directory of Open Access Journals (Sweden)

    Andrea eHawkins-Daarud

    2013-04-01

    Full Text Available Glioblastoma, the most aggressive form of primary brain tumor is predominantly assessed with gadolinium-enhanced T1-weighted (T1Gd and T2-weighted magnetic resonance imaging (MRI. Pixel intensity enhancement on the T1Gd image is understood to correspond to the gadolinium contrast agent leaking from the tumor-induced neovasculature, while hyperintensity on the T2/FLAIR images corresponds with edema and infiltrated tumor cells. None of these modalities directly show tumor cells; rather, they capture abnormalities in the microenvironment caused by the presence of tumor cells. Thus, assessing disease response after treatments impacting the microenvironment remains challenging through the obscuring lens of MR imaging. Anti-angiogenic therapies have been used in the treatment of gliomas with spurious results ranging from no apparent response to significant imaging improvement with the potential for extremely diffuse patterns of tumor recurrence on imaging and autopsy. Anti-angiogenic treatment normalizes the vasculature, effectively decreasing vessel permeability and thus reducing tumor-induced edema, drastically altering T2-weighted MRI. We extend a previously developed mathematical model of glioma growth to explicitly incorporate edema formation allowing us to directly characterize and potentially predict the effects of anti-angiogenics on imageable tumor growth. A comparison of simulated glioma growth and imaging enhancement with and without bevacizumab supports the current understanding that anti-angiogenic treatment can serve as a surrogate for steroids and the clinically-driven hypothesis that anti-angiogenic treatment may not have any significant effect on the growth dynamics of the overall tumor-cell populations. However, the simulations do illustrate a potentially large impact on the level of edematous extracellular fluid, and thus on what would be imageable on T2/FLAIR MR for tumors with lower proliferation rates.

  2. Proton therapy for pediatric cranial tumors: preliminary report on treatment and disease-related morbidities

    International Nuclear Information System (INIS)

    McAllister, Bruce; Archambeau, John O.; Nguyen, M. Connie; Slater, Jerry D.; Loredo, Lilia; Schulte, Reinhard; Alvarez, Ofelia; Bedros, Antranik A.; Kaleita, Thomas; Moyers, Michael; Miller, Daniel; Slater, James M.

    1997-01-01

    Purpose: Accelerated protons were used in an attempt to limit treatment-related morbidity in children with tumors in or near the developing brain, by reducing the integral dose to adjacent normal tissues. Methods and Materials: Children treated with protons at Loma Linda University Medical Center between August 1991 and December 1994 were analyzed retrospectively. Twenty-eight children, aged 1 to 18 years, were identified as at risk for brain injury from treatment. Medical records, physical examinations, and correspondence with patients, their parents, and referring physicians were analyzed. The investigators tabulated post-treatment changes in pre-treatment signs and symptoms and made judgments as to whether improvement, no change, or worsening related to disease or treatment had supervened. Magnetic resonance images were correlated with clinical findings and radiographic impressions were tabulated. Results: Follow-up ranged from 7 to 49 months (median 25 months). Four instances of treatment-related morbidity were identified. Forty-one instances of site-specific, disease-related morbidity were identified: 15 improved or resolved and 26 remained unchanged after treatment. Four patients had radiographic evidence of local failure. Three of these patients, including two with high-grade glioma, have died. Conclusion: Early treatment-related morbidity associated with proton therapy is low. Tumor progression remains a problem when treating certain histologies such as high-grade glioma. Escalating the dose delivered to target volumes may benefit children with tumors associated with poor rates of local control. Long-term follow-up, including neurocognitive testing, is in progress to assess integral-dose effects on cognitive, behavioral and developmental outcomes in children with cranial tumors

  3. Echosonography and surgical therapy of facial skin tumors

    Directory of Open Access Journals (Sweden)

    Pešić Zoran U.

    2002-01-01

    Full Text Available In the second half of the 20 century, echosonography has been used in many medical specialties. In 1992 and 1993 highfrequencies echosonography was used in the examination of irritant and allergic skin lesions in order to examine the effects of different therapeuthical agents on the skin lesions [1-4]. Hoffmann used highfrequencies echosonography in the examination of healing of skin lesions [3]. By their incidence skin tumors are the largest group of newly discovered tumors, and their usual location is on the face [5-7]. By clinical examination it is not possible to precisely determine the depth of tumor border; therefore, the radically performed surgical excision is the only correct surgical treatment. The aim of this study was to estimate the results of preoperatively performed high frequencies echosonography in order to reduce the number of incorrectly performed surgical excisions of skin tumors. The group was composed of 40 patients with 45 tumors, who first underwent echosonographic diagnostic procedure (20 MHz, Hadsund electronic, Hadsund Technology, Denmark and then surgical excision; patients in control group (45 patients with 45 tumors were only subjected to surgical excision. Excised tumors were then pathohistologically analyzed, and measurements of tumor depth progression were performed. Margins of pathohistological specimen were controlled for the presence of tumor cells. Results of measurements of tumor depth obtained by echosonography and pathohistological measurements were compared. By Jate's modification of c2 test results regarding correct and incorrect surgical excision in patients and control group were compared. By linear regression analysis results of tumor depth obtained by echosonographic and pathohistologic examinations were compared. Hypoechogen zone echosonographic results were used like criteria for tumor expansion. Results of tumor depth measurements are presented in Table 1. Linear regression analysis showed (R = 0

  4. Clinical implications of heterogeneity of tumor response to radiation therapy

    International Nuclear Information System (INIS)

    Suit, H.; Skates, S.; Taghian, A.; Okunieff, P.; Efird, J.T.

    1992-01-01

    Heterogeneity of response of tumor tissue to radiation clearly exists. Major parameters include histopathologic type, size (number of tumor rescue units (TRUs)), hemoglobin concentration, cell proliferation kinetics and immune rejection reaction by host. Further, normal and presumably tumor tissue response is altered in certain genetic diseases, e.g. ataxia telangiectasia. Any assessment of response of tumor tissue to a new treatment method or the testing of a new clinical response predictor is optimally based upon a narrow strata, viz., uniform with respect to known parameters of response, e.g. size, histological type. Even among tumors of such a clinical defined narrow strata, there will be residual heterogeneity with respect to inherent cellular radiation sensitivity, distributions of pO 2 , (SH), cell proliferation, etc. (author). 39 refs., 7 figs., 3 tabs

  5. Octreotide Is Ineffective in Treating Tumor-Induced Osteomalacia: Results of a Short-Term Therapy.

    Science.gov (United States)

    Ovejero, Diana; El-Maouche, Diala; Brillante, Beth A; Khosravi, Azar; Gafni, Rachel I; Collins, Michael T

    2017-08-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which unregulated hypersecretion of fibroblast growth factor 23 (FGF23) by phosphaturic mesenchymal tumors (PMT) causes renal phosphate wasting, hypophosphatemia, and osteomalacia. The resulting mineral homeostasis abnormalities and skeletal manifestations can be reversed with surgical resection of the tumor. Unfortunately, PMTs are often difficult to locate, and medical treatment with oral phosphate and vitamin D analogues is either insufficient to manage the disease or not tolerated. Octreotide has been proposed as a potential treatment for TIO due to the presence of somatostatin receptors (SSTR) on PMTs; however, the role of somatostatin signaling in PMTs and the efficacy of treatment of TIOs with somatostatin analogues is not clear. In an effort to evaluate the efficacy of octreotide therapy in TIO, five subjects with TIO were treated with octreotide for 3 days. Blood intact FGF23, phosphate, and 1,25(OH) 2 D 3 , and tubular reabsorption of phosphate (TRP) were measured at frequent time points during treatment. Octreotide's effects were assessed by comparing group means of the biochemical parameters at each time-point to mean baseline values. There were no significant changes in blood phosphate, FGF23, 1,25(OH) 2 D 3 , or TRP during octreotide treatment, consistent with a lack of efficacy of octreotide in treating TIO. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  6. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

    Science.gov (United States)

    Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

    2010-01-25

    Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

  7. Magnetic resonance enterography changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn’s disease: correlation with SES-CD and clinical-biological markers

    International Nuclear Information System (INIS)

    Stoppino, Luca Pio; Della Valle, Nicola; Rizzi, Stefania; Cleopazzo, Elsa; Centola, Annarita; Iamele, Donatello; Bristogiannis, Christos; Stoppino, Giuseppe; Vinci, Roberta; Macarini, Luca

    2016-01-01

    In recent years, the use of MRI in patients with Crohn’s disease (CD) has increased. However, few data are available on how MRI parameters of active disease change during treatment with anti-TNF and whether these changes correspond to symptoms, serum biomarkers, or endoscopic appearance. The aim of this study was to determine the changes over time in MRI parameters during treatment with anti-TNF in patients with CD, and to verify the correlation between MRI score, endoscopic appearance and clinical-biological markers. We performed a prospective single centre study of 27 patients with active CD (18 males and 9 females; median age of 27,4 ys; age range, 19–49). All patients underwent ileocolonoscopy and MRI at baseline and 26 weeks after anti-TNF therapy. Endoscopic severity was graded according to the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Magnetic Resonance Index of Activity (MaRIA) was calculated. Patients underwent clinical evaluation (CDAI) and the C-reactive protein (CRP) level was measured. The associations between variables were assessed with Pearson’s bivariate correlation analysis. A total of 135 intestinal segments were studied. The median patient age was 27,4 years, 67 % were male and the mean disease duration was 6,1 years. For induction of remission, 18 patients were treated with infliximab and 9 with adalimumab. The mean SES-CD and MaRIA scores significantly changed at week 26 (SES-CD: 14,7 ± 8,9 at baseline vs. 4,4 ± 4,6 at 26 weeks - p < 0.001; MaRIA: 41,1 ± 14,8 at baseline vs. 32,8 ± 11,7 at 26 weeks - p < 0.001). Also the CDAI and serum levels of CRP decreased significantly following treatment (p < 0.001). The overall MaRIA correlated with endoscopic score and with clinical activity (CDAI) both at baseline and at week 26 (p < 0.05). The correlation between overall MaRIA and CRP was significant only at week 26 (p < 0.001). The MaRIA has a good correlation with SES-CD, a high accuracy for prediction of endoscopic

  8. MR imaging characteristics of osteoradionecrosis of the pelvis after radiation therapy on gynecological tumors

    International Nuclear Information System (INIS)

    Schmitt, J.; Abolmaali, N.D.; Jacobi, V.; Vogl, T.J.; Hoeller, U.; Schiemann, M.; Obert, K.

    2002-01-01

    Purpose: To describe MR imaging characteristics of osteoradionecrosis (ORN) of the pelvis as a result of radiation therapy (RT) on gynecological tumors. Material and Methods: Radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on 9 women (mean age 67.5 years) with gynecological tumors to identify ORN. T 1 - and T 2 -weighted sequences and contrast-enhanced t 1 -weighted sequences with and without fat saturation were used. The patients began developing pain after the completion of RT indicating a possible ORN a which time MRI was performed. MR images were correlated with the results of clinical examinations. Results: Depending on the time elapsed after RT, ORN presented with different signal intensities. The acquired images suggested that signal changes in T 2 -weighted images as well as the different enhancement behaviour of ORN could be dependent on the time elapsed after RT. Visualisation of the affected regions was best achieved with fat-saturated T 1 -weighted sequences. CT showed increased density in the affected regions corresponding to osteosclerosis. In all cases the sacroiliac joint was affected, some times bilateraly. Conclusion: MRI is helpful in detecting and characterizing ORN. Changes in signal intensity, based on histopathological tissue changes could make a chronological classification possible. (orig.) [de

  9. Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

    Science.gov (United States)

    Sápi, Johanna; Kovács, Levente; Drexler, Dániel András; Kocsis, Pál; Gajári, Dávid; Sápi, Zoltán

    2015-01-01

    Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Our results

  10. Brain Injury After Proton Therapy or Carbon Ion Therapy for Head-and-Neck Cancer and Skull Base Tumors

    International Nuclear Information System (INIS)

    Miyawaki, Daisuke; Murakami, Masao; Demizu, Yusuke; Sasaki, Ryohei; Niwa, Yasue; Terashima, Kazuki; Nishimura, Hideki; Hishikawa, Yoshio; Sugimura, Kazuro

    2009-01-01

    Purpose: To assess the incidence of early delayed or late morbidity of Brain after particle therapy for skull base tumors and head-and-neck cancers. Methods and Materials: Between May 2001 and December 2005, 59 patients with cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic [LENT-SOMA]) and symptoms (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0). Dose-volume histograms were used to analyze the relationship between the dose and volume of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months. Results: Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose-volume histogram analyses revealed significant differences between Brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses. Conclusion: Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between Brain lobes with and without RIBCs.

  11. Modulation of the tumor vasculature and oxygenation to improve therapy

    DEFF Research Database (Denmark)

    Siemann, Dietmar W; Horsman, Michael R

    2015-01-01

    The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient...... important are the functional consequences experienced by the tumor cells residing in such environments: adaptation to hypoxia, cell quiescence, modulation of transporters and critical signaling molecules, immune escape, and enhanced metastatic potential. Together these factors lead to therapeutic barriers...

  12. Computational Modeling of Medical Images of Brain Tumor Patients for Optimized Radiation Therapy Planning

    DEFF Research Database (Denmark)

    Agn, Mikael

    In brain tumor radiation therapy, the aim is to maximize the delivered radiation dose to the targeted tumor and at the same time minimize the dose to sensitive healthy structures – so-called organs-at-risk (OARs). When planning a radiation therapy session, the tumor and the OARs therefore need...... to be delineated on medical images of the patient’s head, to be able to optimize a radiation dose plan. In clinical practice, the delineation is performed manually with limited assistance from automatic procedures, which is both time-consuming and typically suffers from poor reproducibility. There is, therefore...

  13. Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient

    International Nuclear Information System (INIS)

    Bernal-Estévez, David; Sánchez, Ramiro; Tejada, Rafael E.; Parra-López, Carlos

    2016-01-01

    Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells. T cells were obtained before and after anti-tumor therapy from peripheral blood of a 63-years old woman diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after 8 months of treatment. Using in vitro cell cultures stimulated with autologous monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we characterize by flow cytometry the phenotype of tumor associated antigens (TAAs) HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes (TILs) were performed in order to correlate both repertoires prior and after therapy. We evidence a functional recovery of T cell responsiveness to polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti-tumor therapy. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and TILs showed that whereas the TCR-Vβ04-02 clonotype is highly expressed in TILs the HER2/neu specific T cells are expressed mainly in blood after therapy, suggesting that this particular TCR was selectively enriched in blood after anti-tumor therapy. Our results show the benefits of anti-tumor therapy in a breast cancer patient with clinical complete response in

  14. Determination of the dynamics of tumor hypoxia during radiation therapy using biological imaging on mouse xenograft tumors

    OpenAIRE

    Maftei, Constantin Alin

    2013-01-01

    Background: Chronic, acute and hypoxemic hypoxia can lead to resistance to radiation therapy. The purpose of this thesis was to shed light on the role of these three hypoxia subtypes in radiotherapy. Methods: The amount of total hypoxia and hypoxia subtypes were assessed ex-vivo in xenograft tumors via (immuno-)fluorescence and H&E staining. For the non-invasive detection of hypoxia, tumor-bearing mice were injected with 18F-FMISO and underwent a dynamic PET/CT scan. The hypoxic fraction ...

  15. Potential for tumor therapy with tritiated tetracycline. Summary evaluation

    International Nuclear Information System (INIS)

    Davis, R.C.; Wood, P.; Wood, L.L.; Mendelsohn, M.L.

    1976-01-01

    Reports of tetracycline accumulation in human and animal tumors have led a number of investigators to postulate that this drug, if radio-labeled, might have potential as a therapeutic or diagnostic agent. This paper describes attempts to investigate this potential for tritiated tetracycling. The therapeutic studies demonstrated that while a significant reduction in the growth rates of transplanted tumors could be obtained by the administration of heavy doses of TTC relative to uninjected controls, similar reductions were observed in the growth rates of tumors in animals receiving unlabeled TC. In the localization studies in rodents, the concentrations of TTC in normal tissues and tumors were compared and were correlated with the corresponding concentrations of 14 C-thymidine, a measure of proliferative activity

  16. Non-Invasive Monitoring of Breast Tumor Oxygenation: A Key to Tumor Therapy Planning and Tumor Prognosis

    National Research Council Canada - National Science Library

    Liu, Hanli

    2004-01-01

    .... The aims have included (1) to evaluate a single-channel, dual wavelength, NIR, frequency-domain oximeter and the algorithms for obtaining tumor HbO2 against tumor PO2 measured by 19F magnetic resonance imaging (MRI), (2...

  17. Enhanced tumor responses through therapies combining CCNU, MISO and radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, S.A.

    1984-01-01

    Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

  18. The host immunological response to cancer therapy: An emerging concept in tumor biology.

    Science.gov (United States)

    Voloshin, Tali; Voest, Emile E; Shaked, Yuval

    2013-07-01

    Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction-both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Tumor sterilization dose and radiation induced change of the brain tissue in radiotherapy of brain tumors

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Takano, Shingo

    1987-01-01

    Ninety-seven patients with brain tumors (38 gliomas, 26 brain metastases, 18 sellar tumors, 15 others) were treated by cobalt gamma ray or proton radiotherapy. In this study, normal brain injury due to radiation was analysed in terms of time-dose-fractionation (TDF), nominal standard dose (NSD) by the Ellis formula and NeuNSD by a modification in which the N exponent was -0.44 and the T exponent was -0.06. Their calculated doses were analysed in relationship to the normal brain radiation induced change (RIC) and the tumor sterilization dose. All brain tumors with an exception of many patients with brain metastases were received a surgical extirpation subtotally or partially prior to radiotherapy. And all patients with glioma and brain metastasis received also immuno-chemotherapy in the usual manner during radiotherapy. The calculated dose expressed by NeuNSD and TDF showed a significant relationship between a therapeutic dose and a postradiation time in terms of the appearance of RIC. It was suggested that RIC was caused by a dose over 800 in NeuNSD and a dose over 70 in TDF. Furthermore, it was suggested that an aged patient and a patient who had the vulnerable brain tissue to radiation exposure in the irradiated field had the high risk of RIC. On the other hand, our results suggested that the tumor sterilization dose should be over 1,536 NeuNSD and the irradiated method should be further considered in addition to the radiobiological concepts for various brain tumors. (author)

  20. Disruption of tumor neovasculature by microbubble enhanced ultrasound: a potential new physical therapy of anti-angiogenesis.

    Science.gov (United States)

    Liu, Zheng; Gao, Shunji; Zhao, Yang; Li, Peijing; Liu, Jia; Li, Peng; Tan, Kaibin; Xie, Feng

    2012-02-01

    Tumor angiogenesis is of vital importance to the growth and metastasis of solid tumors. The angiogenesis is featured with a defective, leaky and fragile vascular construction. Microbubble enhanced ultrasound (MEUS) cavitation is capable of mechanical disruption of small blood vessels depending on effective acoustic pressure amplitude. We hypothesized that acoustic cavitation combining high-pressure amplitude pulsed ultrasound (US) and circulating microbubble could potentially disrupt tumor vasculature. A high-pressure amplitude, pulsed ultrasound device was developed to induce inertial cavitation of circulating microbubbles. The tumor vasculature of rat Walker 256 was insonated percutaneously with two acoustic pressures, 2.6 MPa and 4.8 MPa, both with intravenous injection of a lipid microbubble. The controls were treated by the ultrasound only or sham ultrasound exposure. Contrast enhanced ultrasound (CEUS) and histology were performed to assess tumor circulation and pathological changes. The CEUS results showed that the circulation of Walker 256 tumors could be completely blocked off for 24 hours in 4.8 MPa treated tumors. The CEUS gray scale value (GSV) indicated that there was significant GSV drop-off in both of the two experimental groups but none in the controls. Histology showed that the tumor microvasculature was disrupted into diffuse hematomas accompanied by thrombosis, intercellular edema and multiple cysts formation. The 24 hours of tumor circulation blockage resulted in massive necrosis of the tumor. MEUS provides a new, simple physical method for anti-angiogenic therapy and may have great potential for clinical applications. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  1. The changing motivation of massage therapy students.

    Science.gov (United States)

    Finch, P

    2007-05-01

    The study was conducted in order to determine whether the level of motivation related to intrinsic (people-oriented) and extrinsic (external reward) value complexes in a class of massage therapy students changed during their professional education. The research was a quasi-experimental within-subject design, in which survey data was collected from students on their first day in the massage therapy program and again towards the end of their final term. The data were collated and summarized, and the differences in motivation scores were assessed using Fisher's Least Significant Difference procedure. The results support the hypothesis that massage therapy students are motivated more strongly by intrinsic than extrinsic rewards both at the commencement of their studies and as they approach entry to practice. Also evident from the data is the fact that the students' motivation changed during their professional studies. This change involved a significant decrease in the level of intrinsic motivation and significant increase in the level of extrinsic motivation. Thus, although intrinsic motivation reduced while extrinsic motivation increased, the former remained the more powerful influence. Professional programs should consider the balance between intrinsic and extrinsic student motivation and attempt to control influences that might shift this such that the humanistic / altruistic mission of health care is undermined.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Progress toward overcoming hypoxia-induced resistance to solid tumor therapy

    International Nuclear Information System (INIS)

    Karakashev, Sergey V; Reginato, Mauricio J

    2015-01-01

    Hypoxic tumors are associated with poor clinical outcome for multiple types of human cancer. This may be due, in part, to hypoxic cancer cells being resistant to anticancer therapy, including radiation therapy, chemotherapy, and targeted therapy. Hypoxia inducible factor 1, a major regulator of cellular response to hypoxia, regulates the expression of genes that are involved in multiple aspects of cancer biology, including cell survival, proliferation, metabolism, invasion, and angiogenesis. Here, we review multiple pathways regulated by hypoxia/hypoxia inducible factor 1 in cancer cells and discuss the latest advancements in overcoming hypoxia-mediated tumor resistance

  4. Physiologic Effect of Stent Therapy for Inferior Vena Cava Obstruction Due to Malignant Liver Tumor

    International Nuclear Information System (INIS)

    Kishi, Kazushi; Sonomura, Tetsuo; Fujimoto, Hisashi; Kimura, Masashi; Yamada, Katsuya; Sato, Morio; Juri, Masanobu

    2006-01-01

    Purpose. To understand systemic the influence of stent therapy for inferior vena cava (IVC) obstruction due to advanced liver tumor. Methods. Seven patients with symptomatic IVC obstruction due to advanced primary (n 4) or secondary (n = 3) liver tumor were subjected to stent therapy. Enrollment criteria included high IVC pressure over 15 mmHg and the presence of edema and ascites. Z-stents were deployed using coaxial sheath technique via femoral venous puncture. Physiologic and hematobiochemical parameters were analyzed. Results. All procedures were successful, and the stents remained patent until patient death. Promptly after stent placement, the IVC flow recovered, and the venous blood pressure in the IVC below the obstruction level showed a significant decrease from 20.8 ± 1.2 mmHg (mean ± SE) to 10.7 ± 0.7 mmHg (p 0.6) with the urine volume increase, and with the decreased volume of edema and ascites. The urine volume increase correlated well with the decrement of edema, but not with that of ascites. Improvements for various durations in the levels of blood urea nitrogen, serum creatinine, lactate dehydrogenase, fibrinogen, and platelet count were found (p < 0.05). These hematobiochemical changes were well correlated with each other and with the decrement of ascites. Two patients showed a low blood sodium level of 128.5 mEq/l after intensive natriuresis, and one of them died on day 21 with hepatic failure, which was interpreted as maladaptation aggravation. The mean survival time was 94.1 ± 34.1 days (mean ± SD), ranging from 21 to 140 days after stent treatment. Conclusion. The stent therapy for IVC obstruction due to malignant liver tumors was followed by a series of physiologic and hematobiochemical consequences, most of them favorable but some possibly unfavorable. Rational interpretations and predictions of sequelae based on physiologic science including cardiology, hepatology, and nephrology would facilitate the best management of stent therapy for

  5. 31P NMR spectroscopy of tumors in the evaluation of response to therapy

    International Nuclear Information System (INIS)

    Sijens, P.E.

    1988-01-01

    In this thesis the effects of different kinds of therapy on tumour metabolism were investigated by in vivo 31P NMR spectroscopy. From the first five chapters (laboratory-animal studies) it turns out that after radiotherapy as well as after hyperthermy or chemoterapy changes can be observed in the 31P NMR spectra of tumours. In a number of cases a durable decline occurred in the ratio of the high-energetic adenosinephosphate (ATP) and the low-energeic anorganic phosphate, cuased by the mortification of tumourcells. On the other hand, tumour regression after effective chemotherapy resulted in a growth of the ATP/Pi ratio. In one case a temporary drop occurred which could be related to a temporary decrease in tumour perfusion. In anoter case a temporary drop of the ATP/Pi ratio correlated with resistence against treatment with cis-diaminodichoroplatina. In contrast with the changes in ATP/Pi ratio, the changes, after (chemo)therapy, in tumour pH do not seem to be related with the respons of the tumour. The results of the laboratory-animal experiments indicate that in vivo 31P NMR spectroscopy could be applied in the clinic in order to establish betime the response of tumours on therapy. In ch. 6 initial experiences with clinical NMR spectroscopy of human breast cancer are described. The results indicate that by 31P NMR spectroscopy malignant breast tissues can be discerned from normal breast tissues, following radiotherapy and subsequent tumour regression, in the spectrum of the tumorous region an intense PCr signal developed which appeared to reflect a metabolic change in the tumous itself. 177 refs.; 27 figs.; 6 tabs

  6. Predicting oropharyngeal tumor volume throughout the course of radiation therapy from pretreatment computed tomography data using general linear models

    International Nuclear Information System (INIS)

    Yock, Adam D.; Kudchadker, Rajat J.; Rao, Arvind; Dong, Lei; Beadle, Beth M.; Garden, Adam S.; Court, Laurence E.

    2014-01-01

    Purpose: The purpose of this work was to develop and evaluate the accuracy of several predictive models of variation in tumor volume throughout the course of radiation therapy. Methods: Nineteen patients with oropharyngeal cancers were imaged daily with CT-on-rails for image-guided alignment per an institutional protocol. The daily volumes of 35 tumors in these 19 patients were determined and used to generate (1) a linear model in which tumor volume changed at a constant rate, (2) a general linear model that utilized the power fit relationship between the daily and initial tumor volumes, and (3) a functional general linear model that identified and exploited the primary modes of variation between time series describing the changing tumor volumes. Primary and nodal tumor volumes were examined separately. The accuracy of these models in predicting daily tumor volumes were compared with those of static and linear reference models using leave-one-out cross-validation. Results: In predicting the daily volume of primary tumors, the general linear model and the functional general linear model were more accurate than the static reference model by 9.9% (range: −11.6%–23.8%) and 14.6% (range: −7.3%–27.5%), respectively, and were more accurate than the linear reference model by 14.2% (range: −6.8%–40.3%) and 13.1% (range: −1.5%–52.5%), respectively. In predicting the daily volume of nodal tumors, only the 14.4% (range: −11.1%–20.5%) improvement in accuracy of the functional general linear model compared to the static reference model was statistically significant. Conclusions: A general linear model and a functional general linear model trained on data from a small population of patients can predict the primary tumor volume throughout the course of radiation therapy with greater accuracy than standard reference models. These more accurate models may increase the prognostic value of information about the tumor garnered from pretreatment computed tomography

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Indocyanine green loaded graphene oxide for high-efficient photoacoustic tumor therapy

    Directory of Open Access Journals (Sweden)

    Baoyun Yan

    2016-07-01

    Full Text Available Photoacoustic therapy, using the photoacoustic effect of agents for selectively killing tumor cells, has shown promising for treating tumor. Utilization of high optical absorption probes can help to effectively improve the photoacoustic therapy efficiency. Herein, we report a novel high-absorption photoacoustic probe that is composed of indocyanine green (ICG and graphene oxide (GO, entitled GO-ICG, for photoacoustic therapy. The attached ICG with narrow absorption spectral profile has strong optical absorption in the infrared region. The absorption spectrum of the GO-ICG solution reveals that the GO-ICG particles exhibited a 10-fold higher absorbance at 780nm (its peak absorbance as compared with GO. Importantly, ICG’s fluorescence is quenched by GO via fluorescence resonance energy transfer. As a result, GO-ICG can high-efficiently convert the absorbed light energy to acoustic wave under pulsed laser irradiation. We further demonstrate that GO-ICG can produce stronger photoacoustic wave than the GO and ICG alone. Moreover, we conjugate this contrast agent with integrin αvβ3 mono-clonal antibody to molecularly target the U87-MG human glioblastoma cells for selective tumor cell killing. Finally, our results testify that the photoacoustic therapy efficiency of GO-ICG is higher than the existing photoacoustic therapy agent. Our work demonstrates that GO-ICG is a high-efficiency photoacoustic therapy agent. This novel photoacoustic probe is likely to be an available candidate for tumor therapy.

