Studies on cross-immunity among syngeneic tumors by immunization with gamma-irradiated tumor cells

International Nuclear Information System (INIS)

Ito, Izumi

1977-01-01

In order to clarify whether cross-immunity among 3-methyl-cholanthrene (MCA)-induced sarcomas in C3H/He mice can be established or not, transplantations of syngeneic tumors were carried out in mice immunized with gamma-irradiated (13,000 rad 60 Co) tumor cells and in those immunized with living tumor cells thereafter. The following results were obtained. By using immunizing procedure with only gamma-irradiated tumor cells, a pair of tumors originating from one and the same mouse showed cross-resistance to each other. However, no such evidence was seen among tumors originating from different mice. Cross-immunity among syngeneic tumors originating from different mice could be clearly observed, when immunizing procedure using living tumor cells was added after the treatment with gamma-irradiated tumor cells. It was considered that common antigenicity among MCA-induced sarcoma cells was decreased by gamma-irradiation and that individual differences of tumor antigenecity were shown distinctly under such conditions. (auth.)

Irradiation effects on the tumor and adjacent tissues of brain tumor-bearing mice

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Tsunemoto, Hiroshi; Koike, Sachiko; Furukawa, Shigeo.

1979-01-01

C 3 H mice aged 56 - 70 days, weighing 27 - 37 g were used throughout this experiment. A transplantable fibrosarcoma arising spontaneously from C 3 H mice was used. For experiment, 10 4 tumor cells suspended in 0.025 ml of saline solution were injected into the cerebral hemisphere by a 26 gauge needle with a micrometer syringe under nembutal anesthesia. Whole brain irradiation was performed at 7 days after injection of the tumor cells and the radiation doses were 2,000 and 20,000 rads, respectively. The feature of x-rays were 200 kVp, 20 mA, 0.5 mm Cu + 0.5 mm Al filtration and TSD 20 cm. The dose-rate was 340 - 360 R/min. The articles of this study were as follows: a) Determination of LD 50 values for the mice, tumor-bearing in the brain or non-tumor-bearing; and b) Observation of clinical features and gross autopsy findings of the mice following irradiation. The LD 50 values for 2,000 rad irradiation in the tumor-bearing or non-tumor-bearing mice were 10.9 and 11.4 days, respectively. LD 50 values of 3.7 days and 4.3 days were the results for the tumor-bearing and non-tumor-bearing mice irradiated by 20,000 rad, respectively. On the other hand, the LD 50 value for the control group, i.e. non-irradiated mice, was 6.7 days. At postmortem examinations, gastrointestinal bleeding was observed frequently in mice bearing tumor in the brain. Whole brain irradiation is effective to prolong the life of tumor-bearing mice. However, in some instances, deaths have occurred earlier in tumor-bearing mice compared to the control group. (author)

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

International Nuclear Information System (INIS)

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

1983-01-01

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

Localization of the experimental tumor regrowth after irradiation

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Yamaura, H; Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis and Cancer

1978-08-01

The process of the structural changes in the irradiated AH109A tumor and its regrowth was studied, using histologic and transparent-chamber techniques. The tumor tissue was divided into four successive layers, according to vascular morphology and measures. The vascularity was the greatest in the outermost region and decreased towards the inner part of the tumor until necrosis. The tumor was irradiated with various doses of x and gamma-rays. The inside hypoxic region was destroyed completely after 3,000 rad and regrowths started from the outermost area of the tumor where oxygen enhancing effect to irradiation was supposed to be the greatest.

WE-EF-BRA-11: Precision Partial-Tumor Irradiation of Dorsal Rodent Mammary Tumors

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Malcolm, J [Duke Medical Physics Graduate Program, Durham, NC (United States); Boss, K [Department of Comparative Biomedical Sciences, North Carolina State University (United States); Dewhirst, M [Dpt of Radiation and Cancer Biology, Duke University, Durham, North Carolina (United States); Oldham, M [Dpt of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