  9. Combined therapy of radiation and hyperthermia on a metastatic tumor of angiosarcoma

    International Nuclear Information System (INIS)

    Yasuda, Hiroshi; Kitayama, Yoshiaki

    1987-01-01

    A combined therapy of radiation and hyperthermia is said to be fairly effective when applied to certain malignant tumors. However, the utility of this therapy for the treatment of angiosarcoma has not been well discussed. Recently, we have had a chance to treat a patient with metastatic angiosarcoma of the neck by using this combined therapy. In this paper, the clinical course of this patient and the availability of this combined therapy for angiosarcoma is reported. The patient was a 77-year-old man, having a primary lesion on the head and a metastatic tumor over the left cheek and neck. This combined therapy was used for the treatment of the metastatic tumor which caused severe pain and uncontrollable bleeding. The results were considered good ; the tumor decreased in size, pain disappeared and no further bleeding or severe side effects were observed. Though the patient died of another metastatic lesion which could not be treated with this combined therapy because the area of its localization could not allow placement in our hyperthermal apparatus, it is concluded that the combined therapy of radiation and hyperthermia is useful selectively for the treatment for angiosarcoma. (author)

  10. iNOS+ macrophages: potential alternate and tool for effective tumor therapy

    International Nuclear Information System (INIS)

    Prakash, Hridayesh; KIug, Felix; Jäger, Dirk; Hammerling, Gunter; Beckhove, Philipp

    2014-01-01

    Inefficient migration of immune effector cells in the tumor is a major limitation of effective therapy against solid tumors. This is due to immunosuppressive micro environment and impermissive endothelium which protects tumors from immune attack which is attributed to massive infiltration of tumors by macrophages which are known as tumor associated macrophages which are INOS low , Arginase- 1+ , Ym- 1+ , CD206 + (known as M2 or alternatively activated or tumor associated macrophages). Accumulation of M2 has been associated with the poor prognosis in the majority of cancer patients. Radiotherapy has recently been introduced as a potential strategy to improve cancer immunotherapy and tumor immune rejection. This is the only clinically advanced approach for noninvasive, site-specific intervention in cancer patients. Majority of cancer patients are routinely irradiated with therapeutic and high doses of γ-radiations which frequently manifest severe local/systemic acute. Low dose radiation (LDR) on the other hand may provide good alternatives of HDR for avoiding such toxicities. In this line, our pioneer study demonstrated that local/systemic low dose irradiation of tumors (2 Gy) effectively modified tumor micro environment and facilitated infiltration of peripheral immune effectors cells (T-cells) in neuroendocrine tumor of pancreas called insulinoma in RIP1-Tag5 (RT5) mice and primary human pancreatic carcinoma. Such tumor infiltration of T cells remained strictly dependent on iNOS + peritumoral macrophages. Our study also explicitly revealed that adoptive transfer of iNOS expressing macrophages in unirradiated RIP1-Tag5 (RT5) also offer a promising intervention to establish those populations of macrophages in the tumor tissue that enable therapeutic efficacy of cancer immunotherapy. We here demonstrate the critical role of iNOS + macrophages in joint regulation of tumor micro environment (angiogenesis) as well as effector T cell recruitment into tumor tissue and

  11. Modifiers of radiation response in tumor therapy: strategies and expectations

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1982-01-01

    The administration of two (or more) cytotoxic agents to widen the differential between the responses of tumor and normal tissues depends upon the biological properties of the agents in the cells and tissues, their interactive potential, and the strategy employed in their administration. Assuming that one agent is ionizing radiation, and considering response modification in broad terms, the qualitative features of various strategies are developed for physical as well as chemical modifies. The heterogeneity of human tumor cells and the compensatory mechanisms of normal tissues following injury are identified as topical areas requiring sustained research effort. Finally, estimates are developed for the degree of improvement required from a response modifier to effect significant improvements in tumor cure rates

  12. Modifiers of radiation response in tumor therapy: strategies and expectations

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1982-01-01

    The administration of two (or more) cytotoxic agents to widen the differential between the responses of tumor and normal tissues depends upon the biological properties of the agents in the cells and tissues, their interactive potential, and the strategy employed in their administration. Assuming that one agent is ionizing radiation, and considering response modification in broad terms, the qualitative features of various strategies are developed for physical as well as chemical modifiers. The heterogeneity of human tumor cells and the compensatory mechanisms of normal tissues following injury are identified as topical areas requiring sustained research effort. Finally, estimates are developed for the degree of improvement from a response modifier to effect significant improvements in tumor cure rates

  13. Laser photoradiation therapy in the treatment of malignant tumors

    International Nuclear Information System (INIS)

    Tomio, L.; Corti, L.; Polico, C.

    1987-01-01

    Photoradiation theraphy or, as more recently defined, photodynamic theraphy (PDT) has been effective in the treatment of several kinds of cancers, above all the skin, lung, esophagus and bladder. It is based on the preferential retention by tumor and photosensitizing properties of certains porphyrins.It has been initiated to investigate this technique experimentally in 1978 and clinically in september 1982, with report of the initial results in 38 patients in 1985. In this paper the more recent experience of PDT in 18 patients affected by different tumors and treated with a new double argon-dye laser system is described. These tumors included 8 carcinomas of the esophagus, 5 basal cell skin cancers, 2 carcinomas of the lung, 2 squamous cell carcinomas of the oral cavity and 1 early gastric cancer. Clinical results and technical problems of PDT are discussed

  14. Mechanisms of Change in Interpersonal Therapy (IPT)

    Science.gov (United States)

    Lipsitz, Joshua D.; Markowitz, John C.

    2014-01-01

    Although interpersonal therapy (IPT) has demonstrated efficacy for mood and other disorders, little is known about how IPT works. We present interpersonal change mechanisms that we hypothesize account for symptom change in IPT. IPT’s interpersonal model integrates both relational theory, building on work by Sullivan, Bowlby, and others, and insights based on research findings regarding stress, social support, and illness to highlight contextual factors thought to precipitate and maintain psychiatric disorders. IPT frames therapy around a central interpersonal problem in the patient’s life, a current crisis or relational predicament that is disrupting social support and increasing interpersonal stress. By mobilizing and working collaboratively with the patient to resolve (better manage or negotiate) this problem, IPT seeks to activate several interpersonal change mechanisms. These include: 1) enhancing social support, 2) decreasing interpersonal stress, 3) facilitating emotional processing, and 4) improving interpersonal skills. We hope that articulating these mechanisms will help therapists to formulate cases and better maintain focus within an IPT framework. We propose interpersonal mechanisms that might explain how IPT’s interpersonal focus leads to symptom change. Future work needs to specify and test candidate mediators in clinical trials of IPT. We anticipate that pursuing this more systematic strategy will lead to important refinements and improvements in IPT and enhance its application in a range of clinical populations. PMID:24100081

  15. Mechanisms of change in interpersonal therapy (IPT).

    Science.gov (United States)

    Lipsitz, Joshua D; Markowitz, John C

    2013-12-01

    Although interpersonal therapy (IPT) has demonstrated efficacy for mood and other disorders, little is known about how IPT works. We present interpersonal change mechanisms that we hypothesize account for symptom change in IPT. Integrating relational theory and insights based on research findings regarding stress, social support, and illness, IPT highlights contextual factors thought to precipitate and maintain psychiatric disorders. It frames therapy around a central interpersonal problem in the patient's life, a current crisis or relational predicament that is disrupting social support and increasing interpersonal stress. By mobilizing and working collaboratively with the patient to resolve this problem, IPT seeks to activate several interpersonal change mechanisms. These include: 1) enhancing social support, 2) decreasing interpersonal stress, 3) facilitating emotional processing, and 4) improving interpersonal skills. We hope that articulating these mechanisms will help therapists to formulate cases and better maintain focus within an IPT framework. Here we propose interpersonal mechanisms that might explain how IPT's interpersonal focus leads to symptom change. Future work needs to specify and test candidate mediators in clinical trials. We anticipate that pursuing this more systematic strategy will lead to important refinements and improvements in IPT and enhance its application in a range of clinical populations. © 2013.

  16. Principles of radiation therapy in the treatment of vaginal tumors

    International Nuclear Information System (INIS)

    Nori, D.

    1987-01-01

    Vaginal tumors constitute about 1-1.5% of all gynecological cancers. However, there is a great variety of histological types of vaginal cancers that affect females of all ages. Characteristically embryonal rhabdomyosarcoma (sarcoma botryoides) occurs in infants; diethylstilbestrol-induced clear cell adenocarcinomas in teenage girls; and squamous cell carcinoma, melanoma, sarcoma, and adenocarcinoma in adult women. Because of the rarity of these tumors, few clinicians gain wide experience in their treatment. Treatment of these three clinical entities in three different age groups is presented in this chapter

  17. Chimeric antigen receptor T-cell therapy for solid tumors

    Directory of Open Access Journals (Sweden)

    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.

  18. Tumor initiating cells in malignant gliomas: biology and implications for therapy.

    Science.gov (United States)

    Hadjipanayis, Costas G; Van Meir, Erwin G

    2009-04-01

    A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas.

  19. Automatic Multiple-Needle Surgical Planning of Robotic-Assisted Microwave Coagulation in Large Liver Tumor Therapy.

    Directory of Open Access Journals (Sweden)

    Shaoli Liu

    Full Text Available The "robotic-assisted liver tumor coagulation therapy" (RALTCT system is a promising candidate for large liver tumor treatment in terms of accuracy and speed. A prerequisite for effective therapy is accurate surgical planning. However, it is difficult for the surgeon to perform surgical planning manually due to the difficulties associated with robot-assisted large liver tumor therapy. These main difficulties include the following aspects: (1 multiple needles are needed to destroy the entire tumor, (2 the insertion trajectories of the needles should avoid the ribs, blood vessels, and other tissues and organs in the abdominal cavity, (3 the placement of multiple needles should avoid interference with each other, (4 an inserted needle will cause some deformation of liver, which will result in changes in subsequently inserted needles' operating environment, and (5 the multiple needle-insertion trajectories should be consistent with the needle-driven robot's movement characteristics. Thus, an effective multiple-needle surgical planning procedure is needed. To overcome these problems, we present an automatic multiple-needle surgical planning of optimal insertion trajectories to the targets, based on a mathematical description of all relevant structure surfaces. The method determines the analytical expression of boundaries of every needle "collision-free reachable workspace" (CFRW, which are the feasible insertion zones based on several constraints. Then, the optimal needle insertion trajectory within the optimization criteria will be chosen in the needle CFRW automatically. Also, the results can be visualized with our navigation system. In the simulation experiment, three needle-insertion trajectories were obtained successfully. In the in vitro experiment, the robot successfully achieved insertion of multiple needles. The proposed automatic multiple-needle surgical planning can improve the efficiency and safety of robot-assisted large liver tumor

  20. Automatic Multiple-Needle Surgical Planning of Robotic-Assisted Microwave Coagulation in Large Liver Tumor Therapy.

    Science.gov (United States)

    Liu, Shaoli; Xia, Zeyang; Liu, Jianhua; Xu, Jing; Ren, He; Lu, Tong; Yang, Xiangdong

    2016-01-01

    The "robotic-assisted liver tumor coagulation therapy" (RALTCT) system is a promising candidate for large liver tumor treatment in terms of accuracy and speed. A prerequisite for effective therapy is accurate surgical planning. However, it is difficult for the surgeon to perform surgical planning manually due to the difficulties associated with robot-assisted large liver tumor therapy. These main difficulties include the following aspects: (1) multiple needles are needed to destroy the entire tumor, (2) the insertion trajectories of the needles should avoid the ribs, blood vessels, and other tissues and organs in the abdominal cavity, (3) the placement of multiple needles should avoid interference with each other, (4) an inserted needle will cause some deformation of liver, which will result in changes in subsequently inserted needles' operating environment, and (5) the multiple needle-insertion trajectories should be consistent with the needle-driven robot's movement characteristics. Thus, an effective multiple-needle surgical planning procedure is needed. To overcome these problems, we present an automatic multiple-needle surgical planning of optimal insertion trajectories to the targets, based on a mathematical description of all relevant structure surfaces. The method determines the analytical expression of boundaries of every needle "collision-free reachable workspace" (CFRW), which are the feasible insertion zones based on several constraints. Then, the optimal needle insertion trajectory within the optimization criteria will be chosen in the needle CFRW automatically. Also, the results can be visualized with our navigation system. In the simulation experiment, three needle-insertion trajectories were obtained successfully. In the in vitro experiment, the robot successfully achieved insertion of multiple needles. The proposed automatic multiple-needle surgical planning can improve the efficiency and safety of robot-assisted large liver tumor therapy

  1. Referent 3D tumor model at cellular level in radionuclide therapy

    International Nuclear Information System (INIS)

    Spaic, R.; Ilic, R.D.; Petrovic, B.J.

    2002-01-01

    Aim Conventional internal dosimetry has a lot of limitations because of tumor dose nonuniformity. The best approach for absorbed dose at cellular level for different tumors in radionuclide therapy calculation is Monte Carlo method. The purpose of this study is to introduce referent tumor 3D model at cellular level for Monte Carlo simulation study in radionuclide therapy. Material and Methods The moment when tumor is detectable and when same therapy can start is time period in which referent 3D tumor model at cellular level was defined. In accordance with tumor growth rate at that moment he was a sphere with same radius (10 000 μm). In that tumor there are cells or cluster of cells, which are randomly distributed spheres. Distribution of cells/cluster of cells can be calculated from histology data but it was assumed that this distribution is normal with the same mean value and standard deviation (100±50 mm). Second parameter, which was selected to define referent tumor, is volume density of cells (30%). In this referent tumor there are no necroses. Stroma is defined as space between spheres with same concentration of materials as in spheres. Results: Referent tumor defined on this way have about 2,2 10 5 cells or cluster of cells random distributed. Using this referent 3D tumor model and for same concentration of radionuclides (1:100) and energy of beta emitters (1000 keV) which are homogeneously distributed in labeled cells absorbed dose for all cells was calculated. Simulations are done using FOTELP Monte Carlo code, which is modified for this purposes. Results of absorbed dose in cells are given in numerical values (1D distribution) and as the images (2D or 3D distributions). Conclusion Geometrical module for Monte Carlo simulation study can be standardized by introducing referent 3D tumor model at cellular level. This referent 3D tumor model gives most realistic presentation of different tumors at the moment of their detectability. Referent 3D tumor model at

  2. Image-Based Monitoring of Magnetic Resonance-Guided Thermoablative Therapies for Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rempp, Hansjoerg, E-mail: hansjoerg.rempp@med.uni-tuebingen.de; Clasen, Stephan [Eberhard Karls University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Pereira, Philippe L. [SLK-Kliniken, Clinic for Radiology, Nuclear Medicine, and Minimal Invasive Therapies (Germany)

    2012-12-15

    Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.

  3. Image-Based Monitoring of Magnetic Resonance-Guided Thermoablative Therapies for Liver Tumors

    International Nuclear Information System (INIS)

    Rempp, Hansjörg; Clasen, Stephan; Pereira, Philippe L.

    2012-01-01

    Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.

  4. Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy.

    Science.gov (United States)

    Williams, Ross; Hudson, John M; Lloyd, Brendan A; Sureshkumar, Ahthavan R; Lueck, Gordon; Milot, Laurent; Atri, Mostafa; Bjarnason, Georg A; Burns, Peter N

    2011-08-01

    To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US). The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected. In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome. © RSNA, 2011.

  5. 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.

  6. Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice

    International Nuclear Information System (INIS)

    Itasaka, Satoshi; Komaki, Ritsuko; Herbst, Roy S.; Shibuya, Keiko; Shintani, Tomoaki D.D.S.; Hunter, Nancy R. M.S.; Onn, Amir; Bucana, Corazon D.; Milas, Luka; Ang, K. Kian; O'Reilly, Michael S.

    2007-01-01

    Purpose: Clinical trials of antiangiogenic agents used alone for advanced malignancy have been disappointing but preclinical studies suggest that the addition of radiation therapy could improve antitumor efficacy. To test the hypothesis that antiangiogenic therapy combined with radiation therapy can overcome the limitations of antiangiogenic monotherapy, we studied the effects of endostatin combined with radiation on the growth and vascularization of A431 human epidermoid carcinomas growing intramuscularly in the legs of mice. Methods and Materials: Mice with established A431 human epidermoid leg tumors were treated with radiation, endostatin, both radiation and endostatin, or vehicle control. The experiment was repeated and mice from each group were killed at 2, 7, and 10 days after irradiation so that tumor tissue could be obtained to further analyze the kinetics of the antitumor, antivascular, and antiangiogenic response to therapy. Results: Endostatin enhanced the antitumor effects of radiation, and prolonged disease-free survival was observed in the combined treatment group. Endothelial cell proliferation was increased in tumors after irradiation but was blocked by the concurrent administration of endostatin, and the combination of endostatin with radiation enhanced endothelial cell apoptosis within 48 h after irradiation. Expression of vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 were increased in tumors after irradiation, and this increase was blocked by concurrent administration of endostatin. Conclusion: These data indicate that endostatin can block tumor revascularization after radiation therapy and thereby augment radioresponse

  7. Microwave pumped high-efficient thermoacoustic tumor therapy with single wall carbon nanotubes.

    Science.gov (United States)

    Wen, Liewei; Ding, Wenzheng; Yang, Sihua; Xing, Da

    2016-01-01

    The ultra-short pulse microwave could excite to the strong thermoacoustic (TA) shock wave and deeply penetrate in the biological tissues. Based on this, we developed a novel deep-seated tumor therapy modality with mitochondria-targeting single wall carbon nanotubes (SWNTs) as microwave absorbing agents, which act efficiently to convert ultra-short microwave energy into TA shock wave and selectively destroy the targeted mitochondria, thereby inducing apoptosis in cancer cells. After the treatment of SWNTs (40 μg/mL) and ultra-short microwave (40 Hz, 1 min), 77.5% of cancer cells were killed and the vast majority were caused by apoptosis that initiates from mitochondrial damage. The orthotopic liver cancer mice were established as deep-seated tumor model to investigate the anti-tumor effect of mitochondria-targeting TA therapy. The results suggested that TA therapy could effectively inhibit the tumor growth without any observable side effects, while it was difficult to achieve with photothermal or photoacoustic therapy. These discoveries implied the potential application of TA therapy in deep-seated tumor models and should be further tested for development into a promising therapeutic modality for cancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Tumor - host immune interactions in Ewing sarcoma : implications for therapy

    NARCIS (Netherlands)

    Berghuis, Dagmar

    2012-01-01

    In this thesis, we report on various aspects of tumor - host (immune) interactions in Ewing sarcoma patients with the aim to obtain leads for immunotherapeutic or targeted treatment strategies. We demonstrate a key role for interferon gamma (IFNg) in enhancing both Ewing sarcoma immunogenicity and

  9. Radiation therapy for glomus tumors of the temporal bone

    International Nuclear Information System (INIS)

    Dall'Igna, Celso; Antunes, Marcelo B.

    2005-01-01

    The treatment of glomic tumors has been controversial since its first description. It can be done with surgery, radiotherapy or just expectation. Aim: the objective of this paper was to evaluate the effectiveness and complications of radiotherapy.Study Design: clinical with transversal cohort. Material and method: it was made a retrospective review in the charts of the patients with glomus jugular tumors treated with radiotherapy. Disease control was determined by (1) no progression of symptoms or cranial nerve dysfunction or (2) no progression of the lesion in radiological follow-up. It was also evaluated the follow-up period and the sequelae of the treatment. Results: twelve patients were included, 8 of then women. The follow-up period was from 3 to 35 years, with a media of 11,6 years. The main symptoms were: hearing loss, pulsate tinnitus, dizziness and vertigo. The signs were pulsate retrotympanic mass, facial palsy and cofosis. The tumors were staged using Fischs classification. The radiotherapy was performed with linear accelerator with dose ranging from 4500-5500 in 4-6 weeks. In the follow-up period were possible to identify sequelaes like dermatitis, meatal stenosis, cofosis and facial palsy. Discussion: the signs and symptoms were the same found in the medical literature. The type and dosages of the radiotherapy were also the same of others reports. All patients had improvement of the symptoms and only one was not considered as having disease controlled. Complications were, in general, minor complications, with exception of the cofosis and facial palsy. Conclusion: radiotherapy is a viable alternative to treatment of these tumors because their good response and low level of complications. It should be considered specially in advanced tumors where a surgical procedure could bring a high level of morbidity. (author)

  10. Study on therapy of 188Re labelled stannic sulfur suspension in nude mice bearing human colon tumor

    International Nuclear Information System (INIS)

    Li Huiyuan; Wu Yuanfang; Dong Mo

    2003-01-01

    The effect of therapy, tissue distribution and stability are studied in nude mice bearing human colon tumor after injections of 188 Re labelled stannic sulfur suspension. The tissues are observed with electric microscope. The results show that 188 Re labelled stannic sulfur suspension is stabilized in the tumor and its inhibitive effects on human colon tumor cells are obvious. 188 Re labelled stannic sulfur suspension is a potential radiopharmaceuticals for therapy of human tumor

  11. Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy

    International Nuclear Information System (INIS)

    Ran, Sophia; Thorpe, Philip E.

    2002-01-01

    Purpose: (1) To determine whether exposure of phosphatidylserine (PS) occurs on vascular endothelium in solid tumors in mice. (2) To determine whether PS exposure can be induced on viable endothelial cells in tissue culture by conditions present in the tumor microenvironment. Methods and Materials: Externalized PS in vivo was detected by injecting mice with a monoclonal anti-PS antibody and examining frozen sections of tumors and normal tissues for anti-PS antibody bound to vascular endothelium. Apoptotic cells were identified by anti-active caspase-3 antibody or by TUNEL assay. PS exposure on cultured endothelial cells was determined by 125 I-annexin V binding. Results: Anti-PS antibody bound specifically to vascular endothelium in six tumor models. The percentage of PS-positive vessels ranged from 4% to 40% in different tumor types. Vascular endothelium in normal organs was unstained. Very few tumor vessels expressed apoptotic markers. Hypoxia/reoxygenation, acidity, inflammatory cytokines, thrombin, or hydrogen peroxide induced PS exposure on cultured endothelial cells without causing loss of viability. Conclusions: Vascular endothelial cells in tumors, but not in normal tissues, externalize PS. PS exposure might be induced by tumor-associated oxidative stress and activating cytokines. PS is an abundant and accessible marker of tumor vasculature and could be used for tumor imaging and therapy

  12. Tumor cell killing effect of boronated dipeptide. Boromethylglycylphenylalanine on boron neutron capture therapy for malignant brain tumors

    International Nuclear Information System (INIS)

    Takagaki, Masao; Ono, Koji; Masunaga, Shinichiro; Kinashi, Yuko; Kobayashi, Toru; Oda, Yoshifumi; Kikuchi, Haruhiko; Spielvogel, B.F.

    1994-01-01

    The killing effect of Boron Neutron Capture Therapy; BNCT, is dependant on the boron concentration ratio of tumor to normal brain (T/N ratio), and also that of tumor to blood (T/B ratio). The clinical boron carrier of boro-captate (BSH) showed the large T/N ratio of ca. 8, however the T/B ratio was around 1, which indicated nonselective accumulation into tumor. Indeed high boron concentration of blood restrict the neutron irradiation dose in order to circumvent the normal endothelial damage, especially in the case of deeply seated tumor. Phenylalanine analogue of para borono-phenylalanine (BPA) is an effective boron carrier on BNCT for malignant melanoma. For the BNCT on brain tumors, however, BPA concentration in normal brain was reported to be intolerably high. In order to improve the T/N ratio of BPA in brain, therefore, a dipeptide of boromethylglycylphenylalanine (BMGP) was synthesized deriving from trimethylglycine conjugated with BPA. It is expected to be selectively accumulated into tumor with little uptake into normal brain. Because a dipeptide might not pass through the normal blood brain barrier (BBB). Its killing effect on cultured glioma cell, T98G, and its distribution in rat brain bearing 9L glioma have been investigated in this paper. The BNCT effect of BMGP on cultured cells was nearly triple in comparison with DL-BPA. The neutron dose yielding 1% survival ratio were 7x10 12 nvt for BMGP and 2x10 13 nvt for BPA respectively on BNCT after boron loading for 16 hrs in the same B-10 concentration of 20ppm. Quantitative study of boron concentration via the α-auto radiography and the prompt gamma ray assay on 9L brain tumor rats revealed that T/N ratio and T/B ratio are 12.0 and 3.0 respectively. Those values are excellent for BNCT use. (author)

  13. Digital tumor fluoroscopy (DTF)--a new direct imaging system in the therapy planning for brain tumors.

    Science.gov (United States)

    Herbst, M; Fröder, M

    1990-01-01

    Digital Tumor Fluoroscopy is an expanded x-ray video chain optimized to iodine contrast with an extended Gy scale up to 64000 Gy values. Series of pictures are taken before and after injection of contrast medium. With the most recent unit, up to ten images can be taken and stored. The microprogrammable processor allows the subtraction of images recorded at any moment of the examination. Dynamic views of the distribution of contrast medium in the intravasal and extravasal spaces of brain and tumor tissue are gained by the subtraction of stored images. Tumors can be differentiated by studying the storage and drainage behavior of the contrast medium during the period of examination. Meningiomas store contrast medium very intensively during the whole time of investigation, whereas astrocytomas grade 2-3 pick it up less strongly at the beginning and release it within 2 min. Glioblastomas show a massive but delayed accumulation of contrast medium and a decreased flow-off-rate. In comparison with radiography and MR-imaging the most important advantage of Digital Tumor Fluoroscopy is that direct information on tumor localization is gained in relation to the skull-cap. This enables the radiotherapist to mark the treatment field directly on the skull. Therefore it is no longer necessary to calculate the tumor volume from several CT scans for localization. In radiotherapy Digital Tumor Fluoroscopy a unit combined with a simulator can replace CT planning. This would help overcome the disadvantages arising from the lack of a collimating system, and the inaccuracies which result from completely different geometric relationships between a CT unit and a therapy machine.

  14. Hypoxia-Inducible Regulation of a Prodrug-Activating Enzyme for Tumor-Specific Gene Therapy

    Directory of Open Access Journals (Sweden)

    Toru Shibata

    2002-01-01

    Full Text Available Previous studies have suggested that tumor hypoxia could be exploited for cancer gene therapy. Using hypoxia-responsive elements derived from the human vascular endothelial growth factor gene, we have generated vectors expressing a bacterial nitroreductase. (20NTR gene that can activate the anticancer prodrug CB1954. Stable transfectants of human HT1080 tumor cells with hypoxia-inducible vectors were established with G418 selection. Hypoxic induction of NTR protein correlated with increased sensitivity to in vitro exposure of HT 1080 cells to the prodrug. Growth delay assays were performed with established tumor xenografts derived from the same cells to detect the in vivo efficacy of CB1954 conversion to its cytotoxic form. Significant antitumor effects were achieved with intraperitoneal injections of CB1954 both in tumors that express NTR constitutively or with a hypoxia-inducible promoter. In addition, respiration of 10% O2 increased tumor hypoxia in vivo and enhanced the antitumor effects. Taken together, these results demonstrate that hypoxia-inducible vectors may be useful for tumor-selective gene therapy, although the problem of delivery of the vector to the tumors, particularly to the hypoxic cells in the tumors, is not addressed by these studies.

  15. Preliminary design of the database and registration system for the national malignant tumor interventional therapy

    International Nuclear Information System (INIS)

    Hu Di; Zeng Jinjin; Wang Jianfeng; Zhai Renyou

    2010-01-01

    Objective: This research is one of the sub-researches of 'The comparative study of the standards of interventional therapies and the evaluation of the long-term and middle-term effects for common malignant tumors', which is one of the National Key Technologies R and D Program in the eleventh five-year plan. Based on the project,the authors need to establish an international standard in order to set up the national tumor interventional therapy database and registration system. Methods: By using the computing programs of downloading software, self-management and automatic integration, the program was written by the JAVA words. Results: The database and registration system for the national tumor interventional therapy was successfully set up, and it could complete both the simple and complex inquiries. The software worked well through the initial debugging. Conclusion: The national tumor interventional therapy database and registration system can not only precisely tell the popularizing rate of the interventional therapy nationwide, compare the results of different methods, provide the latest news concerning the interventional therapy, subsequently promote the academic exchanges between hospitals, but also help us get the information about the distribution of the interventional physicians, the consuming quantity and variety of the interventional materials, so the medical costs can be reduced. (authors)

  16. Deliberate total parathyroidectomy: a potentially novel therapy for tumor-induced hypophosphatemic osteomalacia.

    Science.gov (United States)

    Bhadada, Sanjay K; Palnitkar, Saroj; Qiu, Shijing; Parikh, Nayana; Talpos, Gary B; Rao, Sudhaker D

    2013-11-01

    Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic metabolic bone disorder that can be cured by removing or ablating the offending tumor. However, when the tumor cannot be localized, lifelong therapy with oral phosphate and calcitriol or cinacalcet with close monitoring is required. A 56-year-old man was diagnosed with TIO in 1990. Initial therapy consisted of oral phosphate and calcitriol with symptomatic and biochemical improvement and healing of osteomalacia. Eight years later, hypercalcemic hyperparathyroidism developed, requiring subtotal parathyroidectomy with a transient increase in serum phosphate and normalization of serum calcium and PTH. Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical therapy. A deliberate total parathyroidectomy produced a prompt rise in serum phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4 years of follow-up, despite continued very high serum fibroblast growth factor-23 levels throughout the 23-year follow-up. We report an unusual case of a TIO patient with long-term follow-up who developed recurrent hypercalcemic hyperparathyroidism on long-term oral phosphate therapy. Deliberate total parathyroidectomy normalized serum phosphate despite persistently elevated fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially novel therapy in some patients with TIO in whom medical therapy is not feasible or the tumor is unresectable.

  17. Lifestyle change as therapy for obesity

    Directory of Open Access Journals (Sweden)

    Adrian Vlad

    2009-12-01

    Full Text Available Lifestyle change (comprising adequate diet, physical activity, and behavior therapy represents the cornerstone of obesitytherapy. Dietary intervention consists primarily in reducing the energy content of the diet and secondarily in altering the relativemacronutrient composition. It is recommended to ingest low-calorie diets rather than very-low-calorie diets, because they aresafer and better accepted and provide at least similar long-term results. Low-fat diets have traditionally been prescribed forweight loss, because they facilitate energy restriction. Low-carbohydrate diets are helpful because they favor energy restriction,as well. Physical activity has favorable effects in obese patients: it prevents the decline in resting energy expenditure thataccompanies diet-induced weight loss, reduces the amount of free-fat mass lost, decreases the risk of developing type 2diabetes mellitus and of dying from cardiovascular disease, increases the rate of weight loss, and helps maintaining the resultson long term. Behavior therapy aims at altering eating and activity habits that promote obesity. It usually involves multiplestrategies, including stimulus control, self-monitoring, problem solving skills, cognitive restructuring, social support, andrelapse prevention. Many obese persons can achieve short-term weight loss by dieting alone. However, successful log-termresults are much more difficult to obtain and require a more complex strategy, including physical activity and behavior therapy.

  18. 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.

  19. [Anti-FGF23 antibody therapy for patients with tumor-induced osteomalacia].

    Science.gov (United States)

    Kinoshita, Yuka; Fukumoto, Seiji

    2014-08-01

    Tumor-induced osteomalacia (TIO) is a disease caused by fibroblast growth factor 23 (FGF23) secreted from the causative tumor. This disease is cured by complete surgical removal of the tumor. However, there are several difficult cases in which the responsible tumors cannot be found, are incompletely removed, or relapse after the surgery. Anti-FGF23 antibody is being studied as a novel therapy for FGF23-related hypophosphatemic diseases. The efficacy of anti-FGF23 antibodies were confirmed using a murine model of X-linked hypophosphatemic rickets (XLHR) , which is the most common heritable form of FGF23-related hypophosphatemic disease. In addition, results of phase I study of single injection of humanized anti-FGF23 antibody for adult patients with XLHR were recently published and the safety and effectiveness of this antibody was shown. This antibody therapy may be useful for patients with TIO with similar pathogenesis to that of XLHR.

  20. Evaluation of radioiodinated vesamicol analogs for sigma receptor imaging in tumor and radionuclide receptor therapy.

    Science.gov (United States)

    Ogawa, Kazuma; Shiba, Kazuhiro; Akhter, Nasima; Yoshimoto, Mitsuyoshi; Washiyama, Kohshin; Kinuya, Seigo; Kawai, Keiichi; Mori, Hirofumi

    2009-11-01

    It has been reported that sigma receptors are highly expressed in a variety of human tumors. In this study, we selected (+)-2-[4-(4-iodophenyl)piperidino] cyclohexanol [(+)-pIV] as a sigma receptor ligand and evaluated the potential of radioiodinated (+)-pIV for tumor imaging and therapy. (+)-[(125/131)I]pIV was prepared by an iododestannylation reaction under no-carrier-added conditions with radiochemical purity over 99% after HPLC purification. Biodistribution experiments were performed by the intravenous injection of (+)-[(125)I]pIV into mice bearing human prostate tumors (DU-145). Blocking studies were performed by intravenous injection of (+)-[(125)I]pIV mixed with an excess amount of unlabeled sigma ligand into DU-145 tumor-bearing mice. For therapeutic study, (+)-[(131)I]pIV was injected at a dose of 7.4 MBq followed by measurement of the tumor size. In biodistribution experiments, (+)-[(125)I]pIV showed high uptake and long residence in the tumor. High tumor to blood and muscle ratios were achieved because the radioactivity levels of blood and muscle were low. However, the accumulations of radioactivity in non-target tissues, such as liver and kidney, were high. The radioactivity in the non-target tissues slowly decreased over time. Co-injection of (+)-[(125)I]pIV with an excess amount of unlabeled sigma ligand resulted in a significant decrease in the tumor/blood ratio, indicating sigma receptor-mediated tumor uptake. In therapeutic study, tumor growth in mice treated with (+)-[(131)I]pIV was significantly inhibited compared to that of an untreated group. These results indicate that radioiodinated (+)-pIV has a high potential for sigma receptor imaging in tumor and radionuclide receptor therapy.

  1. New three-dimensional moving field radiation therapy for brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mitsuyama, Fuyuki; Kanno, Tetsuo; Nagata, Yutaka; Koga, Sukehiko [Fujita-Gakuen Health Univ., Toyoake, Aichi (Japan); Jain, V K

    1992-06-01

    A new modified rotation radiation method called 'three-dimensional moving field radiation therapy' is described. The new method uses rotation in many planes while maintaining the same isocenter to achieve a good spatial dose distribution. This delivers a high dose to tumors and spares the surrounding normal structures. This easy method can be carried out using the equipment for conventional rotation radiation therapy. The new method was superior to the one plane rotation radiation therapy using a physical phantom with film, a chemical phantom using the iodine-starch reaction, and a new biological model using tumor cells. Treatment of six brain tumors irradiated with total air doses of 50-60 Gy caused no hair loss or radiation necrosis. (author).

  2. Laser Therapy Inhibits Tumor Growth in Mice by Promoting Immune Surveillance and Vessel Normalization

    Directory of Open Access Journals (Sweden)

    Giulia Ottaviani

    2016-09-01

    Full Text Available Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression. This striking, unexpected result, was paralleled by the recruitment of immune cells, in particular T lymphocytes and dendritic cells, which secreted type I interferons. Laser light also reduced the number of highly angiogenic macrophages within the tumor mass and promoted vessel normalization, an emerging strategy to control tumor progression. Collectively, these results set photobiomodulation as a safety procedure in oncological patients and open the way to its innovative use for cancer therapy.

  3. In ovo method for evaluating the effect of nutritional therapies on tumor development, growth and vascularization

    OpenAIRE

    Dupertuis, Yves M.; Delie, Florence; Cohen, Marie; Pichard, Claude

    2015-01-01

    In the state of the art evaluation of nutritional therapy on tumor development, growth and vascularization requires tedious and expensive in vivo assays in which a significant number of animals undergo invasive treatments. Therefore, new alternative methods to avoid animal suffering and sacrifice are welcome. This review presents a rapid and low-cost method of experimental radio/chemotherapy in tumor xenografted chicken chorioallantoic membrane (CAM), which may contribute to implement the 3R ...

  4. Quality of Life After Stereotactic Body Radiation Therapy for Primary and Metastatic Liver Tumors

    International Nuclear Information System (INIS)

    Mendez Romero, Alejandra; Wunderink, Wouter; Os, Rob M. van; Nowak, Peter J.C.M.; Heijmen, Ben J.M.; Nuyttens, Joost J.; Brandwijk, Rene P.; Verhoef, Cornelis; IJzermans, Jan N.M.; Levendag, Peter C.

    2008-01-01

    Purpose: Stereotactic body radiation therapy (SBRT) provides a high local control rate for primary and metastatic liver tumors. The aim of this study is to assess the impact of this treatment on the patient's quality of life. This is the first report of quality of life associated with liver SBRT. Methods and Materials: From October 2002 to March 2007, a total of 28 patients not suitable for other local treatments and with Karnofsky performance status of at least 80% were entered in a Phase I-II study of SBRT for liver tumors. Quality of life was a secondary end point. Two generic quality of life instruments were investigated, EuroQol-5D (EQ-5D) and EuroQoL-Visual Analogue Scale (EQ-5D VAS), in addition to a disease-specific questionnaire, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ C-30). Points of measurement were directly before and 1, 3, and 6 months after treatment. Mean scores and SDs were calculated. Statistical analysis was performed using paired-samples t-test and Student t-test. Results: The calculated EQ-5D index, EQ-5D VAS and QLQ C-30 global health status showed that mean quality of life of the patient group was not significantly influenced by treatment with SBRT; if anything, a tendency toward improvement was found. Conclusions: Stereotactic body radiation therapy combines a high local control rate, by delivering a high dose per fraction, with no significant change in quality of life. Multicenter studies including larger numbers of patients are recommended and under development

  5. Radiation therapy for malignant tumors in patients 80 years of age or older

    International Nuclear Information System (INIS)

    Mitsuhashi, Norio; Niibe, Hideo; Hayakawa, Kazushige; Takahashi, Mitsuhiro; Nozaki, Miwako; Yamakawa, Michitaka

    1992-01-01

    We report here, results of investigation of changes in the condition of elderly patients, 80 years of age or older (EP-80), treated with radiation, and analysis of the results of radiotherapy to assess the value of radiotherapy in treating the elderly. Between 1970 and 1989, 294 EP-80 with various malignant tumors received radiation therapy at the Department of Radiology, Gunma University Hospital. The number of EP-80 treated has increased recently to about thirty per year, and their incidence among newly registered patients has also increased to over 5%. The 5-year cause specific survival rates for male and female were 14% and 32%, respectively. There was a significant difference between the survival rates for male and female (x 2 =11.89, p=0.00056) because of inclusion of a significant proportion of female patients with gynecological malignancies. The 5-year survival rate for patients in the curative radiotherapy group (CRG) was 30%, whereas no patient of the palliative radiotherapy group (PRG) has survived for 5 years (x 2 =90.23, p=0.00000). In the CRG, the survival rate for females was significantly higher than that for males (x 2 =11.48, p=0.00070). Thirty-one patients survived for 5 year. Head and neck cancer and uterine lervix cancer were the most common tumors in 5 year survivors. Age was not a significant prognostic factor in the elderly patients treated with radiation. It is considered that radiation therapy is as valuable in elderly patients as in the younger patient population. (author)

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

    Science.gov (United States)

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

    2017-11-15

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

  7. 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.

  8. Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

    Directory of Open Access Journals (Sweden)

    Rogerio M. Castilho

    2017-07-01

    Full Text Available Head and neck squamous carcinoma (HNSCC is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy. Epigenetic alterations occur in an unsystematic manner or as part of the aberrant transcriptional machinery, which promotes selective advantage to the tumor cells. Epigenetic modifications also contribute to cellular plasticity during tumor progression and to the formation of cancer stem cells (CSCs, a small subset of tumor cells with self-renewal ability. CSCs are involved in the development of intrinsic or acquired therapy resistance, and tumor recurrences or relapse. Therefore, the understanding and characterization of epigenetic modifications associated with head and neck carcinogenesis, and the prospective identification of epigenetic markers associated with CSCs, hold the promise for novel therapeutic strategies to fight tumors. In this review, we focus on the current knowledge on epigenetic modifications observed in HNSCC and emerging Epi-drugs capable of sensitizing HNSCC to therapy.

  9. Modulators of Response to Tumor Necrosis-Related Apoptosis-Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

    National Research Council Canada - National Science Library

    Behbakht, Kian

    2008-01-01

    .... More effective therapies are urgently needed. One of the most promising therapies in development for ovarian cancer is the use of either the Tumor Necrosis Factor-related Apoptosis Inducing Ligand (TRAIL...

  10. A Time-Delayed Mathematical Model for Tumor Growth with the Effect of a Periodic Therapy.

    Science.gov (United States)

    Xu, Shihe; Wei, Xiangqing; Zhang, Fangwei

    2016-01-01

    A time-delayed mathematical model for tumor growth with the effect of periodic therapy is studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a time delay in cell proliferation process. Sufficient conditions for the global stability of tumor free equilibrium are given. We also prove that if external concentration of nutrients is large the tumor will not disappear and the conditions under which there exist periodic solutions to the model are also determined. Results are illustrated by computer simulations.

  11. A Time-Delayed Mathematical Model for Tumor Growth with the Effect of a Periodic Therapy

    Directory of Open Access Journals (Sweden)

    Shihe Xu

    2016-01-01

    Full Text Available A time-delayed mathematical model for tumor growth with the effect of periodic therapy is studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a time delay in cell proliferation process. Sufficient conditions for the global stability of tumor free equilibrium are given. We also prove that if external concentration of nutrients is large the tumor will not disappear and the conditions under which there exist periodic solutions to the model are also determined. Results are illustrated by computer simulations.

  12. Quantitative Multi-Parametric Magnetic Resonance Imaging of Tumor Response to Photodynamic Therapy.

    Directory of Open Access Journals (Sweden)

    Tom J L Schreurs

    Full Text Available The aim of this study was to characterize response to photodynamic therapy (PDT in a mouse cancer model using a multi-parametric quantitative MRI protocol and to identify MR parameters as potential biomarkers for early assessment of treatment outcome.CT26.WT colon carcinoma tumors were grown subcutaneously in the hind limb of BALB/c mice. Therapy consisted of intravenous injection of the photosensitizer Bremachlorin, followed by 10 min laser illumination (200 mW/cm2 of the tumor 6 h post injection. MRI at 7 T was performed at baseline, directly after PDT, as well as at 24 h, and 72 h. Tumor relaxation time constants (T1 and T2 and apparent diffusion coefficient (ADC were quantified at each time point. Additionally, Gd-DOTA dynamic contrast-enhanced (DCE MRI was performed to estimate transfer constants (Ktrans and volume fractions of the extravascular extracellular space (ve using standard Tofts-Kermode tracer kinetic modeling. At the end of the experiment, tumor viability was characterized by histology using NADH-diaphorase staining.The therapy induced extensive cell death in the tumor and resulted in significant reduction in tumor growth, as compared to untreated controls. Tumor T1 and T2 relaxation times remained unchanged up to 24 h, but decreased at 72 h after treatment. Tumor ADC values significantly increased at 24 h and 72 h. DCE-MRI derived tracer kinetic parameters displayed an early response to the treatment. Directly after PDT complete vascular shutdown was observed in large parts of the tumors and reduced uptake (decreased Ktrans in remaining tumor tissue. At 24 h, contrast uptake in most tumors was essentially absent. Out of 5 animals that were monitored for 2 weeks after treatment, 3 had tumor recurrence, in locations that showed strong contrast uptake at 72 h.DCE-MRI is an effective tool for visualization of vascular effects directly after PDT. Endogenous contrast parameters T1, T2, and ADC, measured at 24 to 72 h after PDT, are

  13. Effectiveness of radiation therapy for metastatic spinal tumors producing neurologic impairment

    International Nuclear Information System (INIS)

    Yamamoto, Shuichiro; Nomoto, Satoshi; Imada, Hajime; Nakata, Hajime

    2002-01-01

    The purpose of this study was to evaluate the efficacy of radiation therapy (RT) for treating neurological impairment and improving quality of life (QOL) in patients with metastatic spinal tumors. From 1985 through 2001, 75 patients with metastatic spinal tumors were treated with RT. Neurologic status and Karnofsky performance status were assessed before and after RT. The rate of neurologic improvement was significantly higher in patients with radio-sensitive tumors (75%) than in patients with radio-resistant tumors (37%). Few patients with Karnofsky performance status less than 40% before RT had good QOL after RT. The response to RT did not differ significantly on the basis of duration of paralysis before RT. RT is useful for treating neurologic impairment caused by metastatic spinal tumors, particularly those that are radiosensitive. To have good QOL after RT, treatment should be started in the early stage of neurological impairment. (author)

  14. Boron neutron capture therapy for malignant brain tumor and future potential

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Hatanaka, Hiroshi.

    1994-01-01

    This paper presents therapeutic experience with boron neutron capture therapy (BNCT) for malignant brain tumors. Nine patients who survived for 10 years or more as of 1986 are given in a table. A review of the 9 patients concluded that physical dose of 15 Gy is required. In addition, the following factors are defined to be the most important: (1) to determine tumor size and depth as accurately as possible, (2) to measure neutron doses in the deepest site of the tumor during irradiation, (3) to measure the content of boron within the tumor, and to deliver neutron beams as deeply as possible. Finally, the importance of knowing RBE of alpha particles for tumor cells of the human brain is emphasized. (N.K.)

  15. Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy.

    Science.gov (United States)

    Denmeade, Samuel R; Mhaka, Annastasiah M; Rosen, D Marc; Brennen, W Nathaniel; Dalrymple, Susan; Dach, Ingrid; Olesen, Claus; Gurel, Bora; Demarzo, Angelo M; Wilding, George; Carducci, Michael A; Dionne, Craig A; Møller, Jesper V; Nissen, Poul; Christensen, S Brøgger; Isaacs, John T

    2012-06-27

    Heterogeneous expression of drug target proteins within tumor sites is a major mechanism of resistance to anticancer therapies. We describe a strategy to selectively inhibit, within tumor sites, the function of a critical intracellular protein, the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump, whose proper function is required by all cell types for viability. To achieve targeted inhibition, we took advantage of the unique expression of the carboxypeptidase prostate-specific membrane antigen (PSMA) by tumor endothelial cells within the microenvironment of solid tumors. We generated a prodrug, G202, consisting of a PSMA-specific peptide coupled to an analog of the potent SERCA pump inhibitor thapsigargin. G202 produced substantial tumor regression against a panel of human cancer xenografts in vivo at doses that were minimally toxic to the host. On the basis of these data, a phase 1 dose-escalation clinical trial has been initiated with G202 in patients with advanced cancer.

  16. Place of radiation therapy for the treatment of gynecologic and urologic tumors in 1994

    International Nuclear Information System (INIS)

    Maulard-Durdux, C.; Housset, M.

    1995-01-01

    External-beam radiation therapy and brachytherapy are currently used both as curative and as palliative therapy in patients with gynecologic and urologic tumors. Ionizing radiation plays a key role in the locoregional control of uterine and prostatic tumors, in particular in combination with surgery. External-beam radiation therapy in combination with concomitant radiosensitizing chemotherapy may allow conservation of the bladder in patients with infiltrating vesical tumors classically treated by cystectomy. It has beneficial effects on some of the most incapacitating complications of these cancers: its hemostatic effect is valuable in patients with vaginal bleeding or hematuria and it relieves the pain due to bone metastases, which are particularly common in prostatic cancer. Furthermore, use of high energy accelerators, development of better imaging techniques, and advances in dosimetry have substantially reduced the rate of delayed radiation-induced complications. Thus, external-beam radiation therapy and brachytherapy are important tools for the treatment of gynecologic and urologic tumors. A discussion is provided of the role of radiation therapy in the four most common types of gynecologic and urologic cancer: cancers of the prostate, bladder, uterine cervix, and uterine corpus. (authors). 52 refs., 2 tabs

  17. Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Yaozhong Hu

    2017-11-01

    Full Text Available The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma’s, monoclonal antibodies (mAbs have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue. By serendipity, a new kind of functional homodimeric antibody format was discovered in camelidae, known as heavy-chain antibodies (HCAbs. The cloning of the variable domain of HCAbs produces an attractive minimal-sized alternative for mAbs, referred to as VHH or nanobodies (Nbs. Apart from their dimensions in the single digit nanometer range, the unique characteristics of Nbs combine a high stability and solubility, low immunogenicity and excellent affinity and specificity against all possible targets including tumor markers. This stimulated the development of tumor-targeted therapeutic strategies. Some autonomous Nbs have been shown to act as antagonistic drugs, but more importantly, the targeting capacity of Nbs has been exploited to create drug delivery systems. Obviously, Nb-based targeted cancer therapy is mainly focused toward extracellular tumor markers, since the membrane barrier prevents antibodies to reach the most promising intracellular tumor markers. Potential strategies, such as lentiviral vectors and bacterial type 3 secretion system, are proposed to deliver target-specific Nbs into tumor cells and to block tumor markers intracellularly. Simultaneously, Nbs have also been employed for in vivo molecular imaging to diagnose diseased tissues and to monitor the treatment effects. Here, we review the state of the art and focus on recent developments with Nbs as

  18. Intrafractional Baseline Shift or Drift of Lung Tumor Motion During Gated Radiation Therapy With a Real-Time Tumor-Tracking System

    International Nuclear Information System (INIS)

    Takao, Seishin; Miyamoto, Naoki; Matsuura, Taeko; Onimaru, Rikiya; Katoh, Norio; Inoue, Tetsuya; Sutherland, Kenneth Lee; Suzuki, Ryusuke; Shirato, Hiroki; Shimizu, Shinichi

    2016-01-01

    Purpose: To investigate the frequency and amplitude of baseline shift or drift (shift/drift) of lung tumors in stereotactic body radiation therapy (SBRT), using a real-time tumor-tracking radiation therapy (RTRT) system. Methods and Materials: Sixty-eight patients with peripheral lung tumors were treated with SBRT using the RTRT system. One of the fiducial markers implanted near the tumor was used for the real-time monitoring of the intrafractional tumor motion every 0.033 seconds by the RTRT system. When baseline shift/drift is determined by the system, the position of the treatment couch is adjusted to compensate for the shift/drift. Therefore, the changes in the couch position correspond to the baseline shift/drift in the tumor motion. The frequency and amount of adjustment to the couch positions in the left-right (LR), cranio-caudal (CC), and antero-posterior (AP) directions have been analyzed for 335 fractions administered to 68 patients. Results: The average change in position of the treatment couch during the treatment time was 0.45 ± 2.23 mm (mean ± standard deviation), −1.65 ± 5.95 mm, and 1.50 ± 2.54 mm in the LR, CC, and AP directions, respectively. Overall the baseline shift/drift occurs toward the cranial and posterior directions. The incidence of baseline shift/drift exceeding 3 mm was 6.0%, 15.5%, 14.0%, and 42.1% for the LR, CC, AP, and for the square-root of sum of 3 directions, respectively, within 10 minutes of the start of treatment, and 23.0%, 37.6%, 32.5%, and 71.6% within 30 minutes. Conclusions: Real-time monitoring and frequent adjustments of the couch position and/or adding appropriate margins are suggested to be essential to compensate for possible underdosages due to baseline shift/drift in SBRT for lung cancers.

  19. The observation about the change of the body weight for tumor patients and the bearing tumor mice in radiotherapy

    International Nuclear Information System (INIS)

    Wu Dijun; Ju Yongjian; Ning Liyan; Wu Hong; Wang Gaoren; Gao Xuan; Tang Yahong

    2010-01-01

    Objective: To observe the change of the body weight for tumor patients and the bearing tumor mice in radiotherapy. Methods: For 63 tumor patients, the body weight (BW) were measured before and after radiotherapy respectively, and then the change of BW were compared and analyzed with that of 23 healthy volunteers at the median treatment period. Also 45 mice bearing human galactophore tumor cells SK-BR-3 were divided into irradiation and non-irradiation groups, and the change of BW for these two groups were measured and analyzed. Results: The average BW decreases in the irradiation groups' mice but increase in the non-irradiation groups' mice, and the change of BW in these two groups has the statistical significance respectively, also the difference between these two groups has the statistical significance. For the four groups' tumor patients including 63 tumor patients as a whole, the nasopharynx cancer, esophagus cancer and lung cancer, the average BW decreases, but only in nasopharynx cancer and lung cancer groups the statistical significance are found. And at the same period, the BW of healthy volunteers are maintained. Compared change of BW in the four tumor groups with that in the healthy volunteers respectively, except the esophagus cancer group, the statistical significance are found in the other three groups. Conclusion: For tumor patients,perhaps the BW will lose in the period of radiotherapy, so the effect of lose of BW must be cared about. (authors)

  20. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    OpenAIRE

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.; Bruns, Christiane J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associa...

  1. 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)

  2. Molecular imaging of tumor photoimmunotherapy: Evidence of photosensitized tumor necrosis and hemodynamic changes

    DEFF Research Database (Denmark)

    Kishimoto, Shun; Oshima, Nobu; Yamamoto, Kazutoshi

    2018-01-01

    Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode of cytotox......Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode...... of cytotoxicity based mainly on in vitro studies. To better understand the acute effects of NIR PIT, molecular imaging studies were performed to assess its cellular and vascular effects.In addition to in vitro studies for cytotoxicity of NIR PIT, the in vivo tumoricidal effects and hemodynamic changes induced....... Following NIR PIT, metabolic MRI using hyperpolarized fumarate showed the production of malate in EGFR-expressing A431 tumor xenografts, providing direct evidence for photosensitized tumor necrosis induced by NIR PIT. R2* mapping studies showed temporal changes in oxygenation, with an accompanying increase...

  3. Physical methods of treatment of complications of anti tumoral therapy

    International Nuclear Information System (INIS)

    Zhukovets, A.G.; Ulashchik, V.S.

    1998-01-01

    Numerous experimental and clinical materials about expediency of the use of physical methods for lowering of frequency and heaviness of complications of radial therapy are reviewed. One of such methods, possessing most expressed radioprotection ability, is low intensity laser radiation. Some of the authors demonstrated that use of this method move aside the time of appearance of early radial reactions. Preliminary local use of laser irradiation (λ = 510 nm) permits to avoid of development of epidermis disease and such radial reactions as ulcer and skin fibrosis in cancer patients after neutron-photon therapy. There are good results of application of ultraviolet irradiation in the region of action of ionizing radiation in the case of medical treatment of skin cancer. Low frequency magnetic field can reduce the expression of radial reactions

  4. Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

    International Nuclear Information System (INIS)

    Ohta, Kengo; Shimohira, Masashi; Sasaki, Shigeru; Iwata, Hiromitsu; Nishikawa, Hiroko; Ogino, Hiroyuki; Hara, Masaki; Hashizume, Takuya; Shibamoto, Yuta

    2015-01-01

    PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors

  5. Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Kengo, E-mail: yesterday.is.yesterday@gmail.com; Shimohira, Masashi, E-mail: mshimohira@gmail.com [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan); Sasaki, Shigeru, E-mail: ssasaki916@yahoo.co.jp; Iwata, Hiromitsu, E-mail: h-iwa-ncu@nifty.com; Nishikawa, Hiroko, E-mail: piroko1018@gmail.com; Ogino, Hiroyuki, E-mail: oginogio@gmail.com; Hara, Masaki, E-mail: mhara@med.nagoya-cu.ac.jp [Nagoya City West Medical Center, Department of Radiation Oncology, Nagoya Proton Therapy Center (Japan); Hashizume, Takuya, E-mail: tky300@gmail.com; Shibamoto, Yuta, E-mail: yshiba@med.nagoya-cu.ac.jp [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan)

    2015-10-15

    PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.

  6. Emergency surgery due to complications during molecular targeted therapy in advanced gastrointestinal stromal tumors (GIST)

    International Nuclear Information System (INIS)

    Rutkowski, P.; Nowecki, Z. I.; Dziewirski, W.; Ruka, W.; Siedlecki, J. A.; Grzesiakowska, U.

    2010-01-01

    Aim. The aim of the study was to assess the frequency and results of disease/treatment-related emergency operations during molecular targeted therapy of advanced gastrointestinal stromal tumors (GISTs). Methods. We analyzed emergency operations in patients with metastatic/inoperable GISTs treated with 1 st -line imatinib - IM (group I: 232 patients; median follow-up time 31 months) and 2 nd -line sunitinib - SU (group II: 43 patients; median follow-up 13 months; 35 patients in trial A6181036) enrolled into the Polish Clinical GIST Registry. Results. In group I 3 patients (1.3%) underwent emergency surgery due to disease/treatment related complications: one due to bleeding from a ruptured liver tumor (1 month after IM onset) and two due to bowel perforation on the tumor with subsequent intraperitoneal abscess (both 2 months after IM onset). IM was restarted 5-8 days after surgery and no complications in wound healing were observed. In group II 4 patients (9.5%) underwent emergency operations due to disease/treatment related complications: three due to bowel perforations on the tumor (2 days, 20 days and 10 months after SU onset; 1 subsequent death) and one due to intraperitoneal bleeding from ruptured, necrotic tumor (3.5 months after SU start). SU was restarted 12-18 days after surgery and no complications in wound healing were observed. Conclusions. Emergency operations associated with disease or therapy during imatinib treatment of advanced GISTs are rare. The frequency of emergency operations during sunitinib therapy is considered to be higher than during first line therapy with imatinib which may be associated with more advanced and more resistant disease or to the direct mechanism of sunitinib action, i.e. combining cytotoxic and antiangiogenic activity and thus leading to dramatic tumor response. Molecular targeted therapy in GISTs should always be conducted in cooperation with an experienced surgeon. (authors)

  7. Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy.