2015-06-15

Purpose: To introduce a pre-clinical treatment technique on a micro-irradiator to treat specific volumes of dorsal mammary tumors in BALB/c mice while sparing lungs and spine. This technique facilitates pre-clinical investigation of tumor response to sub-optimal radiation treatments in which a portion of the tumor is unirradiated, known as a “marginal miss”. In-vitro data suggests that partial tumor radiations trigger a more aggressive phenotype in non-irradiated, regional tumor cells via bystander effects. As the lung tissue is spared, the impact of marginal miss on the development of pulmonary metastasis may be assessed. Methods: End to end test was performed on three BALB/c mice as proof of concept for larger studies. 1Gy was delivered on the micro-irradiator employing previously unexplored lateral parallel-opposed diamond and/or triangle-shaped beams. The margins of the treatment beam were defined using a combination of tumor palpation, barium fiducial markers, and real-time fluoroscopic images. The dose distribution was independently verified with kilovoltage beam Monte Carlo dose calculations with 7% statistical uncertainty and double exposure images. As a final step, the technique was used in a larger pre-clinical study (15Gy, 36 BALB/c mice) and lung metastasis in response to tumor irradiation of 100%, 50% and 0% was quantified. Results: For the Monte-Carlo dose calculations, the dose volume histograms established a maximum dose within the un-irradiated and radiated portions of the mammary tumor of 0.3Gy and 1.5Gy respectively, with a sharp gradient at the boundary. 100% of the lung volume received less than 0.5Gy. This technique proved suitable for a pre-clinical marginal miss study with 50% more lung metastases in partially-radiated mouse models compared to completely. Conclusion: We have developed a novel treatment technique for partial or full irradiation of dorsal mammary tumors incorporating lung sparing.The technique will be useful for exploring

Lysosomal enzyme activation in irradiated mammary tumors

International Nuclear Information System (INIS)

Clarke, C.; Wills, E.D.

1976-01-01

Lysosomal enzyme activity of C3H mouse mammary tumors was measured quantitatively by a histochemical method. Following whole-body doses of 3600 rad or less no changes were observed in the lysosomal enzyme activity for 12 hr after the irradiation, but very large increases in acid phosphatase and β-naphthylamidase activity were, however, observed 24 hr after irradiation. Significant increases in enzyme activity were detected 72 hr after a dose of 300 rad and the increases of enzyme activity were dose dependent over the range 300 to 900 rad. Testosterone (80 mg/kg) injected into mice 2 hr before irradiation (850 rad) caused a significant increase of lysosomal enzyme activity over and above that of the same dose of irradiation alone. If the tumor-bearing mice were given 95 percent oxygen/5 percent carbon dioxide to breathe for 8 min before irradiation the effect of 850 rad on lysosomal acid phosphatase was increased to 160 percent/that of the irradiation given alone. Activitation of lysosomal enzymes in mammary tumors is an important primary or secondary consequence of radiation

Human autologous in vitro models of glioma immunogene therapy using B7-2, GM-CSF, and IL12

International Nuclear Information System (INIS)

Parney, I.F.; Farr-Jones, M.A.; Kane, K.; Chang, L.-J.; Petruk, K.C.

2002-01-01

Cancer immunogene therapy is based on vaccination with radiated, autologous tumor cells transduced with immunostimulatory genes. To help determine an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12). A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti-tumor cytotoxicity was determined by chromium-51 ( 51 Cr) release assay. Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2,GM-CSF,and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12) transduced cells. PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of turnor subclones with limited antigenic spectra during retrovirus-mediated gene transfer. (author)

Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells.

Science.gov (United States)

Burkhardt, Ute E; Hainz, Ursula; Stevenson, Kristen; Goldstein, Natalie R; Pasek, Mildred; Naito, Masayasu; Wu, Di; Ho, Vincent T; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L; Brusic, Ana; McDonough, Sean M; Zeng, Wanyong; Perrin, Ann; Brown, Jennifer R; Canning, Christine M; Koreth, John; Cutler, Corey; Armand, Philippe; Neuberg, Donna; Lee, Jeng-Shin; Antin, Joseph H; Mulligan, Richard C; Sasada, Tetsuro; Ritz, Jerome; Soiffer, Robert J; Dranoff, Glenn; Alyea, Edwin P; Wu, Catherine J

2013-09-01

Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-γ, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. Clinicaltrials.gov NCT00442130. NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.

Inhibition of IL-17A suppresses enhanced-tumor growth in low dose pre-irradiated tumor beds.

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Eun-Jung Lee

Full Text Available Ionizing radiation induces modification of the tumor microenvironment such as tumor surrounding region, which is relevant to treatment outcome after radiotherapy. In this study, the effects of pre-irradiated tumor beds on the growth of subsequently implanted tumors were investigated as well as underlying mechanism. The experimental model was set up by irradiating the right thighs of C3H/HeN mice with 5 Gy, followed by the implantation of HCa-I and MIH-2. Both implanted tumors in the pre-irradiated bed showed accelerated-growth compared to the control. Tumor-infiltrated lymphocyte (TIL levels were increased, as well as pro-tumor factors such as IL-6 and transforming growth factor-beta1 (TGF-β1 in the pre-irradiated group. In particular, the role of pro-tumor cytokine interleukin-17A (IL-17A was investigated as a possible target mechanism because IL-6 and TGF-β are key factors in Th17 cells differentiation from naïve T cells. IL-17A expression was increased not only in tumors, but also in CD4+ T cells isolated from the tumor draining lymph nodes. The effect of IL-17A on tumor growth was confirmed by treating tumors with IL-17A antibody, which abolished the acceleration of tumor growth. These results indicate that the upregulation of IL-17A seems to be a key factor for enhancing tumor growth in pre-irradiated tumor beds.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.

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Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G; Scholler, John; Levine, Bruce L; Albelda, Steven M; June, Carl H

2010-11-15

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week after electroporation. Multiple injections of RNA CAR-electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(-/-) mice. Dramatic tumor reduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been growing in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes showing that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Copyright © 2010 AACR.

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

Science.gov (United States)

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

2018-01-01

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

Re-irradiation for abdominal tumor. Preliminary results

International Nuclear Information System (INIS)

Narisada, Hiroyuki; Imada, Hajime; Tomoda, Yoshinori

2012-01-01

The purpose of this study was to assess the efficacy of loco-regional radiotherapy for recurrent abdominal tumor treated with re-irradiation. Re-irradiated areas of 16 patients were eight of pelvic space, five of retroperitonium and three of liver or porta hepatica. Eligibility criteria of re-irradiation were success of initial irradiation, no other effective treatment except re-irradiation, constancy of bowel gas at hunger status and respiratory movement, visceral dosage reduction at re-irradiation. Total dose of initial, second course of radiation were 51.3±10.8 Gy, 50.6±14.2 Gy, respectively. Interval of initial and second course of radiation were 16.6±10.2 months. Local control after second course of radiation was four cases of complete response, five of partial response and seven of stable disease. Median survival periods were 55 months after initial treatment and 28 months after second course of radiation. In two cases of pelvic reirradiation, skin to pelvic space fistula was occurred. Re-irradiation for abdominal tumor may become useful salvage treatment. (author)

Soybean diet breast tumor incidence in irradiated rats

International Nuclear Information System (INIS)

Troll, W.; Wiesner, R.

1980-01-01

The relationship between feeding a diet rich in protease inhibitors and the reduction of mammary cancer induced by x-irradiation in Sprague-Dawley rats was examined. Of a total of 145 irradiated animals, 44% of the 45 rats fed a raw soybean diet containing a high concentration of protease inhibitor developed mammary tumors as compared to 74% of 50 rats fed a casein diet containing no protease inhibitor. Animals fed Purina rat chow which contained low levels of protease inhibitor exhibited a 70% mammary tumor incidence. No spontaneous neoplasms were found in any of the non-irradiated animals on the raw soybean diet whereas about 10% of the animals on the protease-free diet developed tumors. Thus, soybeans which are rich in protease inhibitors reduced the induction of mammary cancer in x-irradiated rats. This suggested that diets rich in protease inhibitors may contribute to reducing cancer incidence in man. (author)

Effects of carbogen plus fractionated irradiation on KHT tumor oxygenation

International Nuclear Information System (INIS)

Fenton, Bruce M.

1997-01-01

Background and purpose: Numerous studies have demonstrated improvements in the oxygenation of tumor cells following both irradiation and carbogen breathing. The current studies were initiated to measure the combined effects of carbogen inhalation plus single and multi-dose irradiation on tumor oxygen availability, to better define the underlying physiological relationships. Materials and methods: Using KHT murine sarcomas, radiation was delivered to the tumor-bearing legs of non-anesthetized mice. Tumors were quick-frozen prior to or following single or multifraction irradiation and carbogen breathing, and intravascular HbO 2 saturation profiles were determined cryospectrophotometrically. Results: HbO 2 levels for blood vessels located near the tumor surface initially decreased following 10 Gy irradiation, then increased and remained elevated. Interior HbO 2 levels remained unchanged. Following 2.5 Gy, HbO 2 changes were minimal. At 24 h following 10 Gy, HbO 2 levels were significantly increased compared to non-irradiated controls, and carbogen breathing produced no additional benefit. At 24 h following five fractions of 2 Gy, HbO 2 levels throughout the tumor volume were significantly higher in carbogen breathing animals than in air breathing controls. Conclusions: Although peripheral blood vessels demonstrated substantial improvements in oxygenation following irradiation, oxygen availability nearer the tumor center remained at very low levels. The utility of carbogen in enhancing tumor oxygen availability was maintained following five clinically relevant fractions. At higher doses, radiation-induced enhancements in HbO 2 levels overshadowed the carbogen effect. For either air or carbogen breathing, a decrease in the percentage of vessels with very low oxygen content did not appear to be a major factor in the reoxygenation of the KHT tumor

Radiation as an inducer of in-situ autologous vaccine in the treatment of solid tumors

International Nuclear Information System (INIS)

Ahmed, Mansoor M.