    Science.gov (United States)

    Zhang, Li; Takara, Kazuhiro; Yamakawa, Daishi; Kidoya, Hiroyasu; Takakura, Nobuyuki

    2016-01-01

    Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well-described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post-treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  8. Three-dimensional tumor spheroids for in vitro analysis of bacteria as gene delivery vectors in tumor therapy.

    Science.gov (United States)

    Osswald, Annika; Sun, Zhongke; Grimm, Verena; Ampem, Grace; Riegel, Karin; Westendorf, Astrid M; Sommergruber, Wolfgang; Otte, Kerstin; Dürre, Peter; Riedel, Christian U

    2015-12-12

    Several studies in animal models demonstrated that obligate and facultative anaerobic bacteria of the genera Bifidobacterium, Salmonella, or Clostridium specifically colonize solid tumors. Consequently, these and other bacteria are discussed as live vectors to deliver therapeutic genes to inhibit tumor growth. Therapeutic approaches for cancer treatment using anaerobic bacteria have been investigated in different mouse models. In the present study, solid three-dimensional (3D) multicellular tumor spheroids (MCTS) of the colorectal adenocarcinoma cell line HT-29 were generated and tested for their potential to study prodrug-converting enzyme therapies using bacterial vectors in vitro. HT-29 MCTS resembled solid tumors displaying all relevant features with an outer zone of proliferating cells and hypoxic and apoptotic regions in the core. Upon incubation with HT-29 MCTS, Bifidobacterium bifidum S17 and Salmonella typhimurium YB1 selectively localized, survived and replicated in hypoxic areas inside MCTS. Furthermore, spores of the obligate anaerobe Clostridium sporogenes germinated in these hypoxic areas. To further evaluate the potential of MCTS to investigate therapeutic approaches using bacteria as gene delivery vectors, recombinant bifidobacteria expressing prodrug-converting enzymes were used. Expression of a secreted cytosine deaminase in combination with 5-fluorocytosine had no effect on growth of MCTS due to an intrinsic resistance of HT-29 cells to 5-fluorouracil, i.e. the converted drug. However, a combination of the prodrug CB1954 and a strain expressing a secreted chromate reductase effectively inhibited MCTS growth. Collectively, the presented results indicate that MCTS are a suitable and reliable model to investigate live bacteria as gene delivery vectors for cancer therapy in vitro.

  9. Experimental study of chemical embolus therapy combined with radiotherapy for VX2 bone tumors

    International Nuclear Information System (INIS)

    Yamaguchi, Hiroshi; Mochizuki, Kazuo; Ishii, Yoshiaki

    2000-01-01

    We conducted an experimental study, using a combination of coarse crystal cisplatin and radiotherapy for bone tumors, to evaluate the possibility of the clinical application of chemical embolus therapy in the field of orthopedic surgery. Experimental femoral bone tumors were produced, in rabbits, using VX2 carcinoma. The rabbits were allocated to five groups: untreated control, embolus, chemical embolus, irradiation alone, and chemical embolus and irradiation combination. These therapies were evaluated comparatively, in terms of local antitumor effects (including body weight, X-ray findings, angiography, and histopathology) and in terms of inhibition of pulmonary metastasis. Local antitumor effects, as evaluated by all parameters, except for body weight, were significantly greater for the chemical and irradiation combination group than for the chemical embolus, irradiation alone, untreated control, and embolus groups. There was no significant difference in the inhibition of pulmonary metastasis among the chemical embolus and irradiation combination, chemical embolus, and irradiation alone groups. These findings demonstrated the synergistic effect of the combination of chemical embolus therapy and radiotherapy. In this study, however, no significant difference was found between the chemical embolus therapy alone and the combination therapy groups in the inhibitory effect on pulmonary tumor metastasis, suggesting the need to conduct combination therapy repeatedly in the clinical setting. (author)

  10. Connexin 43 Gene Therapy Delivered by Polymer-Modified Salmonella in Murine Tumor Models

    Directory of Open Access Journals (Sweden)

    Wei-Kuang Wang

    2014-04-01

    Full Text Available The use of preferentially tumor-targeting bacteria as vectors is one of the most innovative approaches for the treatment of cancer. This method is based on the observation that some obligate or facultative anaerobic bacteria are capable of selectively multiplying in tumors and inhibiting their growth. Previously, we found that the tumor-targeting efficiency of Salmonella could be modulated by modifying the immune response to these bacteria by coating them with poly(allylamine hydrochloride (PAH, and these organisms are designated PAH-S.C. (S. choleraesuis. PAH can provide a useful platform for the chemical modification of Salmonella, perhaps by allowing a therapeutic gene to bind to tumor-targeting Salmonella. This study aimed to investigate the benefits of the use of PAH-S.C. for gene delivery. To evaluate this modulation, the invasion activity and gene transfer of DNA-PAH-S.C. were measured in vitro and in vivo. Treatment with PAH-S.C. carrying a tumor suppressor gene (connexin 43 resulted in inhibition of tumor growth, which suggested that tumor-targeted gene therapy using PAH-S.C. carrying a therapeutic gene could exert antitumor activities. This technique represents a promising strategy for the treatment of tumors.

  11. Nanoparticles and synchrotron light for brain tumors therapy

    International Nuclear Information System (INIS)

    Taupin, Florence

    2013-01-01

    Gliomas treatment is still a serious challenge in medicine. Available treatments are mainly palliative and patients' survival is increased by a few months only. An original radiotherapy technique consists in increasing the dose delivered to the tumor by loading it with high Z atoms before an irradiation with low energy X-rays (50-100 keV). Preclinical studies have been conducted using iodine contrast agent (CA) (Z=53) and 50 keV X-rays. The increase of the animals' survival leads today to the beginning of clinical trials (phases I and II) at the medical beamline of the European synchrotron, where the available monochromatic and intense photons beam is well suited for this treatment. The use of intravenously injected CA is however insufficient for curing rat's bearing glioma. Indeed, the contrast agent's accumulation is limited by the presence of the BBB and it remains extracellular. Metallic nanoparticles (NPs) appear interesting for improving the treatment efficacy. During this work, three different types of NPs have been studied: GdNPs (3 nm), AuNPs (13 nm) and PtNPs (6 nm). Their toxicity and internalization have been evaluated in vitro on F98 rodent glioma cells. Cells' survival has also been measured after different irradiation conditions in presence of these NPs and with monochromatic photons beams. Several mechanisms implicated in the treatment have been highlighted by the study of the cells' response dependence to the incident particles energy and to the sub cellular NPs distribution during irradiation. For identical concentrations, NPs were more efficient in cells killing than CA, illustrating their microdosimetric potential. The effect was also preferential for low energy X-rays, indicating that photoactivation of heavy atoms plays a role in the cells' death. GdNPs and PtNPs have also lead to an effect in combination to high energy photons (1.25 MeV), indicating that another mechanism may also increase the cell

  12. Research progress in nanographene oxide with tumor imaging and therapy

    Directory of Open Access Journals (Sweden)

    YOU Peihong

    2015-04-01

    Full Text Available Nanographene oxide,one of graphene oxide derivatives and a novel two-dimensional carbon nanomaterial,has become a popular research topic in nanomedicine due to its unique properties such as ultra-high surface-to-volume ratio and great photo-thermal effect.It contains a large amount of reactive chemical groups,including carboxy group,carbonyl group,hydroxyl group and epoxy group,which enable its easy biological and chemical functionalization and excellent biocompatibility.Therefore,it has potential applications in biomedical field.This paper briefly describes the preparation and functionalization of nanographeme oxide,and then mainly focuses on its application studies in the biomedical field,including in vitro and in vivo toxicity tests and advanced research progress of tumor imaging and treatment.

  13. 3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration.

    Science.gov (United States)

    Ma, Hongshi; Luo, Jian; Sun, Zhe; Xia, Lunguo; Shi, Mengchao; Liu, Mingyao; Chang, Jiang; Wu, Chengtie

    2016-12-01

    Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Treatment outcome of thymic epithelial tumor: prognostic factors and optimal postoperative radiation therapy

    International Nuclear Information System (INIS)

    Oh, Dong Ryul; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhin Gook; Shim, Young Mog; Han, Jung Ho

    2005-01-01

    This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious incomplete resection or positive resection margin or Masaoka stage II ∼ IV or WHO tumor type B2 ∼ C. PORT performed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. The overall survival rate at 5 years was 87.3%. Age (more than 60 years 77.8%, less than 60 years 91.1%; ρ = 0.03), Masaoka stage (I 92.2%, II 95.4%, III 82.1%, IV 67.5%; ρ = 0.001), WHO tumor type (A-B1 96.0%, B2-C 82.3%; ρ = 0.001), Extent of resection (R0 resection 92.3%, R1 or 2 resection 72.6%; ρ = 0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection ) and PORT to primary tumor bed. Mediastinal recurrence was observed in only one patients. There were no recurrence within irradiation field. WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura-or pericardium-based recurrence, further study of effective chemotherapy should be investigated

  16. A review of endocrine late effects in children after brain tumor therapy

    International Nuclear Information System (INIS)

    Marx, M.; Langer, T.; Beck, J.D.; Doerr, H.G.

    1999-01-01

    Background: Advances in the therapy of malignant brain tumors in children have led to a significant improvement in survival rates over the last few decades. As a result, the recognition and treatment of late effects have become more important. In addition to secondary tumors and deficiencies in cognitive and intellectual skills, the resulting endocrine disturbances play an important role. Method: Own data and literature review. Results: Deviations from the normal growth hormone secretion are usually recognized first and are most common, and have already been observed after conventional whole brain irradiation with 18 G. With some delay, other hypothalamopituitary deficiencies may occur, including panhypopituitarism. Puberty may come too early or too late or may not appear at all. Girls in particular, frequently experience an early and rapid pubertal development after brain tumor therapy, which may lead to further reduction in height due to an accelerated bone maturation. Functional disturbances of the thyroid and adrenal glands due to hypothalamic or pituitary deficiency are less common, and usually seen only after a radiation dose of over 40 Gy. Conclusion: Survivors of childhood brain tumors must be considered as long-term survivors, in whom the first therapy-induced long-term side effects appear almost immediately after the end of therapy. Maximum quality of life for the individual patient can only be achieved by long-term care and close cooperation of specialists in the different medical disciplines involved. (orig.) [de

  17. Effective experimental tumor therapy with targeted polymer drug delivery systems based on HPMA copolymers.

    Czech Academy of Sciences Publication Activity Database

    Šírová, Milada; Horková, Veronika; Sivák, Ladislav; Etrych, Tomáš; Říhová, Blanka; Studenovský, Martin

    SI (2016), s. 24-24 ISSN 0014-2980. [3rd Meeting of Middle – European Societies for Immunology and Allergology. 01.12.2016-03.12.2016, Budapest ] R&D Projects: GA ČR(CZ) GA14-12742S Institutional support: RVO:61388971 ; RVO:61389013 Keywords : Tumor therapy * polymer drug * HPMA copolymers Subject RIV: EE - Microbiology, Virology

  18. Phenotype switching : tumor cell plasticity as a resistance mechanism and target for therapy

    NARCIS (Netherlands)

    Kemper, K.; de Goeje, P.L.; Peeper, D.S.; van Amerongen, R.

    2014-01-01

    Mutations in BRAF are present in the majority of patients with melanoma, rendering these tumors sensitive to targeted therapy with BRAF and MEK inhibitors. Unfortunately, resistance almost invariably develops. Recently, a phenomenon called "phenotype switching" has been identified as an escape

  19. A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy

    Science.gov (United States)

    Liu, Yang; Ashton, Jeffrey R.; Moding, Everett J.; Yuan, Hsiangkuo; Register, Janna K.; Fales, Andrew M.; Choi, Jaeyeon; Whitley, Melodi J.; Zhao, Xiaoguang; Qi, Yi; Ma, Yan; Vaidyanathan, Ganesan; Zalutsky, Michael R.; Kirsch, David G.; Badea, Cristian T.; Vo-Dinh, Tuan

    2015-01-01

    Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy. PMID:26155311

  20. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

    2015-01-01

    stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  1. Boron neutron capture therapy (BNCT) using fast neutrons: Effects in two human tumor cell lines

    International Nuclear Information System (INIS)

    Sauerwein, W.; Ziegler, W.; Szypniewski, H.; Streffer, C.

    1990-01-01

    The results demonstrate that the effect of fast neutrons on cell survival in cell culture can be enhanced by boron neutron capture reaction. Even with lower enhancement ratios, the concept of NCT assisted fast neutron therapy may successfully be applied for tumor treatment with the Essen cyclotron. (orig.)

  2. Visual outcome after fractionated stereotactic radiation therapy of benign anterior skull base tumors

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Wiencke, Anne Katrine; Munck af Rosenschold, Per

    2014-01-01

    To determine visual outcome including the occurrence of radiation induced optic neuropathy (RION) as well as tumor control after fractionated stereotactic radiation therapy (FSRT) of benign anterior skull base meningiomas or pituitary adenomas. Thirty-nine patients treated with FSRT for anterior...

  3. Role of stem cells in tumor initiation, metastasis formation and their use in cancer therapy

    International Nuclear Information System (INIS)

    Altaner, C.; Altanerova, V.

    2010-01-01

    This review considers recent advances in the stem cell field focusing on the challenges and opportunities for their use in clinical practice. Various kinds of stem cells and their roles in the human organism are in the review described. Attention is given to the role of mesenchymal stem cells as a potential tool in regenerative medicine. The origin and consequences of existence of tumor-initiating cells known as cancer stem cells is discussed also in context of metastasis formation. It seems that tumor-initiating cells might be responsible for resistance to many conventional cancer therapies, which might explain the limitations of these therapeutic modalities. Furthermore, the review focuses to tumor homing property of adult mesenchymal (stromal) stem cells. The feasibility of mesenchymal stem cells isolation from human adipose tissue, their genetic modifications with suicide genes together with ability to find tumor in the organism make them an attractive vehicle for cancer therapy without systemic toxicity. Published achievements from our laboratory in stem cell-based gene cancer therapy are shortly summarized. Generally, it is believed that the stem cell therapies might be ideal future treatment modality for inherited, degenerative diseases and in curing human malignancies as well. (author)

  4. Does performance status influence the outcome of Nd:YAG laser therapy of proximal esophageal tumors?

    NARCIS (Netherlands)

    Alexander, G. L.; Wang, K. K.; Ahlquist, D. A.; Viggiano, T. R.; Gostout, C. J.; Balm, R.

    1994-01-01

    The value of endoscopic palliative therapy for malignant obstruction in the proximal esophagus has been questioned. To assess the importance of pre-treatment performance status on treatment outcome, we reviewed the records of patients with tumors of the proximal esophagus undergoing endoscopic laser

  5. Imaging Tumor Variation in Response to Photodynamic Therapy in Pancreatic Cancer Xenograft Models

    International Nuclear Information System (INIS)

    Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; O'Hara, Julia A.; Hoopes, P. Jack; Pereira, Stephen P.; Hasan, Tayyaba; Pogue, Brian W.

    2010-01-01

    Purpose: A treatment monitoring study investigated the differential effects of orthotopic pancreatic cancer models in response to interstitial photodynamic therapy (PDT), and the validity of using magnetic resonance imaging as a surrogate measure of response was assessed. Methods and Materials: Different orthotopic pancreatic cancer xenograft models (AsPC-1 and Panc-1) were used to represent the range of pathophysiology observed in human beings. Identical dose escalation studies (10, 20, and 40J/cm) using interstitial verteporfin PDT were performed, and magnetic resonance imaging with T2-weighted and T1-weighted contrast were used to monitor the total tumor volume and the vascular perfusion volume, respectively. Results: There was a significant amount of necrosis in the slower-growing Panc-1 tumor using high light dose, although complete necrosis was not observed. Lower doses were required for the same level of tumor kill in the faster-growing AsPC-1 cell line. Conclusions: The tumor growth rate and vascular pattern of the tumor affect the optimal PDT treatment regimen, with faster-growing tumors being relatively easier to treat. This highlights the fact that therapy in human beings shows a heterogeneous range of outcomes, and suggests a need for careful individualized treatment outcomes assessment in clinical work.

  6. Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Olga A. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); Anderson, Robin L. [The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Russell, Prudence A. [Department of Anatomical Pathology, St. Vincent Hospital, Fitzroy, VIC (Australia); Ashley Cox, R. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Ivashkevich, Alesia [Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Laboratory of DNA Repair and Genomics, Centre for Innate Immunity and Infectious Disease, Monash Institute for Medical Research, Monash University, Clayton, VIC (Australia); Swierczak, Agnieszka; Doherty, Judy P. [Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Jacobs, Daphne H.M. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Smith, Jai [Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Siva, Shankar; Daly, Patricia E. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Ball, David L. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); and others

    2014-02-01

    Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.

  7. Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

    International Nuclear Information System (INIS)

    Martin, Olga A.; Anderson, Robin L.; Russell, Prudence A.; Ashley Cox, R.; Ivashkevich, Alesia; Swierczak, Agnieszka; Doherty, Judy P.; Jacobs, Daphne H.M.; Smith, Jai; Siva, Shankar; Daly, Patricia E.; Ball, David L.

    2014-01-01

    Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies

  8. Achievements and challenges of adoptive T cell therapy with tumor-infiltrating or blood-derived lymphocytes for metastatic melanoma

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Verdegaal, Els M

    2014-01-01

    Adoptive cell therapy (ACT) based on autologous T cell derived either from tumor as tumor-infiltrating lymphocytes (TILs) or from peripheral blood is developing as a key area of future personalized cancer therapy. TIL-based ACT is defined as the infusion of T cells harvested from autologous fresh...

  9. The potential for tumor suppressor gene therapy in head and neck cancer.

    Science.gov (United States)

    Birkeland, Andrew C; Ludwig, Megan L; Spector, Matthew E; Brenner, J Chad

    2016-01-01

    Head and neck squamous cell carcinoma remains a highly morbid and fatal disease. Importantly, genomic sequencing of head and neck cancers has identified frequent mutations in tumor suppressor genes. While targeted therapeutics increasingly are being investigated in head and neck cancer, the majority of these agents are against overactive/overexpressed oncogenes. Therapy to restore lost tumor suppressor gene function remains a key and under-addressed niche in trials for head and neck cancer. Recent advances in gene editing have captured the interest of both the scientific community and the public. As our technology for gene editing and gene expression modulation improves, addressing lost tumor suppressor gene function in head and neck cancers is becoming a reality. This review will summarize new techniques, challenges to implementation, future directions, and ethical ramifications of gene therapy in head and neck cancer.

  10. Case of false positive scanning observed after radiation therapy for orbital tumor

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, H [Gifu Prefectural Tajimi Hospital (Japan); Nakamura, K; Maeda, S; Watanabe, R; Miyajima, T

    1978-12-01

    A report was made of 56-year-old female patient of abducensparesis. In the early stage the cause remained undetermined with nothing abnormal noted in scintigraphy. Diplopia disappeared once, but right, exophalmus relapsed. In gammaencepharography, a hot spot was noted in the orbita, sinus ethmoidalis and sirus sphenoidalis. In an operation, squamous cell carcinoma was removed and radiation therapy was performed (total dose of 3520 r) and, three months later a scintigraphy disclosed a high spot of /sup 203/Hg uptake ratio in the right orbita and its lower portions. The biopsy of these portions disclosed a necrotic tissue instead of a tumor. In scintigraphy after radiation therapy against the tumor, it was reported that a positive scintigraphy was present because of the vascular trouble of said portions, although the tumor had disappeared. Attention should be given as well as an opinion of high density together with the examination by CT, especially as to enhancement.

  11. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

    2015-03-15

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

  12. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    International Nuclear Information System (INIS)

    Bradshaw, Tyler J.; Bowen, Stephen R.; Deveau, Michael A.; Kubicek, Lyndsay; White, Pamela; Bentzen, Søren M.; Chappell, Richard J.; Forrest, Lisa J.; Jeraj, Robert

    2015-01-01

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV max ; SUV mean ) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R 2 . Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV mean (P=.018), and midtreatment FLT SUV max (P=.006). Large decreases in FLT SUV mean from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV max (P=.022) in combination with large FLT response from

  13. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associated with the utility of MSC-based therapy such as biosafety, immunoprivilege, transfection methods, and distribution in the host. PMID:22530882

  14. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others)

    2002-06-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  15. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    International Nuclear Information System (INIS)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko

    2002-01-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 μg corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  16. Volumetric Modulated Arc Therapy (VMAT) Treatment Planning for Superficial Tumors

    International Nuclear Information System (INIS)

    Zacarias, Albert S.; Brown, Mellonie F.; Mills, Michael D.

    2010-01-01

    The physician's planning objective is often a uniform dose distribution throughout the planning target volume (PTV), including superficial PTVs on or near the surface of a patient's body. Varian's Eclipse treatment planning system uses a progressive resolution optimizer (PRO), version 8.2.23, for RapidArc dynamic multileaf collimator volumetric modulated arc therapy planning. Because the PRO is a fast optimizer, optimization convergence errors (OCEs) produce dose nonuniformity in the superficial area of the PTV. We present a postsurgical cranial case demonstrating the recursive method our clinic uses to produce RapidArc treatment plans. The initial RapidArc treatment plan generated using one 360 o arc resulted in substantial dose nonuniformity in the superficial section of the PTV. We demonstrate the use of multiple arcs to produce improved dose uniformity in this region. We also compare the results of this superficial dose compensation method to the results of a recursive method of dose correction that we developed in-house to correct optimization convergence errors in static intensity-modulated radiation therapy treatment plans. The results show that up to 4 arcs may be necessary to provide uniform dose to the surface of the PTV with the current version of the PRO.

  17. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children' s Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children' s Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children' s Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

  18. Daily Tracking of Glioblastoma Resection Cavity, Cerebral Edema, and Tumor Volume with MRI-Guided Radiation Therapy.

    Science.gov (United States)

    Mehta, Shahil; Gajjar, Shefali R; Padgett, Kyle R; Asher, David; Stoyanova, Radka; Ford, John C; Mellon, Eric A

    2018-03-19

    Radiation therapy (RT) plays a critical role in the treatment of glioblastoma. Studies of brain imaging during RT for glioblastoma have demonstrated changes in the brain during RT. However, frequent or daily utilization of standalone magnetic resonance imaging (MRI) scans during RT have limited feasibility. The recent release of the tri-cobalt-60 MRI-guided RT (MR-IGRT) device (ViewRay MRIdian, Cleveland, OH) allows for daily brain MRI for the RT setup. Daily MRI of three postoperative patients undergoing RT and temozolomide for glioblastoma over a six-week course allowed for the identification of changes to the cavity, edema, and visible tumor on a daily basis. The volumes and dimensions of the resection cavities, edema, and T2-hyperintense tumor were measured. A general trend of daily decreases in cavity measurements was observed in all patients. For the one patient with edema, a trend of daily increases followed by a trend of daily decreases were observed. These results suggest that daily MRI could be used for onboard resimulation and adaptive RT for future fluctuations in the sizes of brain tumors, cavities, or cystic components. This could improve tumor targeting and reduce RT of healthy brain tissue.

  19. Evaluation of the breath-hold approach in proton therapy of lung tumors

    DEFF Research Database (Denmark)

    Gorgisyan, Jenny

    Proton therapy has the potential to improve the treatment effect as compared to conventional radiation therapy for lung cancer patients. However, the proton therapy delivery is prone to uncertainties caused by anatomical changes and motion during the treatment and between the treatment fractions ...

  20. Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

    Directory of Open Access Journals (Sweden)

    Malini Olivo

    2010-05-01

    Full Text Available Photodynamic therapy (PDT has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS, which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS, that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

  1. Segmentation of tumor ultrasound image in HIFU therapy based on texture and boundary encoding

    International Nuclear Information System (INIS)

    Zhang, Dong; Xu, Menglong; Quan, Long; Yang, Yan; Qin, Qianqing; Zhu, Wenbin

    2015-01-01

    It is crucial in high intensity focused ultrasound (HIFU) therapy to detect the tumor precisely with less manual intervention for enhancing the therapy efficiency. Ultrasound image segmentation becomes a difficult task due to signal attenuation, speckle effect and shadows. This paper presents an unsupervised approach based on texture and boundary encoding customized for ultrasound image segmentation in HIFU therapy. The approach oversegments the ultrasound image into some small regions, which are merged by using the principle of minimum description length (MDL) afterwards. Small regions belonging to the same tumor are clustered as they preserve similar texture features. The mergence is completed by obtaining the shortest coding length from encoding textures and boundaries of these regions in the clustering process. The tumor region is finally selected from merged regions by a proposed algorithm without manual interaction. The performance of the method is tested on 50 uterine fibroid ultrasound images from HIFU guiding transducers. The segmentations are compared with manual delineations to verify its feasibility. The quantitative evaluation with HIFU images shows that the mean true positive of the approach is 93.53%, the mean false positive is 4.06%, the mean similarity is 89.92%, the mean norm Hausdorff distance is 3.62% and the mean norm maximum average distance is 0.57%. The experiments validate that the proposed method can achieve favorable segmentation without manual initialization and effectively handle the poor quality of the ultrasound guidance image in HIFU therapy, which indicates that the approach is applicable in HIFU therapy. (paper)

  2. Summary of the primer on tumor immunology and the biological therapy of cancer

    Directory of Open Access Journals (Sweden)

    Margolin Kim

    2009-01-01

    Full Text Available Abstract The International Society for Biological Therapy of Cancer (iSBTc is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this program includes investigators from academic, regulatory, and biopharmaceutical venues. The program goal is to enable the attendees to learn the current status and the most recent advances in biologic therapies, and to leverage this knowledge towards the improvement of cancer therapy. The 2008 immunologic primer course was held on October 30 at the 23rd Annual meeting of iSBTc in San Diego, CA. Nine internationally renowned investigators gave excellent presentations on different topics. The topics covered in this primer included: (1 cytokines in cancer immunology; (2 anti-angiogenic therapy; (3 end stage: immune killing of tumors; (4 blocking T cell checkpoints; (5 approach to identification and therapeutic exploitation of tumor antigens; (6 T regulatory cells; (7 adoptive T cell therapy; (8 immune monitoring of cancer immunotherapy; and (9 immune adjuvants. We summarized the topics in this primer for public education. The related topic slides and schedule can be accessed online http://www.isbtc.org/meetings/am08/primer08.

  3. Metabolic imaging of tumor for diagnosis and response for therapy

    Science.gov (United States)

    Zagaynova, Elena; Shirmanova, Marina; Lukina, Maria; Dudenkova, Varvara; Ignatova, Nadezgda; Elagin, Vadim; Shlivko, Irena; Scheslavsky, Vladislav; Orlinskay, Natalia

    2018-02-01

    Nonlinear optical microscopy combined with fluorescence lifetime imaging is a non-invasive imaging technique, based on the study of fluorescence decay times of naturally occurring fluorescent molecules, enabling a noninvasive investigation of the biological tissue with subcellular resolution. Cancer exhibits altered cellular metabolism, which affects the autofluorescence of metabolic cofactors NAD(P)H and FAD. In this study features of tumor metabolism in different systems of organization (from cell culture to patient lesion) was showed. The observed differences in the relative contributions of free NAD(P)H and FAD testify to an increased a glycolytic metabolism in cancer cells compare to fibroblasts. In 3D spheroids, the cells of the proliferating zone had greater a1 and lower tm values than the cells of the quiescent zone, which likely is a consequence of their higher glycolytic rate. During the growth of colorectal cancer in the experimental mouse model, the contribution of the free component of NAD(P)H was increased. Dysplastic nevus and melanoma is characterized by raised contribution of free NADH compare to healthy skin. Therefore, melanoma cells had very short value of τ1.

  4. Physics of radiation therapy of head and neck tumors

    International Nuclear Information System (INIS)

    Almond, P.R.

    1987-01-01

    Radiotherapy treatment of head and neck cancers probably requires more individual planning than for any other cancer site because of the large number of variables that exist. The fact that tumors may be superficial or relatively deep-seated, the complex shape of the head and neck region, the presence of significant inhomogeneities such as bone and air spaces, and the need to spare critical structures such as the eyes or central nervous system all add to the need for careful considerations of the physical parameters involved in radiotherapy. In addition, the high mobility of the head allows it to assume a wide variety of positions so that techniques have had to be developed for careful simulation, repositioning, and immobilization during treatment. In the head and neck region shaping of the beam becomes important, and therefore, blocked fields, compensators, or wedges are often used. Although the specific radiotherapy techniques for each site of head and neck cancer are described in the various chapters of this book, a general description of the various types of radiation beams, radioactive sources, beam modifiers, treatment planning techniques, and treatment implementation is given in this chapter. The discussion is divided into three main categories: (1) external beam, (2) brachytherapy, and (3) simulation and immobilization

  5. Biological models in vivo for boron neutronic capture studies as tumors therapy

    International Nuclear Information System (INIS)

    Kreimann, Erica L.; Dagrosa, Maria A.; Schwint, Amanda E.; Itoiz, Maria E.; Pisarev, Mario A.; Farias, Silvia S.; Garavaglia, Ricardo N.; Batistoni, Daniel A.

    1999-01-01

    The use of experimental models for Boron Neutronic Capture studies as Tumors Therapy have as two main objectives: 1) To contribute to the basic knowledge of the biological mechanisms involved to increase the method therapeutical advantage, and 2) To explore the possible application of this therapeutic method to other pathologies. In this frame it was studied the carcinogenesis model of hamster cheek pouch, a type of human buccal cancer. Biodistribution studies of boron compound were performed in tumor, blood and in different precancerous and normal tissues as well as BNCT studies. Results validated this method for BNCT studies and show the capacity of the oral mucosa tumors of selectively concentrate the boron compound, showing a deleterious clear effect on the tumor after 24 hours with BNCT treatment. (author)

  6. The use of amino acid PET and conventional MRI for monitoring of brain tumor therapy

    DEFF Research Database (Denmark)

    Galldiks, Norbert; Law, Ian; Pope, Whitney B

    2017-01-01

    Routine diagnostics and treatment monitoring of brain tumors is usually based on contrast-enhanced MRI. However, the capacity of conventional MRI to differentiate tumor tissue from posttherapeutic effects following neurosurgical resection, chemoradiation, alkylating chemotherapy, radiosurgery, and......),O-(2-[18F]fluoroethyl)-l-tyrosine (FET) and 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (FDOPA) and summarizes investigations regarding monitoring of brain tumor therapy......./or immunotherapy may be limited. Metabolic imaging using PET can provide relevant additional information on tumor metabolism, which allows for more accurate diagnostics especially in clinically equivocal situations. This review article focuses predominantly on the amino acid PET tracers11C-methyl-l-methionine (MET...

  7. Cell Death Conversion under Hypoxic Condition in Tumor Development and Therapy

    Directory of Open Access Journals (Sweden)

    Yu Qiu

    2015-10-01

    Full Text Available Hypoxia, which is common during tumor progression, plays important roles in tumor biology. Failure in cell death in response to hypoxia contributes to progression and metastasis of tumors. On the one hand, the metabolic and oxidative stress following hypoxia could lead to cell death by triggering signal cascades, like LKB1/AMPK, PI3K/AKT/mTOR, and altering the levels of effective components, such as the Bcl-2 family, Atg and p62. On the other hand, hypoxia-induced autophagy can serve as a mechanism to turn over nutrients, so as to mitigate the adverse condition and then avoid cell death potentially. Due to the effective role of hypoxia, this review focuses on the crosstalk in cell death under hypoxia in tumor progression. Additionally, the illumination of cell death in hypoxia could shed light on the clinical applications of cell death targeted therapy.

  8. Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

    Science.gov (United States)

    da Rocha, E L; Porto, L M; Rambo, C R

    2014-01-01

    Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

  9. Subacute brain atrophy induced by radiation therapy to the malignant brain tumors

    International Nuclear Information System (INIS)

    Asai, Akio; Matsutani, Masao; Takakura, Kintomo.

    1987-01-01

    In order to analyze brain atrophy after radiation therapy to the brain tumors, we calculated a CSF-cranial volume ratio on CT scan as an index of brain atrophy, and estimated dementia-score by Hasegawa's method in 91 post-irradiated patients with malignant brain tumors. Radiation-induced brain atrophy was observed in 51 out of 91 patients (56 %) and dementia in 23 out of 47 patients (49 %). These two conditions were closely related, and observed significantly more often in aged and whole-brain-irradiated patients. As radiation-induced brain atrophy accompanied by dementia appeared 2 - 3 months after the completion of radiation therapy, it should be regarded as a subacute brain injury caused by radiation therapy. (author)

  10. Dual antibody therapy to harness the innate anti-tumor immune response to enhance antibody targeting of tumors.

    Science.gov (United States)

    Chester, Cariad; Marabelle, Aurelien; Houot, Roch; Kohrt, Holbrook E

    2015-04-01

    Cancer immunotherapy is a rapidly evolving field that offers a novel paradigm for cancer treatment: therapies focus on enhancing the immune system's innate and adaptive anti-tumor response. Early immunotherapeutics have achieved impressive clinical outcomes and monoclonal antibodies are now integral to therapeutic strategies in a variety of cancers. However, only recently have antibodies targeting innate immune cells entered clinical development. Innate immune effector cells play important roles in generating and maintaining antitumor immunity. Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) are important innate immune mechanisms for tumor eradication. These cytolytic processes are initiated by the detection of a tumor-targeting antibody and can be augmented by activating co-stimulatory pathways or blocking inhibitory signals on innate immune cells. The combination of FDA-approved monoclonal antibodies with innate effector-targeting antibodies has demonstrated potent preclinical therapeutic synergy and early-phase combinatorial clinical trials are ongoing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Clinical Experience With Radiation Therapy in the Management of Neurofibromatosis-Associated Central Nervous System Tumors

    International Nuclear Information System (INIS)

    Wentworth, Stacy; Pinn, Melva; Bourland, J. Daniel; Guzman, Allan F. de; Ekstrand, Kenneth; Ellis, Thomas L.; Glazier, Steven S.; McMullen, Kevin P.; Munley, Michael; Stieber, Volker W.; Tatter, Stephen B.; Shaw, Edward G.

    2009-01-01

    Purpose: Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. Methods and Materials: Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. Results: Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. Conclusions: RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors

  12. Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy.

    Science.gov (United States)

    McWilliams, Geoffrey D; SantaCruz, Karen; Hart, Blaine; Clericuzio, Carol

    2016-01-01

    Noonan syndrome (NS) is an autosomal dominant developmental disorder caused by mutations in the RAS-MAPK signaling pathway that is well known for its relationship with oncogenesis. An 8.1-fold increased risk of cancer in Noonan syndrome has been reported, including childhood leukemia and solid tumors. The same study found a patient with a dysembryoplastic neuroepithelial tumor (DNET) and suggested that DNET tumors are associated with NS. Herein we report an 8-year-old boy with genetically confirmed NS and a DNET. Literature review identified eight other reports, supporting the association between NS and DNETs. The review also ascertained 13 non-DNET brain tumors in individuals with NS, bringing to 22 the total number of NS patients with brain tumors. Tumor growth while receiving growth hormone (GH) occurred in our patient and one other patient. It is unknown whether the development or progression of tumors is augmented by GH therapy, however there is concern based on epidemiological, animal and in vitro studies. This issue was addressed in a 2015 Pediatric Endocrine Society report noting there is not enough data available to assess the safety of GH therapy in children with neoplasia-predisposition syndromes. The authors recommend that GH use in children with such disorders, including NS, be undertaken with appropriate surveillance for malignancies. Our case report and literature review underscore the association of NS with CNS tumors, particularly DNET, and call attention to the recommendation that clinicians treating NS patients with GH do so with awareness of the possibility of increased neoplasia risk. © 2015 Wiley Periodicals, Inc.

  13. Morphological changes in skin tumors caused by pulsed laser irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Moskalik, K G; Lipova, V A; Neyshtadt, E L

    1979-01-01

    Morphological changes induced by treating melanomas, basaloma and flatcell skin cancers with a pulsed neodymium laser at 1060 nm, pulse length 1 msec and energy 250 to 500 J/cm/sup 2/, were studied using impressions and scrapings from the affected area. Nuclear pyknosis, nuclear and cellular elongation, vacuolization, frequent complete loss of cytoplasm, particulaly in the zone of direct irradiation, and loss of cellular structure were seen. These dystrophic changes increased with closeness to the zone of direct irradiation, culminating in necrosis. Formed and decomposed blood elements and melanin accumulated in the intracellular spaces, due to disruption of capillaries and small arteries and veins. Fewer and more aggregated melanoblasts were found after melanoma irradiation. Nuclear chromatin fusion, cytoplasmic changes and altered cell shape were observed. Basaloma cells were clustered and elongated after irradiation, with many fibrous structures and loss of cellular elements. Cytoplasmic vacuolization and lysis, bare nuclei, karyolysis, karyorrhexis and karyopyknosis were seen in corneous flat-cell cancer. In the few cases in which malignant cells were found under the scab from the first treatment the procedure was repeated. The morphological changes induced by pulsed laser irradiation are very similar to electrocoagulation necrosis, but are more localized. The ability of low and middle energy lasers to induce thrombosis and coagulation in vascular walls reduced the probability of hematogenic tumor cell dissemination. Cytological examination is highly effective in determining the degree of radical skin cancer healing due to laser treatment. 12 references, 2 figures.

  14. Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment.

    Science.gov (United States)

    Ito, Koichi; Stannard, Kimberley; Gabutero, Elwyn; Clark, Amanda M; Neo, Shi-Yong; Onturk, Selda; Blanchard, Helen; Ralph, Stephen J

    2012-12-01

    The microenvironment of a tumor is a highly complex milieu, primarily characterized by immunosuppression, abnormal angiogenesis, and hypoxic regions. These features promote tumor progression and metastasis, resulting in poor prognosis and greater resistance to existing cancer therapies. Galectin-1 is a β-galactoside binding protein that is abundantly secreted by almost all types of malignant tumor cells. The expression of galectin-1 is regulated by hypoxia-inducible factor-1 (HIF-1) and it plays vital pro-tumorigenic roles within the tumor microenvironment. In particular, galectin-1 suppresses T cell-mediated cytotoxic immune responses and promotes tumor angiogenesis. However, since galectin-1 displays many different activities by binding to a number of diverse N- or O-glycan modified target proteins, it has been difficult to fully understand how galectin-1 supports tumor growth and metastasis. This review explores the importance of galectin-1 and glycan expression patterns in the tumor microenvironment and the potential effects of inhibiting galectin-1 as a therapeutic target for cancer treatment.

  15. Basic study for development of new tumor specific agents for neutron capture therapy

    International Nuclear Information System (INIS)

    Matsumura, Akira; Nakagawa, Kunio; Yoshii, Yoshihiko; Nose, Tadao

    1994-01-01

    New tissue specific agents for neutron capture therapy was studied. Monoclonal labeled gadolinium-DTPA (Gd-MoAb) and porphyrin (ATN-10)-Gd-DTPA (Gd-ATN10) were studied as possible agents by using 9-L experimental brain tumor model. The tissue concentration were analyzed with magnetic resonance imaging (MRI) and inductively coupled plasma (ICP) analyzer. Gd-MoAb showed persistent retention in the tumor on MRI, but tissue gadolinium concentration was not detectable in the tumor by ICP analyzer, while there was high accumulation of Gd-MoAb in the liver. Gd-ATN10 showed prolonged and high accumulation in the tumor up to 48 hours on MRI. Gadolinium concentration reached up to 9 ppm in the tumor by 0.02 mmol/kg administration, but it disappeared within 6 hours after administration. This dissociation between MRI and ICP analysis was due to separation of ATN-10 and Gd-DTPA. As conclusions, the porphyrin compounds are potential agents for delivering gadolinium or boron specific to the tumor tissue, thus further improvement such as more stable conjugation between porphyrinfic to the tumor tissue, thus further improvement such as more stable conjugation between porphyrin and Gd-DTPA is needed. (author)

  16. Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

    2016-06-01

    The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Radiation treatment causes macrophages

  17. Brain tumors and synchrotron radiation: Methodological developments in quantitative brain perfusion imaging and radiation therapy

    International Nuclear Information System (INIS)

    Adam, Jean-Francois

    2005-01-01

    High-grade gliomas are the most frequent type of primary brain tumors in adults. Unfortunately, the management of glioblastomas is still mainly palliative and remains a difficult challenge, despite advances in brain tumor molecular biology and in some emerging therapies. Synchrotron radiation opens fields for medical imaging and radiation therapy by using monochromatic intense x-ray beams. It is now well known that angiogenesis plays a critical role in the tumor growth process and that brain perfusion is representative of the tumor mitotic activity. Synchrotron radiation quantitative computed tomography (SRCT) is one of the most accurate techniques for measuring in vivo contrast agent concentration and thus computing precise and accurate absolute values of the brain perfusion key parameters. The methodological developments of SRCT absolute brain perfusion measurements as well as their preclinical validation are detailed in this thesis. In particular, absolute cerebral volume and blood brain barrier permeability high-resolution (pixel size 2 ) parametric maps were reported. In conventional radiotherapy, the treatment of these tumors remains a delicate challenge, because the damages to the surrounding normal brain tissue limit the amount of radiation that can be delivered. One strategy to overcome this limitation is to infuse an iodinated contrast agent to the patient during the irradiation. The contrast agent accumulates in the tumor, through the broken blood brain barrier, and the irradiation is performed with kilovoltage x rays, in tomography mode, the tumor being located at the center of rotation and the beam size adjusted to the tumor dimensions. The dose enhancement results from the photoelectric effect on the heavy element and from the irradiation geometry. Synchrotron beams, providing high intensity, tunable monochromatic x rays, are ideal for this treatment. The beam properties allow the selection of monochromatic irradiation, at the optimal energy, for a

  18. Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy.

    Science.gov (United States)

    Jin, Rong; Guo, Xuelian; Dong, Lingli; Xie, Enyuan; Cao, Aoneng

    2017-10-01

    A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH 2 ) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH 2 . These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Neuroplastic Response After Radiation Therapy for Pediatric Brain Tumors: A Pilot Study

    International Nuclear Information System (INIS)

    Armstrong, Carol L.; Fisher, Michael J.; Li, Yimei; Lustig, Robert A.; Belasco, Jean B.; Minturn, Jane E.; Hill-Kayser, Christine E.; Batra, Sonny; Phillips, Peter C.

    2016-01-01

    Purpose: Clinically effective measurement of cognitive toxicity from photon radiation therapy (XRT) should be accurate, sensitive, and specific. This pilot study tested translational findings on phasic changes in children's memory systems that are sensitive and insensitive to toxic XRT effects to identify a possible neuroplastic effect. Methods and Materials: Memory processes were prospectively tested before XRT and at 3 later time points up to 2 years in 35 children with mixed primary brain tumors who had not experienced recurrence. Memory processes were verbal-semantic, visual-semantic, and visual-perceptual, including accuracy, speed to recall, encoding, retrieval, and recognition. The mixed-effects model included time (to estimate slope), covariates (age, tumor locus, XRT field, and medications) as fixed effects, and individual random intercepts. A sensitivity analysis examined the influence of XRT dose to the hippocampi on memory. Results: Retrieval from long-term verbal-semantic memory declined 2 months after completing XRT, as seen in adults, and was lowest at 1 year, which was delayed in comparison with adults. Double dissociation from visual-perceptual memory at baseline and 2 months was found, consistent with adults. Recovery was demonstrated 2 years after XRT. Patterns were unchanged when dose to hippocampus was included in the model. Conclusions: Verbal and semantic long-term retrieval is specifically sensitive to XRT-related cognitive dysfunction, without effect on visual-perceptual memory. Children reached nadir in XRT-sensitive memory 1 year after XRT and recovered by 2 years, which is later than that observed in adults. The protracted period of post-XRT injury may represent the maturation of the human hippocampus and white matter into late adolescence.

  20. Neuroplastic Response After Radiation Therapy for Pediatric Brain Tumors: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Carol L., E-mail: armstrongc@email.chop.edu [Neuro-Oncology Section, Children' s Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Fisher, Michael J. [Neuro-Oncology Section, Children' s Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Li, Yimei [Oncology Division, Children' s Hospital of Philadelphia, and Department of Biostatistics and Epidemiology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Lustig, Robert A. [Department of Radiation Oncology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Belasco, Jean B.; Minturn, Jane E. [Neuro-Oncology Section, Children' s Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hill-Kayser, Christine E.; Batra, Sonny [Department of Radiation Oncology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Phillips, Peter C. [Neuro-Oncology Section, Children' s Hospital of Philadelphia, and Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2016-07-01

    Purpose: Clinically effective measurement of cognitive toxicity from photon radiation therapy (XRT) should be accurate, sensitive, and specific. This pilot study tested translational findings on phasic changes in children's memory systems that are sensitive and insensitive to toxic XRT effects to identify a possible neuroplastic effect. Methods and Materials: Memory processes were prospectively tested before XRT and at 3 later time points up to 2 years in 35 children with mixed primary brain tumors who had not experienced recurrence. Memory processes were verbal-semantic, visual-semantic, and visual-perceptual, including accuracy, speed to recall, encoding, retrieval, and recognition. The mixed-effects model included time (to estimate slope), covariates (age, tumor locus, XRT field, and medications) as fixed effects, and individual random intercepts. A sensitivity analysis examined the influence of XRT dose to the hippocampi on memory. Results: Retrieval from long-term verbal-semantic memory declined 2 months after completing XRT, as seen in adults, and was lowest at 1 year, which was delayed in comparison with adults. Double dissociation from visual-perceptual memory at baseline and 2 months was found, consistent with adults. Recovery was demonstrated 2 years after XRT. Patterns were unchanged when dose to hippocampus was included in the model. Conclusions: Verbal and semantic long-term retrieval is specifically sensitive to XRT-related cognitive dysfunction, without effect on visual-perceptual memory. Children reached nadir in XRT-sensitive memory 1 year after XRT and recovered by 2 years, which is later than that observed in adults. The protracted period of post-XRT injury may represent the maturation of the human hippocampus and white matter into late adolescence.

  1. Long-term follow-up results of combination therapy of surgery and gamma knife on pituitary tumor

    International Nuclear Information System (INIS)

    Ikeda, Hidetoshi; Yoshimoto, Takashi; Shirokura, Hideshi

    1997-01-01

    Usefulness of the combination therapy for invasive pituitary tumor with surgery and gamma knife (GK) was evaluated on 17 cases followed for >2 years. Tumors involved ACTH cell adenoma, GH cell adenoma, mixed GH and PRL, purihormonal adenoma, gonadotrophic cell adenoma, GH cell adenoma and null cell adenoma, which were divided into I and II group since adverse effects by GK on the normal pituitary tissues could be evaluated according to tumor growth and abnormal hormone secretion. Irradiation was carried out to make the marginal dose of around 30 (15-35) Gy and center dose of 25-70 Gy on the gland, and marginal dose of <10 Gy on optic nerve. After GK, follow-up was done by pituitary hormone values, tests for sight and visual field and MRI examination. Hypopituitarism was seen in 67% with 100% remission of Cushing's disease. MRI revealed that the adenoma changed to fibrosis (type 1) with increasing Gd-enhancement or to cystic necrosis (type 2) without Gd-enhancement. Values for GH, cortisol and ACTH turned to normal ones. Thus the combination therapy was found useful. (K.H.)

  2. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

    2015-10-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.

  3. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    International Nuclear Information System (INIS)

    Koritzinsky, Marianne

    2015-01-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers

  4. Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

    Science.gov (United States)

    Qiana, Xian-Ling; Li, Jun; Wei, Ran; Lin, Hui; Xiong, Li-Xia

    2018-05-09

    Anticancer chemotherapeutics have a lot of problems via conventional drug delivery systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

    Science.gov (United States)

    Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

    2015-07-01

    The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  6. Dosimetric comparison of intensity modulated radiation, Proton beam therapy and proton arc therapy for para-aortic lymph node tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hoon [Dept. of Radiation Oncology, Konyang University Hospital. Daejeon (Korea, Republic of)

    2014-12-15

    To test feasibility of proton arc therapy (PAT) in the treatment of para-aortic lymph node tumor and compare its dosimetric properties with advanced radiotherapy techniques such as intensity modulated radiation therapy (IMRT) and conventional 3D conformal proton beam therapy (PBT). The treatment plans for para-aortic lymph node tumor were planned for 9 patients treated at our institution using IMRT, PBT, and PAT. Feasibility test and dosimetric evaluation were based on comparisons of dose volume histograms (DVHs) which reveal mean dose, D{sub 30%}, D{sub 60%}, D{sub 90%}, V{sub 30%}, V{sub 60%}, V{sub 90}%, organ equivalent doses (OEDs), normal tissue complication probability (NTCP), homogeneity index (HI) and conformity index (CI). The average doses delivered by PAT to the liver, kidney, small bowel, duodenum, stomach were 7.6%, 3%, 17.3%, 26.7%, and 14.4%, of the prescription dose (PD), respectively, which is higher than the doses delivered by IMRT (0.4%, 7.2%, 14.2%, 15.9%, and 12.8%, respectively) and PBT (4.9%, 0.5%, 14.12%, 16.1% 9.9%, respectively). The average homogeneity index and conformity index of tumor using PAT were 12.1 and 1.21, respectively which were much better than IMRT (21.5 and 1.47, respectively) and comparable to PBT (13.1 and 1.23, respectively). The result shows that both NTCP and OED of PAT are generally lower than IMRT and PBT. This study demonstrates that PAT is better in target conformity and homogeneity than IMRT and PBT but worse than IMRT and PBT for most of dosimetric factor which indicate that PAT is not recommended for the treatment of para-aortic lymph node tumor.

  7. [Synergistic effect of cell kinetics-directed chemo-endocrine therapy on experimental mammary tumors].

    Science.gov (United States)

    Ueki, H

    1987-11-01

    We tried to demonstrate that the cell kinetics-directed chemoendocrine therapy is more effective on hormone dependent breast cancer than empirical combination of the endocrine therapy and chemotherapy. Cell kinetics of each tumor was measured by flow cytometric analysis. Estrogen dependent human breast cancer cell line MCF-7 was used in vitro. In vivo, androgen dependent SC-115 carcinoma was transplanted to DDS mice. In vitro, tamoxifen was administered as the endocrine therapy. In vivo, we carried out testectomy on DDS mice. Effect of the endocrine therapy on the cell kinetics of the tumor was thought to be G1-S depression. High density 5FU was administered as the chemotherapeutic agents, whose content was 1 microgram/ml in vitro and 40 mg/kg in vivo. 5FU brought temporary decrease of cells in S phase. Only anteceding 5FU administration had synergistic effect in combination of 5FU and the endocrine therapy. 5FU was convinced to act more effectively on cells in S phase, so it was shown that cell kinetics-directed schedule was superior to the empirical treatment schedule in chemoendocrine therapy.

  8. Anti-tumor effects of Egr-IFN gamma gene therapy combined with {sup 125}I-UdR radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jingguo, Zhao [No.403 Hospital of PLA, Dalian (China); Yanjun, Ni; Xiangfu, Song; Yanyi, Li; Wei, Yang; Ting, Sun; Qingjie, Ma; Fengtong, Gao

    2008-12-15

    Objective: To explore the anti-tumor effects of Egr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy in mice bearing H22 hepatocarcinoma and its mechanism. Methods: The recombinant plasmid pcDNAEgr-IFNgamma mixed with liposome was injected into tumor. 48 h later, 370 kBq {sup 125}I-UdR was injected into tumor. The tumor growth rates at different times were observed. After 3 d gene-radionuclide therapy, the concentration of IFNgamma in cytoplasm of H22 cells and cytotoxic activities of splenic CTL of the mice in different groups were examined. Results: The tumor growth rates of pcDNAEgr-IFNgamma + {sup 125}I-UdR group were obviously lower than those of control group, {sup 125}I-UdR group and pcDNAEgr-1 + {sup 125}I-UdR group 6-15 d after gene-radionuclide therapy. IFNgamma protein was found in cytoplasm of H22 cells in pcDNAEgr-IFNgamma + {sup 125}I-UdR group after 3 d gene-radionuclide therapy. Cytotoxic activity of splenic CTL in pcDNAEgr-IFNgamma + {sup 125}I-UdR group was significantly higher than that in the other groups (P<0.01). Conclusions: The anti-tumor effects in vivo of pcDNAEgr-IFNgamma gene therapy combined with {sup 125}I-UdR radionuclide therapy are better than those of {sup 125}I-UdR therapy. (authors)

  9. Hypoxia targeting therapy with prodrug specifically stabilized and activated in hypoxic tumor cells

    International Nuclear Information System (INIS)

    Kondoh, S.K.; Ueda, T.; Harada, H.; Hiraoka, M.; Akagi, K.

    2003-01-01

    Hypoxia fraction in tumors is associated with increased metastasis and poor survival in patients suffering from malignant tumors such as the head and neck, cervical or breast cancers. Hypoxia can be a direct cause of therapeutic resistance because some drugs and radiation require oxygen to be maximally cytotoxic. Recently we have reported a novel hypoxia targeting prodrug, TOP3, which is a fusion protein, composed of HIV TAT protein transduction domain, a part of HIF1 α ODD domain, and Procaspase-3. TOP3 can be transferred into every cell both in vitro and in vivo but becomes stable only in hypoxic cells, in which TOP3 is activated and induces apoptosis. The application of this fusion protein to a tumor-bearing mouse resulted in significant suppression of the tumor growth and even in reduction of the tumor mass without any obvious side effects. The administrations of TOP3 in combination with a low dose of X-ray showed an additive antitumor effect on pancreatic tumor cells. Furthermore, we show that the rodent model of ascites generated by malignant cells provides an excellent platform of testing hypoxia targeting drugs, since it comprises homogeneous fluid with tumor cells surviving and proliferating under hypoxic condition. TOP3 induced apoptosis of AH130, rat ascites hepatoma cells, in vitro only under hypoxic but not normoxic condition. Intraperitoneal administration of TOP3 prolonged life span of the rats with AH130 derived malignant ascites. Sixty percent of the treated rats were cured of ascites without recurrence for more than six months, in contrast all untreated rats died within 20 days after tumor cell inoculation. These results strongly suggest that TOP3 would provide a new strategy for hypoxia targeting therapy and that the combination of TOP3 with radiotherapy or chemotherapy may provide a new strategy for annihilating malignant tumors

  10. Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

    Science.gov (United States)

    MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

    2014-01-01

    The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

  11. Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy

    International Nuclear Information System (INIS)

    Goodman, J.H.; McGregor, J.M.; Clendenon, N.R.; Gahbauer, R.A.; Barth, R.F.; Soloway, A.H.; Fairchild, R.G.

    1990-01-01

    This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity

  12. Lacunar infarction in brain tumor patients. Chronic stage complication after radiation therapy

    International Nuclear Information System (INIS)

    Nakazaki, Kiyoshi; Titoku, Shirou; Ota, Shinzou; Sato, Mitiyoshi; Kobanawa, Satoshi; Tutida, Kazuyuki; Tanaka, Yasue; Goto, Katsuya; Ota, Taisei

    2007-01-01

    The authors reported two relatively young adults with lacunar infarction that took place many years after radiation therapy. The first case was that of a 41-year-old male presenting with a slight decrease in consciousness and right hemiparesis of sudden occurrence. MRI revealed a lacunar infarction in the left internal capsule. This patient had received radiation therapy and chemotherapy for a right basal ganglia germinoma when he was 24 years old. The tumor completely disappeared and he was able to return to work. The second case was a 24-year-old female presenting with dysesthesia in the right upper extremity and nausea of sudden occurrence. MRI disclosed a lacunar infarct in the right corona radiata. The patient had received radiation therapy for a suprasellar tumor when she was 11 years old. The tumor considerably decreased in size and the patient conducted normal social life thereafter. MRI showed a lacunar infarction in the right corona radiata. Review of the literature was made and the possibility of radiation therapy as a causative factor of the lacunar infarction in relatively young adults was discussed. (author)

  13. Improvement of Antitumor Therapies Based on Vaccines and Immune-Checkpoint Inhibitors by Counteracting Tumor-Immunostimulation

    Directory of Open Access Journals (Sweden)

    Paula Chiarella

    2018-01-01

    Full Text Available Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors, counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth.

  14. Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

    International Nuclear Information System (INIS)

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

    2008-01-01

    Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer

  15. Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Brian C. Wilson

    2015-01-01

    Full Text Available Excited-state singlet oxygen (1O2, generated during photodynamic therapy (PDT, is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers. Its relative concentration in cells or tissues can be measured directly through its near-infrared (NIR luminescence emission, which has correlated well with in vitro cell and in vivo normal skin treatment responses. Here, its correlation with the response of tumor tissue in vivo is examined, using the photosensitizer meso-tetrahydroxyphenylchlorin (mTHPC in an animal model comprising luciferase- and green fluorescent protein (GFP-transduced gliosarcoma grown in a dorsal window chamber. The change in the bioluminescence signal, imaged pretreatment and at 2, 5 and 9 d post treatment, was used as a quantitative measure of the tumor response, which was classified in individual tumors as "non", "moderate" and "strong" in order to reduce the variance in the data. Plotting the bioluminescence-based response vs the 1O2 counts demonstrated clear correlation, indicating that 1O2 luminescence provides a valid dosimetric technique for PDT in tumor tissue.