2013-01-01

Radiation therapy (RT) is conventionally used for local tumor control. Although local control of the primary tumor can prevent the development of subsequent systemic metastases, tumor irradiation is not effective in controlling pre-existing systemic disease. The concept of radiation-enhanced antigen presentation and immunomodulation allows the harnessing of tumor cell death induced by radiation as a potential source of tumor antigens for immunotherapy. Immunomodulation using RT is a novel strategy of in situ tumor vaccination where primary tumor irradiation can contribute to the control of pre-existing systemic metastatic disease. The absence of systemic immunosuppression (often associated with chemotherapy) and the generally lower toxicity makes radiation a desirable adjuvant regimen for immunotherapy and tumor vaccination strategies. Increased understanding of tumor immunology and the biology of radiation-mediated immune modulation should enhance the efficacy of combining these therapeutic modalities. Here we aim to provide an overview of the biology of radiation-induced immune modulation. (author)

Stereotactic irradiation for metastatic brain tumor

International Nuclear Information System (INIS)

Nomura, Ryutaro

2017-01-01

First, this paper reviewed the latest findings of stereotactic irradiation (STI) for metastatic brain tumors. Then, it described the results of randomized controlled trials for single or a few (2-4) metastasis in the following comparison tests: (1) comparison between whole brain radiotherapy (WBRT) alone group and (WBRT + STI) group, (2) comparison between STI alone group and (STI + WBRT) group, (3) comparison between STI alone group and (tumorectomy + WBRT) group, (4) comparison between (STI + WBRT) group and (tumorectomy + WBRT) group, and (5) between (tumorectomy + WBRT) group and (tumorectomy + STI) group. Among these, STI alone without WBRT has obtained a certain consensus. Against multiple metastatic brain tumors of 5 or more, when considering cognitive impairment and QOL loss by adding WBRT, it is general consensus that STI alone may be sufficient. At the authors' institution, cyber knife (CK) was introduced in 2008 and nearly 300 stereotactic radiotherapy for metastatic brain tumors have been performed annually. By adopting a robot arm and development of a lesion tracking system, the positional correction against the deviation of the bone margin of the skull is guaranteed in real time to ensure accuracy during irradiation, and hypofractionated stereotactic irradiation becomes easier. (A.O.)

Preoperative intraluminal irradiation of the extrahepatic bile duct tumor

International Nuclear Information System (INIS)

Kamada, Tadashi; Tsujii, Hirohiko; Arimoto, Takuro; Irie, Goro.

1991-01-01

From 1984 through 1986, six patients with extrahepatic bile duct tumor were treated preoperatively with intraluminal irradiation of the bile duct. There were no unresectable cases and pathological examination of the surgical specimens showed moderate to remarkable tumor regression in all cases. Postoperative biliary tract hemorrhage occurred in 2 of 3 patients who received 60 Gy at a point 7.5 mm from the center of the source. With accurate preoperative diagnosis of the tumor extent and careful setting of the target area of intraluminal irradiation, improved local tumor control of extrahepatic bile duct tumor can be expected with this method. (author)

An Effective Approach for Immunotherapy Using Irradiated Tumor Cells

International Nuclear Information System (INIS)

Mostafa, D.M.B.

2011-01-01

This study has been aimed to investigate the effect of injection of Irradiated Ehrlich tumor cells alone or concurrent with immunomodulator in mice before and after challenge with viable Ehrlich tumor cells for enhancement of immune system. This study includes the estimation of survival, tumor size, lymphocyte count, LDH, MTT, granzyme B, and DNA fragmentation. In order to fulfill the target of this study, a total of 120 female swiss albino mice were used. They were divided into two classes vaccinated (injection of vaccine before challenge) and therapeutic class (injection of vaccine after challenge). Each class was divided into four groups, group (1) mice injected with viable Ehrlich tumor cells (G1), group (2) mice injected with irradiated tumor cells (G2), group (3) mice injected with immunomodulator (G3), and group (4) mice injected with irradiated tumor cells + immunomodulator (G4). Results obtained from this study demonstrated that, the lymphocyte count and granzyme B activity were increased in both the vaccinated and therapeutic classes compared with control group. LDH activity was decreased in all groups of vaccinated class and also in G2 and G4 groups of therapeutic class compared with control group. There was a significant increase in percent apoptosis of tumor cells cultured with spleenocytes of the groups of vaccinated class as compared with control group. Cellular DNA from Ehrlich tumor cell line cultured with spleenocytes of immunized groups was fragmented into discrete bands of approximate multiples of 200 bp. Revealing significant apoptosis in tumor cells due to vaccination. It is concluded that, vaccination with irradiated tumor cells is an effective approach in stimulation of immune system against viable tumor cells.