  16. Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema

    Energy Technology Data Exchange (ETDEWEB)

    Binkley, Michael S. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Shrager, Joseph B. [Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Leung, Ann N. [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Popat, Rita [Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California (United States); Trakul, Nicholas [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California (United States); Atwood, Todd F.; Chaudhuri, Aadel [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Maxim, Peter G. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian, E-mail: Diehn@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W., E-mail: BWLoo@Stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

    2014-09-01

    Purpose: Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema. Methods and Materials: We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3). Results: 27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, −0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, −3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r{sup 2}=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r{sup 2}=0.47, P<.0001). Conclusions: We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across

  17. Basic study of gadolinium neutron capture therapy for malignant brain tumors

    International Nuclear Information System (INIS)

    Oda, Yoshifumi; Takagaki, Masao; Miyatake, Shin-ichi; Kikuchi, Haruhiko

    1994-01-01

    We measured the time-course of gadolinium take up in 91 brain tumor tissues obtained during surgical operations, and compared those results against measurements of gadolinium concentration changes in serum in 31 cases of both malignant and benign brain tumors. The contents of gadolinium in tissues were measured using the ICP spectroscopic method. The results shown wide variations in each class. In malignant gliomas, the maximum Tumor/Blood (T/B) ratio is around 10-30%, reached in 30-40 minutes after i.v. injection of Gd-DTPA, but it is rapidly excreted from the tissue and decreased to lower than 10% at 60 minutes after the injection. There is no measurable correlation between the tissue concentration of gadolinium and the histological grading of astrocytomas. In the case of meningiomas, T/B ratio is 20-30%, and has a tendency to increase gradually even 60 minutes after administration. In one case of rapid recurrent meningioma, the T/B ratio beyond 100% and became 640% at 85 minutes after the injection. In this case, Gd-NC therapy will promise the best result. The main clinical effect of Gd-NCT is due to the 6.30MeV γ-rays, which have a long pathway, and 1.53MeV high-RBE Auger electron. Intraparenchynal capillaries in the brain usually have a thickness of 3.5μm of endothelial cells. The capillaries occupate about 4% of the area of any cross-sectional plane of the brain. Under these conditions, Gd has full therapeutic effect without damaging either normal brain tissues or vascular components, provided the T/B ratio is kept higher than 10%. The further problem of the Gd-NCT is that (1) Gd is situated exclusively in the extracellular spaces as opposed to intracellular-or intranuclearspaces. The development of Gd compounds which will be incorporated into the nucleus is required. (2) It is necessary to keep a high gadolinium T/B ratio during the whole irradiation period, which is 1-2 hours in a 5MW reactor such as the one being used at Kyoto University. (J.P.N.)

  18. Efficacy of percutaneous microwave coagulation therapy for nodular hepatic tumor : a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seon Hee; Bang, Sun Woo; Baek, Seung Il; Kim, Ho Kyun [Inje Univ. College of Medicine, Seoul (Korea, Republic of); Kim, Jeong Seok [Dongguk Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-04-01

    Percutaneous microwave coagulation therapy (PMCT) uses a new energy source, microwave, in the treatment of solid neoplasms. We evaluated the efficacy of PMCT for nodular hepatic tumors in nine patients. Between December 1998 and June 1999, we performed PMCT in six patients with hepatocelluar carcinoma (HCC), two with one and three metastatic nodules each from colon cancer, and one with adenomatous hyperplasia. Four patients were female and five were male, and their age ranged between 44 and 71 (mean, 58.8) years. Under sonographic guidance a 14-gauge guiding needle was inserted percutaneously toward the lesion, and within it a needle electrode was precisely positioned. Microwave 2450MHz in frequency and with 60 or 80-watt emission was generated for 80{approx}90 seconds. We evaluated the ultrasound findings obtained during the procedure, pre-PMCT and follow-up CT images, changes in tumor marker(AFP or CA19-9) levels and the results of liver function tests, and complications arising during the six-month period following PMCT. Immediately after microwave emission, characteristic hyperechogenicity appeared on the real-time sonogram. Two patients with HCC underwent CT before PMCT, and typical enhancement during the arterial phase and washout during the portovenous phase was observed. In one patient, two metastatic lesions from colon cancer showed delayed enhancement on pre-PMCT CT. Initial follow-up CT, performed between I and 4 weeks after the PMCT procedure, showed that eight lesions-including two HCCs which were highly enhanced on CT before PMCT-showed no contrast enhancement, and three others showed delayed enhancement. Two of the eight lesions which showed no contrast enhancement at initial follow-up CT were markedly decreased in size (from 2.9 and 4.0 cm to 1.0 and 2.0 cm, respectively) at subsequent follow-up 3 months and 6 months later, respectively. One of the three lesions showing delayed enhancement had increased in size from 4.1 to 5.5 cm at subsequent

  19. Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

    2016-01-01

    Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

  20. Biomedical Application of Electroporation: Electrochemotherapy and Electrogene Therapy in Treatment of Cutaneous and Deep Seated Tumors

    International Nuclear Information System (INIS)

    Sersa, G.; Cemazar, M.; Gadzijev, E.; Edhemovic, I.; Brecelj, E.; Snoj, M.

    2011-01-01

    Several novel tumor-targeting and drug delivery approaches in cancer treatment are currently undergoing intensive investigation in order to increase the therapeutic index - among them physical approaches such as tissue electroporation. Electroporation of tissue increases the membrane permeability of cells, specifically in the area that is exposed to the applied electric pulses. Electroporation-based cancer treatment approaches are currently undergoing intensive investigation in the field of drug (electrochemo-therapy) and gene (electrogene therapy) delivery. Electrochemotherapy, since its beginnings in the late 1980s, has evolved into a clinically verified treatment approach for cutaneous and subcutaneous tumor nodules. It is defined as a local treatment which, via cell membrane permeabilising electric pulses, potentiates the cytotoxicity of non-permeant or poorly permeant anticancer drugs with high intrinsic cytotoxicity at the site of electric pulse application. Suitable candidates for electrochemotherapy are limited to those drugs that are hydrophilic and lack transport system in the membrane. Up to date two drugs have been identified as potential candidates for electrochemotherapy: bleomycin, which cytotoxicity in vitro can be potentiated up to several-1000-fold by electroporation of cells, and cisplatin whose cytotoxicity increased by up to 80-fold due to electroporation. High antitumor effectiveness of electrochemotherapy was demonstrated on fibrosarcomas, melanoma, and carcinomas in mice, rats and rabbits; good clinical results were also obtained in veterinary medicine on cats, dogs and horses. In these studies it was demonstrated that with drug doses that have minimal or no antitumor effectiveness, high (up to 75 %) complete responses of the electrochemotherapy-treated tumors were obtained. The drug doses used were so low that they had no systemic toxicity. Also the application of electric pulses to the tumors had no antitumor effectiveness and no systemic

  1. 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.

  2. An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

    Science.gov (United States)

    Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

    2015-09-21

    A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.

  3. Towards an integrative computational model for simulating tumor growth and response to radiation therapy

    Science.gov (United States)

    Marrero, Carlos Sosa; Aubert, Vivien; Ciferri, Nicolas; Hernández, Alfredo; de Crevoisier, Renaud; Acosta, Oscar

    2017-11-01

    Understanding the response to irradiation in cancer radiotherapy (RT) may help devising new strategies with improved tumor local control. Computational models may allow to unravel the underlying radiosensitive mechanisms intervening in the dose-response relationship. By using extensive simulations a wide range of parameters may be evaluated providing insights on tumor response thus generating useful data to plan modified treatments. We propose in this paper a computational model of tumor growth and radiation response which allows to simulate a whole RT protocol. Proliferation of tumor cells, cell life-cycle, oxygen diffusion, radiosensitivity, RT response and resorption of killed cells were implemented in a multiscale framework. The model was developed in C++, using the Multi-formalism Modeling and Simulation Library (M2SL). Radiosensitivity parameters extracted from literature enabled us to simulate in a regular grid (voxel-wise) a prostate cell tissue. Histopathological specimens with different aggressiveness levels extracted from patients after prostatectomy were used to initialize in silico simulations. Results on tumor growth exhibit a good agreement with data from in vitro studies. Moreover, standard fractionation of 2 Gy/fraction, with a total dose of 80 Gy as a real RT treatment was applied with varying radiosensitivity and oxygen diffusion parameters. As expected, the high influence of these parameters was observed by measuring the percentage of survival tumor cell after RT. This work paves the way to further models allowing to simulate increased doses in modified hypofractionated schemes and to develop new patient-specific combined therapies.

  4. HUMAN NK CELLS: FROM SURFACE RECEPTORS TO THE THERAPY OF LEUKEMIAS AND SOLID TUMORS

    Directory of Open Access Journals (Sweden)

    LORENZO eMORETTA

    2014-03-01

    Full Text Available Natural Killer (NK cells are major effector cells of the innate immunity. The discovery, over two decades ago, of MHC-class I specific NK receptors and subsequently of activating receptors, recognizing ligands expressed by tumor or virus-infected cells, paved the way to our understanding of the mechanisms of selective recognition and killing of tumor cells. Although NK cells can efficiently kill tumor cells of different histotypes in vitro, their activity may be limited in vivo by their inefficient trafficking to tumor lesions and by the inhibition of their function induced by tumor cells themselves and by the tumor microenvironment. On the other hand, the important role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic cell (HSC transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvHD and graft rejection.

  5. Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors

    International Nuclear Information System (INIS)

    Welzel, Grit; Mai, Sabine K.; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Wenz, Frederik; Fleckenstein, Katharina; Duke University Medical Center Durham, NC

    2008-01-01

    The objective of the current study was to evaluate the acute effects of cranial radiation therapy (CNS-RT) using different radiation doses (0, 1.8, 2, 3, ≤ 20 Gy) on cognitive function with special emphasis on memory. We assessed patients with and without intracranial tumors to distinguish between direct and indirect radiation effects on brain tissue. Eighty-two patients were evaluated with neuropsychological testing before and acutely after radiotherapy (RT). Sixty-four patients received RT to the brain (55 with, 9 without intracranial tumor). Eighteen patients treated with RT to the breast served as controls. Patients with intracranial tumor demonstrated attention (19-38th percentile) and verbal memory scores (34-46th percentile) below the population average at baseline. The average Verbal Memory score was significantly different between patients with intracranial tumor and controls both at baseline (38th vs. 58th percentile) and after irradiation (27th vs. 52th percentile). Patients with preexisting peritumoral edema performed worse than patients without edema and controls. Radiation dose-related deficits were seen for working memory performance in patients with intracranial tumor. Our data indicate no measurable impairment of cognitive functioning acutely after prophylactic cranial irradiation. Patients with intracranial tumor show a deterioration of almost all memory functions with a dose-dependent impairment in working memory. Patients with preexisting peritumoral brain edema show the strongest deterioration. (orig.)

  6. Expanding roles for CD4 T cells and their subpopulations in tumor immunity and therapy

    Directory of Open Access Journals (Sweden)

    Mark J Dobrzanski

    2013-03-01

    Full Text Available The importance of CD4 T cells in orchestrating the immune system and their role in inducing effective T cell-mediated therapies for the treatment of patients with select established malignancies are undisputable. Through a complex and balanced array of direct and indirect mechanisms of cellular activation and regulation, this functionally diverse family of lymphocytes can potentially promote tumor eradication, long-term tumor immunity and aid in establishing and/or rebalancing immune cell homeostasis through interaction with other immune cell populations within the highly dynamic tumor environment. However, recent studies have uncovered additional functions and roles for CD4 T cells, some of which are independent of other lymphocytes, that can not only influence and contribute to tumor immunity but paradoxically promote tumor growth and progression. Here, we review the recent advances in our understanding of the various CD4 T cell lineages and their signature cytokines in disease progression and/or regression. We discuss their direct and indirect mechanistic interplay among themselves and with other responding cells of the antitumor response, their potential roles and abilities for "plasticity" and memory cell generation within the hostile tumor environment and their potentials in cancer treatment and adoptive immunotherapies.

  7. Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Welzel, Grit; Mai, Sabine K.; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Wenz, Frederik [University Medical Center Mannheim, Heidelberg Univ. (Germany). Dept. of Radiation Oncology; Fleckenstein, Katharina [University Medical Center Mannheim, Heidelberg Univ. (Germany). Dept. of Radiation Oncology]|[Duke University Medical Center Durham, NC (United States). Dept. of Radiation Oncology

    2008-12-15

    The objective of the current study was to evaluate the acute effects of cranial radiation therapy (CNS-RT) using different radiation doses (0, 1.8, 2, 3, {<=} 20 Gy) on cognitive function with special emphasis on memory. We assessed patients with and without intracranial tumors to distinguish between direct and indirect radiation effects on brain tissue. Eighty-two patients were evaluated with neuropsychological testing before and acutely after radiotherapy (RT). Sixty-four patients received RT to the brain (55 with, 9 without intracranial tumor). Eighteen patients treated with RT to the breast served as controls. Patients with intracranial tumor demonstrated attention (19-38th percentile) and verbal memory scores (34-46th percentile) below the population average at baseline. The average Verbal Memory score was significantly different between patients with intracranial tumor and controls both at baseline (38th vs. 58th percentile) and after irradiation (27th vs. 52th percentile). Patients with preexisting peritumoral edema performed worse than patients without edema and controls. Radiation dose-related deficits were seen for working memory performance in patients with intracranial tumor. Our data indicate no measurable impairment of cognitive functioning acutely after prophylactic cranial irradiation. Patients with intracranial tumor show a deterioration of almost all memory functions with a dose-dependent impairment in working memory. Patients with preexisting peritumoral brain edema show the strongest deterioration. (orig.)

  8. Gene therapy for patients with advanced solid tumors

    DEFF Research Database (Denmark)

    Spanggaard, Iben; Dahlstroem, Karin; Laessoee, Line

    2017-01-01

    -computed tomography (PET-CT) scans. RESULTS: Seven patients were enrolled and treated at dose levels from 50 to 250 μg of plasmid AMEP, the study was terminated early due to cessation of plasmid production. Minimal systemic toxicity was observed and only transient mild pain was associated with the delivery......BACKGROUND: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide...... of the electric pulses. MRI of the treated muscles revealed discrete intramuscular edema 24 h after treatment. The changes in the muscle tissue resolved within 2 weeks after treatment. Peak concentrations of plasmid AMEP was detected only in plasma within the first 24 hours after injection. Protein AMEP could...

  9. A partial differential equation model and its reduction to an ordinary differential equation model for prostate tumor growth under intermittent hormone therapy.

    Science.gov (United States)

    Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

    2014-10-01

    Hormonal therapy with androgen suppression is a common treatment for advanced prostate tumors. The emergence of androgen-independent cells, however, leads to a tumor relapse under a condition of long-term androgen deprivation. Clinical trials suggest that intermittent androgen suppression (IAS) with alternating on- and off-treatment periods can delay the relapse when compared with continuous androgen suppression (CAS). In this paper, we propose a mathematical model for prostate tumor growth under IAS therapy. The model elucidates initial hormone sensitivity, an eventual relapse of a tumor under CAS therapy, and a delay of a relapse under IAS therapy, which are due to the coexistence of androgen-dependent cells, androgen-independent cells resulting from reversible changes by adaptation, and androgen-independent cells resulting from irreversible changes by genetic mutations. The model is formulated as a free boundary problem of partial differential equations that describe the evolution of populations of the abovementioned three types of cells during on-treatment periods and off-treatment periods. Moreover, the model can be transformed into a piecewise linear ordinary differential equation model by introducing three new volume variables, and the study of the resulting model may help to devise optimal IAS schedules.

  10. Singlet oxygen explicit dosimetry to predict long-term local tumor control for Photofrin-mediated photodynamic therapy

    Science.gov (United States)

    Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    Although photodynamic therapy (PDT) is an established modality for the treatment of cancer, current dosimetric quantities do not account for the variations in PDT oxygen consumption for different fluence rates (φ). In this study we examine the efficacy of reacted singlet oxygen concentration ([1O2]rx) to predict long-term local control rate (LCR) for Photofrin-mediated PDT. Radiation-induced fibrosarcoma (RIF) tumors in the right shoulders of female C3H mice are treated with different in-air fluences of 225-540 J/cm2 and in-air fluence rate (φair) of 50 and 75 mW/cm2 at 5 mg/kg Photofrin and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 630 nm wavelength. [1O2]rx is calculated by using a macroscopic model based on explicit dosimetry of Photofrin concentration, tissue optical properties, tissue oxygenation and blood flow changes during PDT. The tumor volume of each mouse is tracked for 90 days after PDT and Kaplan-Meier analyses for LCR are performed based on a tumor volume defined as a temporal integral of photosensitizer concentration and Φ at a 3 mm tumor depth. φ is calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. Our preliminary studies show that [1O2]rx is the best dosimetric quantity that can predict tumor response and correlate with LCR. Moreover, [1O2]rx calculated using the blood flow changes was in agreement with [1O2]rx calculated based on the actual tissue oxygenation.

  11. Impact of Therapy Sequence with Alkylating Agents and MGMT Status in Patients with Advanced Neuroendocrine Tumors.

    Science.gov (United States)

    Krug, Sebastian; Boch, Michael; Rexin, Peter; Gress, Thomas M; Michl, Patrick; Rinke, Anja

    2017-05-01

    Alkylating chemotherapeutics with either a streptozotocin-(STZ) or temozolomide-(TEM) backbone are routinely used in patients with progressive and unresectable pancreatic neuroendocrine tumors (PNET). In addition, dacarbazine (DTIC) was described as an alternative alkylating therapy option for PNETs. The optimal treatment sequence with alkylating compounds and a potential use of O6-methylguanine-DNA methyltransferase (MGMT) level as predictive biomarker have not yet been sufficiently elucidated. The aim of our study was the evaluation of therapy sequence with either STZ-based treatment followed by DTIC (group A) or the inverse schedule with upfront DTIC (group B) and to correlate MGMT status with clinicopathological characteristics and response to therapy. We retrospectively analyzed 28 patients with neuroendocrine tumors (NET) who were treated with STZ-based therapy and DTIC. Additionally, in a second group MGMT immunohistochemistry was performed from primary and metastatic tumor sites. For statistical evaluation Kaplan-Meier analysis, Cox regression methods and Fisher's exact test were used. There was no difference of objective response and disease control between either STZ-based therapy followed by DTIC treatment (group A) after progression or the reverse sequence (group B). Median time to progression (TTP) was estimated to be 21 months in both arms. First-line STZ-based chemotherapy was not superior to first-line DTIC treatment (16 vs. 13 months; p=0.8). MGMT status did not correlate with clinicopathological characteristics or response to therapy with these alkylating agents. Upfront chemotherapy with either STZ-based treatment or DTIC monotherapy showed similar efficacy and median TTP rates. In this study, MGMT protein expression assessed by immunohistochemistry did not play an important role as a predictive marker for alkylating agents. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. [Radiofrequency ablation as a palliative therapy option in ENT tumors: in vivo and in vitro testing].

    Science.gov (United States)

    Bucher, S; Hornung, J; Bonkowsky, V; Iro, H; Zenk, J

    2010-04-01

    High frequency thermotherapy (HFTT) is an established palliative therapy for hepatic malignancies. An in vivo and in vitro trial examined the preconditions for the application of HFTT with liquid-cooled wet electrodes for minimally invasive palliation of head and neck tumors. HFTT was applied with needle electrodes, cooled with isotonic saline solution, and a high-frequency generator (Elektrotom HiTT 106, Berchtold, Tuttlingen) to porcine tongue and narcotized, juvenile domestic pigs to the tongue and neck, and monitored in realtime by B-mode ultrasound. The direction of spread of the hyperthermic zone is well observed using ultrasound. Determining the direction of spread is not possible with cooled-tip electrode needles. Severe complications were not observed during the application. RFA with liquid-cooled needle applicators is not safely applicable for the therapy of head and neck tumors.

  13. Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3)

    International Nuclear Information System (INIS)

    Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

    1988-01-01

    Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF 1 mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free. (author)

  14. 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.

  15. Photodynamic therapy on spontaneous tumors of dogs and cats: a ten-year study

    Science.gov (United States)

    Fonda, Diego

    1992-06-01

    Since 1981, more than fifty spontaneous tumors of dogs and cats were treated by photodynamic therapy with hematoporphyrins in the surgery department of the University of Milan. Therapeutic results proved to be successful and promising in certain forms of cancer and will be compared in the future with the effectiveness of other photosensitizer drugs like phatolocyanines derivatives. Applied hematoporphyrins phototherapy methods included: (1) injection of hematoporphyrins derivative (HpD) and irradiation with laser light at 631 nanometers, using a Rhodamine B dye laser; (2) injection of the active component of hematoporphyrin derivative (DHE) and irradiation with a Rhodamine B dye laser; and (3) injection of DHE and irradiation with laser light at 628 nanometers using a gold vapor laser. More frequently treated tumor sites were oral and nasal cavities. Other localizations were mucous membranes of the glans and stomach. Nineteen histological types were diagnosed in treated tumors.

  16. Visual outcome, endocrine function and tumor control after fractionated stereotactic radiation therapy of craniopharyngiomas in adults

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Munck Af Rosenschöld, Per; Feldt-Rasmussen, Ulla

    2017-01-01

    BACKGROUND: The purpose of this study was to examine visual outcome, endocrine function and tumor control in a prospective cohort of craniopharyngioma patients, treated with fractionated stereotactic radiation therapy (FSRT). MATERIAL AND METHODS: Sixteen adult patients with craniopharyngiomas were...... eligible for analysis. They were treated with linear accelerator-based FSRT during 1999-2015. In all cases, diagnosis was confirmed by histological analysis. The prescription dose to the tumor was 54 Gy (median, range 48-54) in 1.8 or 2.0 Gy per fraction, and the maximum radiation dose to the optic nerves.......7-13.1) for visual outcome, endocrine function, and tumor control, respectively. RESULTS: Visual acuity impairment was present in 10 patients (62.5%) and visual field defects were present in 12 patients (75%) before FSRT. One patient developed radiation-induced optic neuropathy at seven years after FSRT. Thirteen...

  17. Renal histoarchitectural changes in nevirapine therapy: possible ...

    African Journals Online (AJOL)

    This study investigates the attenuating effect of kolaviron in nevirapine- therapy on the histological structure ... virapine and vitamin C; Group G was given nevirapine and kolaviron ..... may be better explained using stereological techniques in.

  18. Optimum modality for photodynamic therapy of tumors: gels containing liposomes with hydrophobic photosensitizers

    Czech Academy of Sciences Publication Activity Database

    Nekvasil, Miloš; Zadinová, M.; Tahotná, Ludmila; Žáčková, Markéta; Poučková, P.; Ježek, Petr

    2007-01-01

    Roč. 68, č. 5 (2007), s. 235-252 ISSN 0272-4391 R&D Projects: GA MŠk 1P04OE152; GA MPO 2A-1TP1/026; GA MZd NC6564 Institutional research plan: CEZ:AV0Z50110509 Keywords : photodynamic therapy of tumors * liposomal photosensitizer gel * hydroxyl-aluminium phtalocyanine * microfluidizacion Subject RIV: FD - Oncology ; Hematology Impact factor: 0.976, year: 2007

  19. A magazine for the implantation of I-125 seeds in interstitial therapy of cerebral tumors

    International Nuclear Information System (INIS)

    Bockermann, V.; Dieckmann, G.; Lott, H.

    1988-01-01

    A compact magazine has been developed allowing a quick and easy implantation of I-125 seeds in interstitial therapy of intracranial tumors. The magazine is made of steel and has the shape of a right parallelepiped. One seed can be put each time into a movable insert. The magazine is connected to a normal application canula. It is easy to handle and contributes much to radioprotection. (orig.) [de

  20. Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

    OpenAIRE

    Mélanie Saint-Jean; Anne-Chantal Knol; Christelle Volteau; Gaëlle Quéreux; Lucie Peuvrel; Anabelle Brocard; Marie-Christine Pandolfino; Soraya Saiagh; Jean-Michel Nguyen; Christophe Bedane; Nicole Basset-Seguin; Amir Khammari; Brigitte Dréno

    2018-01-01

    Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous ...

  1. 4π Noncoplanar Stereotactic Body Radiation Therapy for Centrally Located or Larger Lung Tumors

    International Nuclear Information System (INIS)

    Dong, Peng; Lee, Percy; Ruan, Dan; Long, Troy; Romeijn, Edwin; Low, Daniel A.; Kupelian, Patrick; Abraham, John; Yang, Yingli; Sheng, Ke

    2013-01-01

    Purpose: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4π planning system. Methods and Materials: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7- to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4π plans, in which a column generation method was used to optimize the beam orientation and the fluence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were minimized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4π without violating dose limits set by the clinical plans. The deliverability of 4π plans was preliminarily tested. Results: Using 4π plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P≤.001), respectively, and R 50 was reduced by more than 50%. Lung V 20 , V 10 , and V 5 were reduced by 64%, 53%, and 32% (P≤.001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4π plans by 12% (P=.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. Conclusions: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modulated arc therapy and static intensity modulated radiation therapy plans, the 4π plans yielded significantly and consistently improved tumor coverage and

  2. 4π Noncoplanar Stereotactic Body Radiation Therapy for Centrally Located or Larger Lung Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Peng; Lee, Percy; Ruan, Dan [Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California (United States); Long, Troy; Romeijn, Edwin [Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, Michigan (United States); Low, Daniel A.; Kupelian, Patrick; Abraham, John; Yang, Yingli [Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California (United States); Sheng, Ke, E-mail: ksheng@mednet.ucla.edu [Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California (United States)

    2013-07-01

    Purpose: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4π planning system. Methods and Materials: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7- to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4π plans, in which a column generation method was used to optimize the beam orientation and the fluence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were minimized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4π without violating dose limits set by the clinical plans. The deliverability of 4π plans was preliminarily tested. Results: Using 4π plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P≤.001), respectively, and R{sub 50} was reduced by more than 50%. Lung V{sub 20}, V{sub 10}, and V{sub 5} were reduced by 64%, 53%, and 32% (P≤.001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4π plans by 12% (P=.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. Conclusions: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modulated arc therapy and static intensity modulated radiation therapy plans, the 4π plans yielded significantly and consistently improved tumor

  3. 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

  4. Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.

    Directory of Open Access Journals (Sweden)

    Jianqing Pan

    Full Text Available Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373. Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.

  5. Inhibition of NF-κB in Tumor Cells Exacerbates Immune Cell Activation Following Photodynamic Therapy

    Science.gov (United States)

    Broekgaarden, Mans; Kos, Milan; Jurg, Freek A.; van Beek, Adriaan A.; van Gulik, Thomas M.; Heger, Michal

    2015-01-01

    Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT with inhibitors of PDT-induced survival pathways. In this respect, the transcription factor nuclear factor κB (NF-κB) has been identified as a potential pharmacological target, albeit inhibition of NF-κB may concurrently dampen the subsequent anti-tumor immune response required for complete tumor eradication and abscopal effects. In contrast to these postulations, this study demonstrated that siRNA knockdown of NF-κB in murine breast carcinoma (EMT-6) cells increased survival signaling in these cells and exacerbated the inflammatory response in murine RAW 264.7 macrophages. These results suggest a pro-death and immunosuppressive role of NF-κB in PDT-treated cells that concurs with a hyperstimulated immune response in innate immune cells. PMID:26307977

  6. Composite Configuration Interventional Therapy Robot for the Microwave Ablation of Liver Tumors

    Science.gov (United States)

    Cao, Ying-Yu; Xue, Long; Qi, Bo-Jin; Jiang, Li-Pei; Deng, Shuang-Cheng; Liang, Ping; Liu, Jia

    2017-11-01

    The existing interventional therapy robots for the microwave ablation of liver tumors have a poor clinical applicability with a large volume, low positioning speed and complex automatic navigation control. To solve above problems, a composite configuration interventional therapy robot with passive and active joints is developed. The design of composite configuration reduces the size of the robot under the premise of a wide range of movement, and the robot with composite configuration can realizes rapid positioning with operation safety. The cumulative error of positioning is eliminated and the control complexity is reduced by decoupling active parts. The navigation algorithms for the robot are proposed based on solution of the inverse kinematics and geometric analysis. A simulation clinical test method is designed for the robot, and the functions of the robot and the navigation algorithms are verified by the test method. The mean error of navigation is 1.488 mm and the maximum error is 2.056 mm, and the positioning time for the ablation needle is in 10 s. The experimental results show that the designed robot can meet the clinical requirements for the microwave ablation of liver tumors. The composite configuration is proposed in development of the interventional therapy robot for the microwave ablation of liver tumors, which provides a new idea for the structural design of medical robots.

  7. The role of stereotactic radiation therapy in the management of children with brain tumors.

    Science.gov (United States)

    Lew, C M; LaVally, B

    1995-10-01

    Conventional radiation therapy plays an important role in the management of intracranial tumors in children. For certain tumors radiation therapy serves as the primary mode of treatment, and for others it plays an adjuvant role with surgery and/or chemotherapy. Improvements in long-term survival rates have focused attention on the long-term sequelae of brain tumors and their treatment, and the sequelae, in turn, have become important targets for clinical investigation. Long-term side effects of particular concern in children include cranial nerve damage, memory and intellectual deficits, pituitary-hypothalamic dysfunction, demyelinization of brain tissue, and secondary malignancies. A new form of radiation therapy, stereotactic radiotherapy (SRT), merges the technologies of stereotactic surgery and conventional fractionated radiotherapy. The intent is to deliver maximum tumoricidal doses to the target while limiting the dose to normal surrounding brain tissue. The key feature of SRT is a noninvasive, relocatable immobilization system to assure accurate and reproducible positioning during planning and treatment. The headframes used for children have been modified to address their specific needs. The complexities of this process require careful preparation of patients and their families and the participation of many disciplines. Long-term follow-up will be essential to evaluate the effectiveness of this innovative treatment.

  8. Boron neutron capture therapy of malignant brain tumors at the Brookhaven Medical Research Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Joel, D.D.; Coderre, J.A.; Chanana, A.D. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.

    1996-12-31

    Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope {sup 10}B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/{sup 10}B reactions ({sup 10}B(n,{alpha}){sup 7}Li) resulting in the production of localized high LET radiation from alpha and {sup 7}Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released is microscopically confined to the vicinity of the boron-containing compound. In principal it should be possible with BNCT to selectively destroy small nests or even single cancer cells located within normal tissue. It follows that the major improvements in this form of radiation therapy are going to come largely from the development of boron compounds with greater tumor selectivity, although there will certainly be advances made in neutron beam quality as well as the possible development of alternative sources of neutron beams, particularly accelerator-based epithermal neutron beams.

  9. Boron neutron capture therapy of malignant brain tumors at the Brookhaven Medical Research Reactor

    International Nuclear Information System (INIS)

    Joel, D.D.; Coderre, J.A.; Chanana, A.D.

    1996-01-01

    Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope 10 B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/ 10 B reactions ( 10 B(n,α) 7 Li) resulting in the production of localized high LET radiation from alpha and 7 Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released is microscopically confined to the vicinity of the boron-containing compound. In principal it should be possible with BNCT to selectively destroy small nests or even single cancer cells located within normal tissue. It follows that the major improvements in this form of radiation therapy are going to come largely from the development of boron compounds with greater tumor selectivity, although there will certainly be advances made in neutron beam quality as well as the possible development of alternative sources of neutron beams, particularly accelerator-based epithermal neutron beams

  10. Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model.

    Science.gov (United States)

    Takahashi, Junko; Murakami, Mami; Mori, Takashi; Iwahashi, Hitoshi

    2018-02-09

    Combined treatment with 5-aminolevulinic acid (5-ALA) and X-rays improves tumor suppression in vivo. This is because the accumulated protoporphyrin IX from 5-ALA enhances the generation of ROS by the X-ray irradiation. In the present study, a high-energy medical linear accelerator was used instead of a non-medical low energy X-ray irradiator, which had been previously used. Tumor-bearing mice implanted with B16-BL6 melanoma cells were treated with fractionated doses of irradiation (in total, 20 or 30 Gy), using two types of X-ray irradiator after 5-ALA administration. Suppression of tumor growth was enhanced with X-ray irradiation in combination with 5-ALA treatment compared with X-ray treatment alone, using both medical and non-medical X-ray irradiators. 5-ALA has been used clinically for photodynamic therapy. Thus, "radiodynamic therapy", using radiation from medical linacs as a physical driving force, rather than the light used in photodynamic therapy, may have potential clinical applications.

  11. Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

    International Nuclear Information System (INIS)

    McGovern, Susan L.; Okcu, M. Fatih; Munsell, Mark F.; Kumbalasseriyil, Nancy; Grosshans, David R.; McAleer, Mary F.; Chintagumpala, Murali; Khatua, Soumen; Mahajan, Anita

    2014-01-01

    Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials: The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results: Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions: This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted

  12. Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

    Energy Technology Data Exchange (ETDEWEB)

    McGovern, Susan L., E-mail: slmcgove@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Okcu, M. Fatih [Texas Children' s Hematology and Oncology Centers, Department of Pediatrics, Baylor College of Medicine, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kumbalasseriyil, Nancy; Grosshans, David R.; McAleer, Mary F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chintagumpala, Murali [Texas Children' s Hematology and Oncology Centers, Department of Pediatrics, Baylor College of Medicine, Houston, Texas (United States); Khatua, Soumen [Department of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-12-01

    Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials: The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results: Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions: This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted.

  13. Study on medical economic evaluation methods for metastatic brain tumors therapy

    International Nuclear Information System (INIS)

    Takura, Tomoyuki; Hayashi, Motohiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Uetsuka, Yoshio

    2010-01-01

    Treatment design for metastatic brain tumors is required to firstly care about the life and function for which the patient hopes because it is terminal care. Therefore, to discuss the value of the therapy, a viewpoint of the quality of life (QOL) and the socioeconomic factors other than the survival rate is important. However, examination that applies these factors to the therapy needs to be carried out more thoroughly. With this in mind, we discuss cost effectiveness of therapy for metastatic brain tumor, through a pilot study on gamma knife therapy. We studied 18 patients (mean age 61.6 years old) undergoing therapy for metastatic brain tumors. The health rate QOL was assessed by the profile-type measure SF-36 (Short-Form 36-Item Ver1.2) and the preference-based measure EQ-5D (EuroQoL-5D), before and six months after gamma knife therapy. Cost-utility-analysis (yen/Qaly) was carried out from quality adjusted life years (Qalys) and medical fee claims. In addition, we made a correlation analysis of the irradiation procedure and the gains attained. The observation by SF-36 for six months was useful for metastatic brain tumor. As a result, the QOL indicators showed increased mental health (MH: p=0.040) and role emotional (RE: p=0.029) with significant difference. In the measurement of EQ-5D, it was added only for one month based on the significant difference (p=0.022) from the pre-therapy QOL. The utilities that were analyzed became 0.052±0.175 standard deviation (SD) (score), and Qalys were 0.135. Because the cost was 721.4±5.2 SD (thousand yen), the performance of cost-utility-analysis was estimated as 5,330,000 (yen/Qaly). In addition, positive correlation (r=0.845/p=0.034) was found between the EQ-5D utility score and the tumor irradiation energy (mJ), etc. We established a new value over and above mere survival rate concerning metastatic brain tumor therapy. The socioeconomics and efficacy of therapy are more difficult to discuss in this disease than in other

  14. Stereotactic Body Radiation Therapy for Patients with Heavily Pretreated Liver Metastases and Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lanciano, Rachelle; Lamond, John; Yang, Jun; Feng, Jing; Arrigo, Steve; Good, Michael; Brady, Luther, E-mail: rlancmd@gmail.com [Philadelphia CyberKnife, Drexel University, Havertown, PA (United States)

    2012-03-09

    We present our initial experience with CyberKnife stereotactic body radiation therapy (SBRT) in a heavily pretreated group of patients with liver metastases and primary liver tumors. From October 2007 to June 2009, 48 patients were treated at the Philadelphia CyberKnife Center for liver metastases or primary liver tumors. We report on 30 patients with 41 discrete lesions (1–4 tumors per patient) who received an ablative radiation dose (BED ≥ 79.2 Gy10 = 66 Gy EQD2). The treatment goal was to achieve a high SBRT dose to the liver tumor while sparing at least 700 cc of liver from radiation doses above 15 Gy. Twenty-three patients were treated with SBRT for metastatic cancer to the liver; the remainder (n = 7) were primary liver tumors. Eighty-seven percent of patients had prior systemic chemotherapy with a median 24 months from diagnosis to SBRT; 37% had prior liver directed therapy. Local control was assessed for 28 patients (39 tumors) with 4 months or more follow-up. At a median follow-up of 22 months (range, 10–40 months), 14/39 (36%) tumors had documented local failure. A decrease in local failure was found with higher doses of SBRT (p = 0.0237); 55% of tumors receiving a BED ≤ 100 Gy10 (10/18) had local failure compared with 19% receiving a BED > 100 Gy10 (4/21). The 2-year actuarial rate of local control for tumors treated with BED > 100 Gy10 was 75% compared to 38% for those patients treated with BED ≤ 100 Gy10 (p = 0.04). At last follow-up, 22/30 patients (73%) had distant progression of disease. Overall, seven patients remain alive with a median survival of 20 months from treatment and 57 months from diagnosis. To date, no patient experienced persistent or severe adverse effects. Despite the heavy pretreatment of these patients, SBRT was well tolerated with excellent local control rates when adequate doses (BED > 100 Gy10) were used. Median survival was limited secondary to development of further metastatic disease in the majority of patients.

  15. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    Energy Technology Data Exchange (ETDEWEB)

    Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  16. TH-A-BRF-02: BEST IN PHYSICS (JOINT IMAGING-THERAPY) - Modeling Tumor Evolution for Adaptive Radiation Therapy

    International Nuclear Information System (INIS)

    Liu, Y; Lee, CG; Chan, TCY; Cho, YB; Islam, MK

    2014-01-01

    Purpose: To develop mathematical models of tumor geometry changes under radiotherapy that may support future adaptive paradigms. Methods: A total of 29 cervical patients were scanned using MRI, once for planning and weekly thereafter for treatment monitoring. Using the tumor volumes contoured by a radiologist, three mathematical models were investigated based on the assumption of a stochastic process of tumor evolution. The “weekly MRI” model predicts tumor geometry for the following week from the last two consecutive MRI scans, based on the voxel transition probability. The other two models use only the first pair of consecutive MRI scans, and the transition probabilities were estimated via tumor type classified from the entire data set. The classification is based on either measuring the tumor volume (the “weekly volume” model), or implementing an auxiliary “Markov chain” model. These models were compared to a constant volume approach that represents the current clinical practice, using various model parameters; e.g., the threshold probability β converts the probability map into a tumor shape (larger threshold implies smaller tumor). Model performance was measured using volume conformity index (VCI), i.e., the union of the actual target and modeled target volume squared divided by product of these two volumes. Results: The “weekly MRI” model outperforms the constant volume model by 26% on average, and by 103% for the worst 10% of cases in terms of VCI under a wide range of β. The “weekly volume” and “Markov chain” models outperform the constant volume model by 20% and 16% on average, respectively. They also perform better than the “weekly MRI” model when β is large. Conclusion: It has been demonstrated that mathematical models can be developed to predict tumor geometry changes for cervical cancer undergoing radiotherapy. The models can potentially support adaptive radiotherapy paradigm by reducing normal tissue dose. This research

  17. TH-A-BRF-02: BEST IN PHYSICS (JOINT IMAGING-THERAPY) - Modeling Tumor Evolution for Adaptive Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Y; Lee, CG [University of Toronto, Toronto, ON (Canada); Chan, TCY [University of Toronto, Toronto, ON (Canada); Techna Institute for the Advancement of Technology for Health, Toronto, ON (Canada); Cho, YB; Islam, MK [University of Toronto, Toronto, ON (Canada); Princess Margaret Hospital, Toronto, ON (Canada); Ontario Consortium for Adaptive Interventions in Radiation Oncology (OCAIRO) (Canada)

    2014-06-15

    Purpose: To develop mathematical models of tumor geometry changes under radiotherapy that may support future adaptive paradigms. Methods: A total of 29 cervical patients were scanned using MRI, once for planning and weekly thereafter for treatment monitoring. Using the tumor volumes contoured by a radiologist, three mathematical models were investigated based on the assumption of a stochastic process of tumor evolution. The “weekly MRI” model predicts tumor geometry for the following week from the last two consecutive MRI scans, based on the voxel transition probability. The other two models use only the first pair of consecutive MRI scans, and the transition probabilities were estimated via tumor type classified from the entire data set. The classification is based on either measuring the tumor volume (the “weekly volume” model), or implementing an auxiliary “Markov chain” model. These models were compared to a constant volume approach that represents the current clinical practice, using various model parameters; e.g., the threshold probability β converts the probability map into a tumor shape (larger threshold implies smaller tumor). Model performance was measured using volume conformity index (VCI), i.e., the union of the actual target and modeled target volume squared divided by product of these two volumes. Results: The “weekly MRI” model outperforms the constant volume model by 26% on average, and by 103% for the worst 10% of cases in terms of VCI under a wide range of β. The “weekly volume” and “Markov chain” models outperform the constant volume model by 20% and 16% on average, respectively. They also perform better than the “weekly MRI” model when β is large. Conclusion: It has been demonstrated that mathematical models can be developed to predict tumor geometry changes for cervical cancer undergoing radiotherapy. The models can potentially support adaptive radiotherapy paradigm by reducing normal tissue dose. This research

  18. Inhibition of hypoxia-inducible factor 1 with acriflavine sensitizes hypoxic tumor cells to photodynamic therapy with zinc phthalocyanine-encapsulating cationic liposomes

    NARCIS (Netherlands)

    Broekgaarden, Mans; Weijer, Ruud; Krekorian, Massis; van den IJssel, Bas; Kos, Milan; Alles, Lindy K.; van Wijk, Albert C.; Bikadi, Zsolt; Hazai, Eszter; van Gulik, Thomas M.; Heger, Michal

    2016-01-01

    Photodynamic therapy (PDT) is a tumor treatment modality in which a tumorlocalized photosensitizer is excited with light, which results in local production of reactive oxygen species, destruction of tumor vasculature, tumor hypoxia, tumor cell death, and induction of an anti-tumor immune response.

  19. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    International Nuclear Information System (INIS)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-01-01

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  20. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

    2015-10-15

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  1. Measuring Response to Therapy by Near-Infrared Imaging of Tumors Using a Phosphatidylserine-Targeting Antibody Fragment

    Directory of Open Access Journals (Sweden)

    Jian Gong

    2013-06-01

    Full Text Available Imaging tumors and their response to treatment could be a valuable biomarker toward early assessment of therapy in patients with cancer. Phosphatidylserine (PS is confined to the inner leaflet of the plasma membrane in normal cells but is externalized on tumor vascular endothelial cells (ECs and tumor cells, and PS exposure is further enhanced in response to radiation and chemotherapy. In the present study, we evaluated the potential of a PS-targeting human F(ab'2 antibody fragment, PGN650, to detect exposure of PS in tumor-bearing mice. Tumor uptake of PGN650 was measured by near-infrared optical imaging in human tumor xenografts in immunodeficient mice. PGN650 specifically targeted tumors and was shown to target CD31-positive ECs and tumor cells. Tumor uptake of PGN650 was significantly higher in animals pretreated with docetaxel. The peak tumor to normal tissue (T/N ratio of probe was observed at 24 hours postinjection of probe, and tumor binding was detected for at least 120 hours. In repeat dose studies, PGN650 uptake in tumors was significantly higher following pretreatment with docetaxel compared to baseline uptake prior to treatment. PGN650 may be a useful probe to detect PS exposed in tumors and to monitor enhanced PS exposure to optimize therapeutic agents to treat tumors.

  2. A metastatic adrenal tumor from a hepatocellular carcinoma: combination therapy with transarterial chemoembolization and radiofrequency ablation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyun Jin; Cho, Yun Ku; Ahn, Yong Sik; Kim, Mi Young [Seoul Veterans Hospital, Seoul (Korea, Republic of)

    2007-07-15

    The adrenal gland is the second most common site of metastasis from a hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) for these tumors has been reported to be a potentially effective alternative to an adrenalectomy, especially for inoperable patients. However, for intermediate or large adrenal tumors, combination therapy of transarterial chemoembolization (TACE) and RFA can be attempted as it may reduce the heat sink effect. A 74-year-old patient presented with abdominal discomfort. Abdominal CT images revealed a 5.0 cm sized right adrenal mass. A percutaneous biopsy of the adrenal mass revealed a metastatic hepatocellular carcinoma. TACE was performed on the adrenal mass. However, a one-month follow-up CT image revealed a residual viable tumor. RFA was performed for the adrenal tumor six weeks after the TACE. No procedure-related major complications were noted. The serum alpha-fetoprotein level had also been normalized after the treatment, and 10-month follow-up CT images showed no definite evidence of viable adrenal tumor.

  3. In ovo method for evaluating the effect of nutritional therapies on tumor development, growth and vascularization

    Directory of Open Access Journals (Sweden)

    Yves M. Dupertuis

    2015-10-01

    Full Text Available In the state of the art evaluation of nutritional therapy on tumor development, growth and vascularization requires tedious and expensive in vivo assays in which a significant number of animals undergo invasive treatments. Therefore, new alternative methods to avoid animal suffering and sacrifice are welcome. This review presents a rapid and low-cost method of experimental radio/chemotherapy in tumor xenografted chicken chorioallantoic membrane (CAM, which may contribute to implement the 3R principle (Reduce, Refine, Replace. Advantages and limitations of the CAM as an experimental model in cancer research are discussed. Improving the CAM model by using tumor spheroid grafting and positron emission and computed tomography imaging would help to overcome the drawbacks of poor tumor grafting efficiency and restrained 2-D tumor growth measurement to the CAM surface. Such a simple, reliable, reproducible and quantitative method for obtaining dose–response analysis and estimating treatment schedule (i.e. type, route, dose and timing would provide an alternative to the time-consuming and expensive evaluation step in animals before initiating clinical trials.

  4. Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

    Science.gov (United States)

    Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

    2017-02-01

    This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume <=100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

  5. Radiobiological studies on the importance of tumor oxygenation for anti-neoplastic therapy

    International Nuclear Information System (INIS)

    Grau, C.

    1994-01-01

    The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD 50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

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

    Science.gov (United States)

    Silk, Ann W; Schuetze, Scott M

    2012-09-01

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

  7. Radiation therapy for primary carcinoma of the eyelid. Tumor control and visual function

    Energy Technology Data Exchange (ETDEWEB)

    Hata, M.; Koike, I.; Odagiri, K.; Kasuya, T.; Minagawa, Y.; Kaizu, H.; Mukai, Y.; Inoue, T. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Radiology; Maegawa, J. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Plastic and Reconstructive Surgery; Kaneko, A. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Ophthalmology

    2012-12-15

    Background and purpose: Surgical excision remains the standard and most reliable curative treatment for eyelid carcinoma, but frequently causes functional and cosmetic impairment of the eyelid. We therefore investigated the efficacy and safety of radiation therapy in eyelid carcinoma. Patients and methods: Twenty-three patients with primary carcinoma of the eyelid underwent radiation therapy. Sebaceous carcinoma was histologically confirmed in 16 patients, squamous cell carcinoma in 6, and basal cell carcinoma in 1. A total dose of 50-66.6 Gy (median, 60 Gy) was delivered to tumor sites in 18-37 fractions (median, 30 fractions). Results: All but 3 of the 23 patients had survived at a median follow-up period of 49 months. The overall survival and local progression-free rates were 87% and 93% at 2 years, and 80% and 93% at 5 years, respectively. Although radiation-induced cataracts developed in 3 patients, visual acuity in the other patients was relatively well preserved. There were no other therapy-related toxicities of grade 3 or greater. Conclusion: Radiation therapy is safe and effective for patients with primary carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid. (orig.)

  8. Vasculatures in Tumors Growing From Preirradiated Tissues: Formed by Vasculogenesis and Resistant to Radiation and Antiangiogenic Therapy

    International Nuclear Information System (INIS)

    Chen, Fang-Hsin; Chiang, Chi-Shiun; Wang, Chun-Chieh; Fu, Sheng-Yung; Tsai, Chien-Sheng; Jung, Shih-Ming; Wen, Chih-Jen; Lee, Chung-Chi; Hong, Ji-Hong

    2011-01-01

    Purpose: To investigate vasculatures and microenvironment in tumors growing from preirradiated tissues (pre-IR tumors) and study the vascular responses of pre-IR tumors to radiation and antiangiogenic therapy. Methods and Materials: Transgenic adenocarcinoma of the mouse prostate C1 tumors were implanted into unirradiated or preirradiated tissues and examined for vascularity, hypoxia, and tumor-associated macrophage (TAM) infiltrates by immunohistochemistry. The origin of tumor endothelial cells was studied by green fluorescent protein-tagged bone marrow (GFP-BM) transplantation. The response of tumor endothelial cells to radiation and antiangiogenic agent was evaluated by apoptotic assay. Results: The pre-IR tumors had obvious tumor bed effects (TBE), with slower growth rate, lower microvascular density (MVD), and more necrotic and hypoxic fraction compared with control tumors. The vessels were dilated, tightly adhered with pericytes, and incorporated with transplanted GFP-BM cells. In addition, hypoxic regions became aggregated with TAM. As pre-IR tumors developed, the TBE was overcome at the tumor edge where the MVD increased, TAM did not aggregate, and the GFP-BM cells did not incorporate into the vessels. The vessels at tumor edge were more sensitive to the following ionizing radiation and antiangiogenic agent than those in the central low MVD regions. Conclusions: This study demonstrates that vasculatures in regions with TBE are mainly formed by vasculogenesis and resistant to radiation and antiangiogenic therapy. Tumor bed effects could be overcome at the edge of larger tumors, but where vasculatures are formed by angiogenesis and sensitive to both treatments. Vasculatures formed by vasculogenesis should be the crucial target for the treatment of recurrent tumors after radiotherapy.

  9. Dose comparison according to Smooth Thickness application of Range compensator during proton therapy for brain tumor patient

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tase Woan; Kim, Dae Woong; Kim, Jae Weon; Jeong, Kyeong Sik [Proton Therapy Center, National Cancer Center, Goyang (Korea, Republic of)

    2016-12-15

    Range Compensator used for proton therapy compensates the proton beam dose which delivers to the normal tissues according to the Target's Distal Margin dose. We are going to check the improvement of dose on the target part by comparing the dose of PTV and OAR according to applying in different method of Smooth Thickness of Range Compensator which is used in brain tumor therapy. For 10 brain tumor patients taking proton therapy in National Cancer Center, Apply Smooth Thickness applied in Range Compensator in order from one to five by using Compensator Editor of Eclipse Proton Planning System(Version 10.0, Varian, USA). The therapy plan algorithm used Proton Convolution Superposition(version 8.1.20 or 10.0.28), and we compared Dmax, Dmin, Homogeneity Index, Conformity Index and OAR dose around tumor by applying Smooth Thickness in phase. When Smooth Thickness was applied from one to five, the Dmax of PTV was decreased max 4.3%, minimum at 0.8 and average of 1.81%. Dmin increased max 1.8%, min 1.8% and average. Difference between max dose and minimum dose decreased at max 5.9% min 1.4% and average 2.6%. Homogeneity Index decreased average of 0.018 and Conformity Index didn't had a meaningful change. OAR dose decreased in Brain Stem at max 1.6%, min 0.1% and average 0.6% and in Optic Chiasm max 1.3%, min 0.3%, and average 0.5%. However, patient C and patient E had an increase each 0.3% and 0.6%. Additionally, in Rt. Optic Nerve, there was a decrease at max 1.5%, min 0.3%, and average 0.8%, however, patient B had 0.1% increase. In Lt. Optic Nerve, there was a decrease at max 1.8%, min 0.3%, and average 0.7%, however, patient H had 0.4 increase. As Smooth Thickness of Range Compensator which is used as the proton treatment for brain tumor patients is applied in stages, the resolution of Compensator increased and as a result the most optimized amount of proton beam dose can be delivered. This is considered to be able to irradiate the equal amount at PTV and

  10. Long-term prognosis of maxillary sinus malignant tumor patients treated by fast neutron radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Hirohisa; Numata, Tsutomu; Yuza, Jun; Suzuki, Haruhiko; Konno, Akiyoshi [Chiba Univ. (Japan). School of Medicine; Miyamoto, Tadaaki

    1995-03-01

    From 1976 through 1990, 19 patients with maxillary sinus malignant tumor were treated with combination therapy consisting of maxillectomy and radiation of fast neutron. Fast neutron radiotherapy was performed at National Institute of Radiological Sciences. Eight patients had adenoid cystic carcinomas, three patients squamous cell carcinomas, one patient a carcinoma in pleomorphic adenoma, four patients fibrosarcomas, one patient osteosarcoma, one patient chondrosarcoma and one patient rhabdomyosarcoma. Fast neutron therapy after/before surgery was effective in fresh cases with T2-3N0M0 adenoid cystic carcinomas and sarcomas (except for fibrosarcoma). Nine patients were alive more than three years after treatment. And serious complications of fast neutron radiation therapy appeared in six of these nine patients. Visual impairment of opposite side occurred in four patients. Bone necrosis occured in one patient and brain dysfunction in one patient. (author).

  11. Long-term prognosis of maxillary sinus malignant tumor patients treated by fast neutron radiation therapy

    International Nuclear Information System (INIS)

    Kishi, Hirohisa; Numata, Tsutomu; Yuza, Jun; Suzuki, Haruhiko; Konno, Akiyoshi; Miyamoto, Tadaaki.

    1995-01-01

    From 1976 through 1990, 19 patients with maxillary sinus malignant tumor were treated with combination therapy consisting of maxillectomy and radiation of fast neutron. Fast neutron radiotherapy was performed at National Institute of Radiological Sciences. Eight patients had adenoid cystic carcinomas, three patients squamous cell carcinomas, one patient a carcinoma in pleomorphic adenoma, four patients fibrosarcomas, one patient osteosarcoma, one patient chondrosarcoma and one patient rhabdomyosarcoma. Fast neutron therapy after/before surgery was effective in fresh cases with T2-3N0M0 adenoid cystic carcinomas and sarcomas (except for fibrosarcoma). Nine patients were alive more than three years after treatment. And serious complications of fast neutron radiation therapy appeared in six of these nine patients. Visual impairment of opposite side occurred in four patients. Bone necrosis occured in one patient and brain dysfunction in one patient. (author)

  12. Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

    Directory of Open Access Journals (Sweden)

    Way-Seah Lee

    2017-10-01

    Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

  13. Macrophage membrane-coated iron oxide nanoparticles for enhanced photothermal tumor therapy

    Science.gov (United States)

    Meng, Qian-Fang; Rao, Lang; Zan, Minghui; Chen, Ming; Yu, Guang-Tao; Wei, Xiaoyun; Wu, Zhuhao; Sun, Yue; Guo, Shi-Shang; Zhao, Xing-Zhong; Wang, Fu-Bing; Liu, Wei

    2018-04-01

    Nanotechnology possesses the potential to revolutionize the diagnosis and treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy should have long blood circulation times and active cancer targeting. Additionally, they should be harmless and invisible to the immune system. Here, we developed a biomimetic nanoplatform with the above properties for cancer therapy. Macrophage membranes were reconstructed into vesicles and then coated onto magnetic iron oxide nanoparticles (Fe3O4 NPs). Inherited from the Fe3O4 core and the macrophage membrane shell, the resulting Fe3O4@MM NPs exhibited good biocompatibility, immune evasion, cancer targeting and light-to-heat conversion capabilities. Due to the favorable in vitro and in vivo properties, biomimetic Fe3O4@MM NPs were further used for highly effective photothermal therapy of breast cancer in nude mice. Surface modification of synthetic nanomaterials with biomimetic cell membranes exemplifies a novel strategy for designing an ideal nanoplatform for translational medicine.

  14. Electrophysiological Monitoring in Patients With Tumors of the Skull Base Treated by Carbon-12 Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Carozzo, Simone [Department of Neuroscience, Ophthalmology, and Genetics, University of Genova, Genova (Italy); Schardt, Dieter [Department of Biophysics, GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt (Germany); Narici, Livio [Department of Physics, University of Rome Tor Vergata, Rome (Italy); Combs, Stephanie E.; Debus, Jürgen [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany); Sannita, Walter G., E-mail: wgs@dism.unige.it [Department of Neuroscience, Ophthalmology, and Genetics, University of Genova, Genova (Italy); Department of Psychiatry, State University of New York, Stony Brook, New York (United States)

    2013-03-15

    Purpose: To report the results of short-term electrophysiologic monitoring of patients undergoing {sup 12}C therapy for the treatment of skull chordomas and chondrosarcomas unsuitable for radical surgery. Methods and Materials: Conventional electroencephalogram (EEG) and retinal and cortical electrophysiologic responses to contrast stimuli were recorded from 30 patients undergoing carbon ion radiation therapy, within a few hours before the first treatment and after completion of therapy. Methodologies and procedures were compliant with the guidelines of the International Federation for Clinical Neurophysiology and International Society for Clinical Electrophysiology of Vision. Results: At baseline, clinical signs were reported in 56.6% of subjects. Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical evoked potentials), and 92.8% (electroretinogram) of cases, without correlation with neurologic signs, tumor location, or therapy plan. Results on EEG, but not electroretinograms and cortical responses, were more often abnormal in patients with reported clinical signs. Abnormal EEG results and retinal/cortical responses improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70% (electroretinogram) of cases. Results on EEG worsened after therapy in one-third of patients whose recordings were normal at baseline. Conclusions: The percentages of subjects whose EEG results improved or worsened after therapy and the improvement of retinal/cortical responses in the majority of patients are indicative of a limited or negligible (and possibly transient) acute central nervous system toxicity of carbon ion therapy, with a significant beneficial effect on the visual pathways. Research on large samples would validate electrophysiologic procedures as a possible independent test for central nervous system toxicity and allow investigation of the correlation with clinical signs; repeated testing over time after therapy would demonstrate, and may

  15. Tumor reoxygenation by aqueous oxygen solutions and its role in cancer treatment with chemotherapy and radiation therapy

    International Nuclear Information System (INIS)

    Calderwood, S.K.

    2003-01-01

    Many tumors contain significant areas of hypoxia which cause resistance to tumor radiation therapy and chemotherapy. We have used perfusion into afferent arteries with super saturated aqueous oxygen solutions (AO) to re-oxygenate the hypoxic areas of experimental tumors with the aim of restoring sensitivity to treatment and enhancing cancer therapy. We first concentrated on examining the ability of AO infusion to reoxygenate the MAT B III 13762 rat carcinoma growing in the thighs of rats. In experiments on 33 AO infused tumors using Eppendorf microelectrode monitoring, we consistently observed a significant decrease in the fraction of tumor domains with O 2 less than 5mmHg before and after AO infusion. Significant tumor reoxygenation was observed in most tumors with a volume less than 2.5 cm 3 . We next examined 15 New Zealand white rabbits transplanted with the VX2 carcinoma. Tissue oxygen studies indicated that intramuscular rabbit VX-2 tumor has a consistently lower hypoxic fraction (O 2 2 <5mm Hg). Significant reoxygenation did occur in these infused tumors although the degree of reoxygenation was slightly less than in the rat MAT B III 13762 perhaps reflecting the lower hypoxic fraction. Further studies showed that AO could also be infused directly into tumors with a reduction of hypoxic fraction of between 60-90% Overall, the experiments show that AO infusion into either arterial or intratumor sites is a viable approach to tumor reoxygenation and preliminary studies indicate increase effectiveness in treatment with cyclophosphamide / AO combination

  16. Cognitive marital therapy : the process of change

    NARCIS (Netherlands)

    Emmelkamp, P.; van Linden van den Heuvell, C.; Sanderman, R.; Scholing, A.

    1988-01-01

    Responds to comments made by N. Epstein and D. H. Baucom (see record 1989-16434-001) concerning the present authors' (see record 1989-16433-001) study of communication skills training and cognitive therapy for distressed couples. The reliable assessment of cognitions in outcome studies is discussed.

  17. Monte Carlo calculation of the maximum therapeutic gain of tumor antivascular alpha therapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chen-Yu; Oborn, Bradley M.; Guatelli, Susanna; Allen, Barry J. [Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, New South Wales 2217 (Australia); Illawarra Cancer Care Centre, Wollongong, New South Wales 2522, Australia and Centre for Medical Radiation Physics, University of Wollongong, New South Wales 2522 (Australia); Centre for Medical Radiation Physics, University of Wollongong, New South Wales 2522 (Australia); Centre for Experimental Radiation Oncology, St. George Clinical School, University of New South Wales, Kogarah, New South Wales 2217 (Australia)

    2012-03-15

    Purpose: Metastatic melanoma lesions experienced marked regression after systemic targeted alpha therapy in a phase 1 clinical trial. This unexpected response was ascribed to tumor antivascular alpha therapy (TAVAT), in which effective tumor regression is achieved by killing endothelial cells (ECs) in tumor capillaries and, thus, depriving cancer cells of nutrition and oxygen. The purpose of this paper is to quantitatively analyze the therapeutic efficacy and safety of TAVAT by building up the testing Monte Carlo microdosimetric models. Methods: Geant4 was adapted to simulate the spatial nonuniform distribution of the alpha emitter {sup 213}Bi. The intraluminal model was designed to simulate the background dose to normal tissue capillary ECs from the nontargeted activity in the blood. The perivascular model calculates the EC dose from the activity bound to the perivascular cancer cells. The key parameters are the probability of an alpha particle traversing an EC nucleus, the energy deposition, the lineal energy transfer, and the specific energy. These results were then applied to interpret the clinical trial. Cell survival rate and therapeutic gain were determined. Results: The specific energy for an alpha particle hitting an EC nucleus in the intraluminal and perivascular models is 0.35 and 0.37 Gy, respectively. As the average probability of traversal in these models is 2.7% and 1.1%, the mean specific energy per decay drops to 1.0 cGy and 0.4 cGy, which demonstrates that the source distribution has a significant impact on the dose. Using the melanoma clinical trial activity of 25 mCi, the dose to tumor EC nucleus is found to be 3.2 Gy and to a normal capillary EC nucleus to be 1.8 cGy. These data give a maximum therapeutic gain of about 180 and validate the TAVAT concept. Conclusions: TAVAT can deliver a cytotoxic dose to tumor capillaries without being toxic to normal tissue capillaries.

  18. Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

    International Nuclear Information System (INIS)

    Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2010-01-01

    Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months ± 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    the tumor motion trajectory and its final locations obtained from simulations with and without considering tissue incompressibility variation were very different. For example, tumor displacements in the z direction were −11.23 and −38.10 mm obtained with the Marlow hyperelastic material model in conjunction with constant and variable Poisson's ratio, respectively. By comparing the acquired 4D-CT image sequence of the porcine lung with their image sequence counterparts obtained from the hyperelastic model with constant and variable Poisson's ratio, it was shown that using variable tissue incompressibility reduced errors significantly in tumor motion prediction. Conclusions: This investigation demonstrates the importance of incompressibility variation estimation and utilization for accurate tumor tracking in computer assisted lung external beam radiation therapy. An optimization framework was developed to estimate a Poisson's ratio function in terms of respiration cycle time using experimental image data of the lung. Utilizing this function along with respiratory system FE modeling may lead to more effective tumor targeting, hence potentially improving the outcome of lung external beam radiation therapy techniques. This is particularly true for stereotactic body radiation therapy where only one or a few fraction treatments are applied, precluding the possibility of averaging out dosimetric deviations introduced by the respiratory motion.

  20. Radiation Therapy for Pituitary Adenoma - Changes in Endocrine Function after Treatment-

    International Nuclear Information System (INIS)

    Yoon, Sei Chul; Jang, Hong Suck; Kim, Song Hwan; Shinn, Kyung Sub; Bahk, Yong Whee; Son, Ho Young; Kang, Joon Ki

    1991-01-01

    Seventy four patients with pituitary adenoma received radiation therapy(RT) on the pituitary area using 6 MV linear accelerator during the past 7 years at the Division of Radiation Therapy, Kangnam St. mary's hospital, Catholic University Medical College. Thirty nine were men and 35 were women. The age ranged from 7 to 65 years with the mean being 37 years. Sixty five (88%) patients were treated postoperatively and 9(12%) primary RT. To evaluate the effects of RT, we analyzed the series of endocrinologic studies with prolactin(PRL), growth hormone(GH), adrenocortiotrophic hormone (ACTH), leuteinizing hormone (LH), follicular stimulating hormone(FSH) and thyroid stimulating hormone(TSH) etc after RT. All but one with Nelson's syndrome showed abnormal neuroradiologic changes in the sella turica with invasive tumor mass around supra-and/or parasella area. The patients were classified as 23(29%) prolactinomas and 20 (26%) growth hormone (GH) secreting tumors, and 6(8%) ACTH secreting ones consisting of 4 Cushing's disease and 2 Nelson's syndrome. Twenty nine(37%) had nonfunctioning tumor and four (5%) of those secreting pituitary tumors were mixed PRL-GH secreting tumors. The hormonal level in 15(65%) of 23 PRL and 3(15%) of 20 GH secreting tumors returned to normal by 2 to 3 years after RT, but five PRL and five GH secreting tumors showed high hormonal level requiring bromocriptine medication. Endocrinologic insufficiency developed by 3 years after RT in 5 of 7 panhypopituitarisms, 4 of seven hypothyroidisms and one of two hypogonadisms, respectively, Fifteen(20%) patients were lost to follow up after RT

  1. Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors

    International Nuclear Information System (INIS)

    Zamenhof, R.G.; Clement, S.D.; Harling, O.K.; Brenner, J.F.; Wazer, D.E.; Madoc-Jones, H.; Yanch, J.C.

    1990-01-01

    Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction

  2. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

    Science.gov (United States)

    Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

    2009-02-01

    Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

  3. Effects of intra-arterial infusion therapy or systemic chemotherapy with docetaxel for VX2 tumor in rabbit hind limb

    International Nuclear Information System (INIS)

    Qian Yuanxin; Wu Xiaomei; He Miao; Liu Tao; Deng Duo

    2010-01-01

    Objective: To discuss the efficacy and safety of intra-arterial infusion therapy with docetaxel. Methods: Animal model of VX2 tumor in rabbit hind limb was set up. Intra-arterial infusion therapy or systemic chemotherapy with docetaxel was performed. Concentrations of docetaxel in VX2 tumor, wall of stomach, liver, kidney and plasma of rabbits with VX2 tumors in hind limbs were determined. Difference of drug concentrations between intra-arterial infusion therapy and systemic chemotherapy was compared using Student t-test. Results: Concentrations of docetaxel in VX2 tumor and wall of stomach of rabbits with intra-arterial infusion therapy were significantly higher than those with systemic chemotherapy (p<0.05). The drug concentration in VX2 tumor of rabbits with intra-arterial infusion was 14 times higher than that with systemic chemotherapy. Concentration of docetaxel in plasma of rabbits with intra-arterial infusion therapy was not significantly lower than that with systemic chemotherapy (P<0.05). Conclusion: Intra-arterial infusion therapy with docetaxel for tumor is effective. However, there is increased risk of toxicity and the dose should adjusted accordingly. (authors)

  4. Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry.

    Science.gov (United States)

    Hörsch, Dieter; Ezziddin, Samer; Haug, Alexander; Gratz, Klaus Friedrich; Dunkelmann, Simone; Krause, Bernd Joachim; Schümichen, Carl; Bengel, Frank M; Knapp, Wolfram H; Bartenstein, Peter; Biersack, Hans-Jürgen; Plöckinger, Ursula; Schwartz-Fuchs, Sabine; Baum, R P

    2013-01-01

    Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9-70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.

  5. Measuring treatment response to systemic therapy and predicting outcome in biliary tract cancer: comparing tumor size, volume, density, and metabolism.

    Science.gov (United States)

    Sahani, Dushyant V; Hayano, Koichi; Galluzzo, Anna; Zhu, Andrew X

    2015-04-01

    The purpose of this study was to evaluate the response of biliary tract cancer treated with multidrug chemotherapy using FDG PET in comparison with morphologic and density changes. In this phase II clinical trial, 28 patients with unresectable or metastatic biliary tract cancers treated with gemcitabine and oxaliplatin combined with bevacizumab (GEMOX-B) underwent FDG PET and contrast-enhanced CT at baseline and after the second cycle of the therapy (8 weeks). A single reviewer recorded tumor maximum standardized uptake value (SUVmax) along with size, volume (3D-sphere), and density. The percentage changes of the parameters were compared with progression-free survival at 7 months. Overall survival was compared with the percentage change of SUVmax. After 8 weeks, measurable reductions (±SD) in size (7.05±4.19 to 5.52±3.28 cm, -21.70%), volume (411.38±540.08 to 212.41±293.45 cm3, -48.36%), and density (60.76±20.65 to 50.68±16.89 HU, -15.59%) were noted along with a substantial drop in SUVmax (5.95±1.95 to 3.36±1.28, -43.52%). The SUVmax change showed positive correlations with tumor size change (R2=0.39, p=0.0004) and volumetric change (R2=0.34, p=0.001). Patients who showed a larger drop in SUVmax at 8 weeks correlated with favorable progression-free survival (p=0.02). ROC analysis showed that a 45% reduction in SUVmax was the best cutoff value to detect favorable progression-free survival patients. When we used this cutoff value, Kaplan-Meier analysis showed that patients with tumors showing greater reduction in SUVmax had favorable progression-free survival and overall survival (p=0.0009, p=0.03). In biliary tract cancers treated with GEMOX-B, the reduction of SUVmax after therapy is a better predictor for survival than morphologic and density changes.

  6. Radiation-induced irreparable heritable changes in cells promoting their tumoral transformation

    International Nuclear Information System (INIS)

    Kuzin, A.M.; Vagabova, M.Eh.; Yurov, S.S.

    1988-01-01

    In experiments with model plant tumors (Kalanchoe-ti plasmid Agrobat. tumefaciens C-58D) it was shown that exposure of the recepient plant to low-level γ-radiation of Gy induced changes in cells that were not repaired over two months promoting tumoral transformations in them. Those changes were shown to persist in the offspring of the exposed somatic cells

  7. FDG uptake in cold and heat treated MCF-7 cells, comparison with cell viability, apoptosis, and tumor marker changes

    International Nuclear Information System (INIS)

    Zhang, C.; Sun, X.; Huang, G.; Liu, J.

    2007-01-01

    Full text: Objectives-To investigate the FDG uptake changes in cold and hyperthermia therapy and its correlation with cell viability, apoptosis and tumor marker changes. Methods: An in vitro cultured breast adenocarcinoma cell line, MCF- 7, was divided into 5 groups. Hyperthermia group: cell was treated in 43 degree centigrade 30 min. Hypothermia group: cell was treated in 0 degree centigrade 30 min. Hypo- and hyperthermia group: cell was treated in 0 degree centigrade 30 min and 43 degree centigrade 30 min. chemotherapy group: cell was treated with 21 microgram Cisplatin for 6 hours. And Control group: cell was untreated. The levels 18F-labelled FDG uptake, a 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazoliumbromide viability assay, flow cytometry assay and tumor markers (CA153, CA125) were detected at 24 hour and 48 hour. Results: The change of 18F- FDG uptake (which came out at the 24h) is early than tumor marker (which came out at the 48h) under our study conditions. In treated MCF-7 cells, the levels of 18F-labelled FDG uptake were significantly lower than control group. The levels of 18F-FDG uptake depression were well correlated with cell viability and apoptosis data. Conclusion: FDG uptake is sensitive and well correlated with cell viability and apoptosis assay, and can be used for early response monitoring in hypo- and hyperthermia therapy. (author)

  8. Tumor responsive targeted multifunctional nanosystems for cancer imaging, chemo- and siRNA therapy

    Science.gov (United States)

    Savla, Ronak

    Cancer is one of the most insidious diseases. Compromising of over 100 different types and sharing the unifying factors of uncontrolled growth and metastasis, unmet clinical needs in terms of cancer diagnosis and treatment continue to exist. It is widely accepted that most forms of cancer are treatable or even curable if detected before widespread metastasis occurs. Nearly a quarter of deaths in the United States is the result of cancer and it only trails heart disease in terms of annual mortality. Surgery, chemotherapy, and radiation therapy are the primary treatment modalities for cancer. Research in these procedures has resulted in substantial benefits for cancer patients, but there is still room for an improvement. However, a time has been reached at which it appears that the benefits from these modalities have been reached the maximum. Therefore, it is vital to develop new strategies for the diagnosis and treatment of cancer. The field of nanotechnology is concerned with structures in the nanometer size range and holds the potential to drastically impact and improve the lives of patients suffering from cancer. Not only can nanotechnology improve current methods of diagnosis and treatment, it has a possibility of introducing newer and better modalities. The overall purpose of this work is to develop novel nanotechnology-based methodologies for the diagnosis and treatment of various forms of cancers. The first aim of the project is the development of a multifunctional targeted nanosystem for the delivery of siRNA to overcome drug resistance. The second aspect is the synthesis of a quantum dot-based delivery system that releases drug in response to pH changes. The third aim is the development of a targeted, tumor environment responsive magnetic resonance nanoparticle contrast agent coupled with a nanoparticle-based treatment.

  9. Dose impact of a carbon fiber couch for stereotactic body radiation therapy of lung tumors

    International Nuclear Information System (INIS)

    Tominaga, Hirofumi; Kanetake, Nagisa; Kawasaki, Keiichi; Iwashita, Yuki; Sakata, Junichi; Okuda, Tomoko; Araki, Fujio; Shimohigashi, Yoshinobu; Tomiyama, Yuki

    2013-01-01

    The aim of this study was to measure the dose attenuation caused by a carbon fiber radiation therapy table (Imaging Couch Top; ICT, BrainLab) and to evaluate the dosimetric impact of ICT during stereotactic body radiation therapy (SBRT) in lung tumors. The dose attenuation of ICT was measured using an ionization chamber and modeled by means of a treatment planning system (TPS). SBRT was planned with and without ICT in a lung tumor phantom and ten cases of clinical lung tumors. The results were analyzed from isocenter doses and a dose-volume histogram (DVH): D 95 , D mean , V 20 , V 5 , homogeneity index (HI), and conformity index (CI). The dose attenuation of the ICT modeled with TPS agreed to within ±1% of the actually measured values. The isocenter doses, D 95 and D mean with and without ICT showed differences of 4.1-5% for posterior single field and three fields in the phantom study, and differences of 0.6-2.4% for five fields and rotation in the phantom study and six fields in ten clinical cases. The dose impact of ICT was not significant for five or more fields in SBRT. It is thus possible to reduce the dose effect of ICT by modifying the beam angle and beam weight in the treatment plan. (author)

  10. Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy.

    Science.gov (United States)

    Geng, Jie-Jie; Tang, Juan; Yang, Xiang-Min; Chen, Ruo; Zhang, Yang; Zhang, Kui; Miao, Jin-Lin; Chen, Zhi-Nan; Zhu, Ping

    2017-06-01

    CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative) and fully committed DP (double positive) cells into innate NK-like lineages. Mechanistically, CD147 deficiency results in impaired Wnt signaling and expression of BCL11b, a master transcription factor in determining T cell identity. In addition, functional blocking of CD147 by antibody phenocopies genetic deletion to enrich NK-like cells in the periphery. Furthermore, using a melanoma model and orthotopic liver cancer transplants, we showed that the augmentation of NK-like cells strongly associates with resistance against tumor growth upon CD147 suppression. Therefore, besides its original function in tumorigenesis, CD147 is also an effective surface target for immune modulation in tumor therapy. Copyright © 2017. Published by Elsevier B.V.

  11. Proton radiation therapy for retinoblastoma: Comparison of various intraocular tumor locations and beam arrangements

    International Nuclear Information System (INIS)

    Krengli, Marco; Hug, Eugen B.; Adams, Judy A.; Smith, Alfred R.; Tarbell, Nancy J.; Munzenrider, John E.

    2005-01-01

    Purpose: To study the optimization of proton beam arrangements for various intraocular tumor locations; and to correlate isodose distributions with various target and nontarget structures. Methods and materials: We considered posterior-central, nasal, and temporal tumor locations, with straight, intrarotated, or extrarotated eye positions. Doses of 46 cobalt grey equivalent (CGE) to gross tumor volume (GTV) and 40 CGE to clinical target volume (CTV) (2 CGE per fraction) were assumed. Using three-dimensional planning, we compared isodose distributions for lateral, anterolateral oblique, and anteromedial oblique beams and dose-volume histograms of CTVs, GTVs, lens, lacrimal gland, bony orbit, and soft tissues. Results: All beam arrangements fully covered GTVs and CTVs with optimal lens sparing. Only 15% of orbital bone received doses ≥20 CGE with a lateral beam, with 20-26 CGE delivered to two of three growth centers. The anterolateral oblique approach with an intrarotated eye resulted in additional reduction of bony volume and exposure of only one growth center. No appreciable dose was delivered to the contralateral eye, brain tissue, or pituitary gland. Conclusions: Proton therapy achieved homogeneous target coverage with true lens sparing. Doses to orbit structures, including bony growth centers, were minimized with different beam arrangements and eye positions. Proton therapy could reduce the risks of second malignancy and cosmetic and functional sequelae

  12. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs). Recent insights and advances

    International Nuclear Information System (INIS)

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, R.T.

    2012-01-01

    Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. (author)

  13. The development of CAR design for tumor CAR-T cell therapy.

    Science.gov (United States)

    Xu, Dandan; Jin, Guoliang; Chai, Dafei; Zhou, Xiaowan; Gu, Weiyu; Chong, Yanyun; Song, Jingyuan; Zheng, Junnian

    2018-03-02

    In recent years, the chimeric antigen receptor modified T cells (Chimeric antigen receptor T cells, CAR-T) immunotherapy has developed rapidly, which has been considered the most promising therapy. Efforts to enhance the efficacy of CAR-based anti-tumor therapy have been made, such as the improvement of structures of CAR-T cells, including the development of extracellular antigen recognition receptors, intracellular co-stimulatory molecules and the combination application of CARs and synthetic small molecules. In addition, effects on the function of the CAR-T cells that the space distance between the antigen binding domains and tumor targets and the length of the spacer domains have are also being investigated. Given the fast-moving nature of this field, it is necessary to make a summary of the development of CAR-T cells. In this review, we mainly focus on the present design strategies of CAR-T cells with the hope that they can provide insights to increase the anti-tumor efficacy and safety.

  14. Associations between pathologic tumor features and preadjuvant therapy cognitive performance in women diagnosed with breast cancer.

    Science.gov (United States)

    Koleck, Theresa A; Bender, Catherine M; Sereika, Susan M; Ryan, Christopher M; Ghotkar, Puja; Brufsky, Adam M; Jankowitz, Rachel C; McAuliffe, Priscilla F; Clark, Beth Z; Conley, Yvette P

    2017-02-01

    Intertumor heterogeneity has been proposed as a potential mechanism to account for variability in cognitive performance in women diagnosed with breast cancer. The purpose of this study was to explore associations between variation in pathologic tumor features (PTFs) and variability in preadjuvant therapy cognitive performance in postmenopausal women newly diagnosed with early-stage breast cancer. Participants (N = 329) completed a comprehensive battery of neuropsychological tests to evaluate cognitive performance after primary surgery but prior to initiation of adjuvant anastrozole±chemotherapy. PTF data were abstracted from medical records. Robust multiple linear regression models were fit to estimate associations between individual PTFs and the cognitive function composite domain scores. All models controlled for age, estimated intelligence, and levels of depressive symptoms, anxiety, fatigue, and pain. Diagnosis of a HER2-positive tumor contributed to poorer verbal (b = -0.287, P = 0.018), visual (b = -0.270, P = 0.001), and visual working (b = -0.490, P Breast Cancer Assay Recurrence Score ® .) Our results suggest that certain PTFs related to more aggressive tumor phenotypes or inferior breast cancer prognosis may be implicated in poorer preadjuvant therapy cognitive performance. Follow-up studies that include a cognitive assessment before primary surgery should be conducted to further delineate the role of intertumor heterogeneity on cognitive performance. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. Perspectives of boron-neutron capture therapy of malignant brain tumors

    Science.gov (United States)

    Kanygin, V. V.; Kichigin, A. I.; Krivoshapkin, A. L.; Taskaev, S. Yu.

    2017-09-01

    Boron neutron capture therapy (BNCT) is characterized by a selective effect directly on the cells of malignant tumors. The carried out research showed the perspective of the given kind of therapy concerning malignant tumors of the brain. However, the introduction of BNCT into clinical practice is hampered by the lack of a single protocol for the treatment of patients and the difficulty in using nuclear reactors to produce a neutron beam. This problem can be solved by using a compact accelerator as a source of neutrons, with the possibility of installation in a medical institution. Such a neutron accelerator for BNCT was developed at Budker Institute of Nuclear Physics, Novosibirsk. A neutron beam was obtained on this accelerator, which fully complies with the requirements of BNCT, as confirmed by studies on cell cultures and experiments with laboratory animals. The conducted experiments showed the relative safety of the method with the absence of negative effects on cell cultures and living organisms, and also confirmed the effectiveness of BNCT for malignant brain tumors.

  16. Targeting CD147 for T to NK Lineage Reprogramming and Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Jie-Jie Geng

    2017-06-01

    Full Text Available CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative and fully committed DP (double positive cells into innate NK-like lineages. Mechanistically, CD147 deficiency results in impaired Wnt signaling and expression of BCL11b, a master transcription factor in determining T cell identity. In addition, functional blocking of CD147 by antibody phenocopies genetic deletion to enrich NK-like cells in the periphery. Furthermore, using a melanoma model and orthotopic liver cancer transplants, we showed that the augmentation of NK-like cells strongly associates with resistance against tumor growth upon CD147 suppression. Therefore, besides its original function in tumorigenesis, CD147 is also an effective surface target for immune modulation in tumor therapy.

  17. In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy

    Science.gov (United States)

    Laufer, Jan; Johnson, Peter; Zhang, Edward; Treeby, Bradley; Cox, Ben; Pedley, Barbara; Beard, Paul

    2012-05-01

    The use of a novel all-optical photoacoustic scanner for imaging the development of tumor vasculature and its response to a therapeutic vascular disrupting agent is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor for mapping the photoacoustic waves and an image reconstruction algorithm based upon attenuation-compensated acoustic time reversal. The system was used to noninvasively image human colorectal tumor xenografts implanted subcutaneously in mice. Label-free three-dimensional in vivo images of whole tumors to depths of almost 10 mm with sub-100-micron spatial resolution were acquired in a longitudinal manner. This enabled the development of tumor-related vascular features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to be visualized over time. The system was also used to study the temporal evolution of the response of the tumor vasculature following the administration of a therapeutic vascular disrupting agent (OXi4503). This revealed the well-known destruction and recovery phases associated with this agent. These studies illustrate the broader potential of this technology as an imaging tool for the preclinical and clinical study of tumors and other pathologies characterized by changes in the vasculature.

  18. Stereotactic Ablative Radiation Therapy for Subcentimeter Lung Tumors: Clinical, Dosimetric, and Image Guidance Considerations

    International Nuclear Information System (INIS)

    Louie, Alexander V.; Senan, Suresh; Dahele, Max; Slotman, Ben J.; Verbakel, Wilko F.A.R.

    2014-01-01

    Purpose: Use of stereotactic ablative radiation therapy (SABR) for subcentimeter lung tumors is controversial. We report our outcomes for tumors with diameter ≤1 cm and their visibility on cone beam computed tomography (CBCT) scans and retrospectively evaluate the planned dose using a deterministic dose calculation algorithm (Acuros XB [AXB]). Methods and Materials: We identified subcentimeter tumors from our institutional SABR database. Tumor size was remeasured on an artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses were generated using either a pencil beam convolution or an anisotropic analytic algorithm (AAA). All AAA plans were recalculated using AXB, and differences among D95 and mean dose for internal target volume (ITV) and planning target volume (PTV) on the average intensity CT dataset, as well as for gross tumor volume (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT scans acquired during each treatment fraction were evaluated for target visibility. Progression-free and overall survival rates were calculated using the Kaplan-Meier method. Results: Thirty-five patients with 37 subcentimeter tumors were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95 ± SD values were 2.2 ± 4.4% (ITV) and 2.5 ± 4.8% (PTV) lower using AXB; whereas mean doses were 2.9 ± 4.9% (ITV) and 3.7 ± 5.1% (PTV) lower. Calculated AXB doses were significantly lower in one patient (difference in mean ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%). However, the end respiratory phase GTV received at least 95% of the prescription dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was visualized in 82 images, and its position could be inferred in other images. The 2-year local progression-free survival was 100%. Conclusions: Patients with subcentimeter lung tumors are good candidates for SABR, given the dosimetry, ability to localize

  19. Interest of synchrotron radiation for the therapy of brain tumors: methodology and preclinical applications

    International Nuclear Information System (INIS)

    Regnard, P.

    2007-12-01

    Microbeam radiation (M.R.T.) and stereotactic synchrotron radiation therapy (S.S.R.T.) are innovative techniques currently developed at the european Synchrotron radiation facility. these techniques led to promising, but rarely reproduced, results. the use of different tumoral models for each techniques limit comparisons. M.R.T. experiments on rats bearing 9L tumors 14 days after implantation displayed a double median survival time ( from 20 to 40 days) with a 200 μm spacing irradiation, while a 100 μm spacing irradiation tripled this median (67 days) but damaged normal tissue. the impact of the device dividing synchrotron beam into micro-beams, named multi sit collimator, was also demonstrated. combination of drugs with M.R.T. irradiation was tested. promising results (median survival time: 40 days and 30% of long term survivors) were obtained with an intratumoral injection of gadolinium coupled with a crossing M.R.T. irradiation at 460 Gy. Moreover, earlier M.R.T. irradiation (tumor at D10) quadrupled the median survival time (79 days) with 30% of long term survivors. A new imaging device to target the tumor before irradiation and an adapted collimator will increase the M.R.T. results. As the differences existing between tumoral models used in M.R.T. (9L models) and in S.S.R.T. (F98 models) are major, M.R.T./S.S.R.T. comparative experiments were realised on these two models. Results showed that the two techniques have the same efficacy on F98 model and that the M.R.T. is more effective on 9L model. This can help to define adapted tumor type for these techniques. (author)

  20. Differentiation between vasogenic-edema versus tumor-infiltrative area in patients with glioblastoma during bevacizumab therapy: A longitudinal MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Artzi, Moran, E-mail: artzimy@gmail.com [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Bokstein, Felix, E-mail: felixb@tlvmc.gov.il [Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Blumenthal, Deborah T., E-mail: deborahblumenthal@gmail.com [Neuro-Oncology Service, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Aizenstein, Orna, E-mail: Ornaaizenstein@gmail.com [Functional Brain Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Liberman, Gilad, E-mail: giladliberman@gmail.com [Functional Brain Center, Tel Aviv So