The influence of autologous tumor fibroblasts on the radiosensitivity of squamous cell carcinoma megacolonies

International Nuclear Information System (INIS)

Kummermehr, Johann; Malinen, Eirik; Freykowski, Sabine; Sund, Malte; Trott, Klaus-Ruediger

2001-01-01

Purpose: To study the influence of tumor fibroblasts on radiosensitivity and stem cell fraction of tumor cells in squamous cell carcinoma megacolonies by determining colony cure and clonogen survival. Methods and Materials: Murine squamous cell carcinoma cells (AT478c) grown as flat but multilayered megacolonies were co-cultured with pre-irradiated tumor fibroblasts derived from the same carcinoma, and irradiated with 1, 2, 4, or 8 fractions. Recurrent clones and their growth pattern in situ were recorded. From megacolony cure data and clonogen survival data, the clonogen number and the parameters of cellular radiosensitivity were calculated. Results: The curability of the co-cultured megacolonies, as determined by TCD50 values, was significantly increased compared to the megacolonies without fibroblasts (p<0.01). Both the megacolony cure and clonogen survival data suggested a decrease of the clonogen fraction in the co-cultured megacolonies. Conclusion: The presence of tumor fibroblasts increases megacolony radiosensitivity. This is due to a decrease in the fraction of clonogens in the tumor megacolony, apparently caused by a downregulation of the stem cell fraction of the tumor cells

The anti-tumor effect of ACNU and x-irradiation on mouse glioma

International Nuclear Information System (INIS)

Nakagawa, Hidemitsu; Hori, Masaharu; Hasegawa, Hiroshi; Mogami, Heitaro; Hayakawa, Toru.

1979-01-01

Anti-tumor activities of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and x-irradiation on methylcholanthrene induced glioma in C 57 BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and x-irradiation in M phase. As to the combined therapy of ACNU and x-irradiation, the anti-tumor effect was most remarkable when the cells were treated by x-irradiation in the G 2 , M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and x-irradiation on the cells in G 1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and x-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local x-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or x-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of x-ray was remarkably effective. Evidence obtained indicated that the combination therapy of ACNU and x-irradiation have synergistic anti-tumor effect on experimental mouse glioma. (author)

Generation of autologous tumor-specific T cells for adoptive transfer based on vaccination, in vitro restimulation and CD3/CD28 dynabead-induced T cell expansion

DEFF Research Database (Denmark)

Brimnes, Marie Klinge; Gang, Anne Ortved; Donia, Marco

2012-01-01

Adoptive cell transfer (ACT) of in vitro expanded autologous tumor-infiltrating lymphocytes (TIL) has been shown to exert therapeutic efficacy in melanoma patients. We aimed to develop an ACT protocol based on tumor-specific T cells isolated from peripheral blood and in vitro expanded by Dynabeads...

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

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Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

2017-01-01

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

Irradiation promotes Akt-targeting therapeutic gene delivery to the tumor vasculature

International Nuclear Information System (INIS)

Sonveaux, Pierre; Frerart, Francoise; Bouzin, Caroline; Brouet, Agnes; Wever, Julie de; Jordan, Benedicte F.; Gallez, Bernard; Feron, Olivier

2007-01-01

Purpose: To determine whether radiation-induced increases in nitric oxide (NO) production can influence tumor blood flow and improve delivery of Akt-targeting therapeutic DNA lipocomplexes to the tumor. Methods and Materials: The contribution of NO to the endothelial response to radiation was identified using NO synthase (NOS) inhibitors and endothelial NOS (eNOS)-deficient mice. Reporter-encoding plasmids complexed with cationic lipids were used to document the tumor vascular specificity and the efficacy of in vivo lipofection after irradiation. A dominant-negative Akt gene construct was used to evaluate the facilitating effects of radiotherapy on the therapeutic transgene delivery. Results: The abundance of eNOS protein was increased in both irradiated tumor microvessels and endothelial cells, leading to a stimulation of NO release and an associated increase in tumor blood flow. Transgene expression was subsequently improved in the irradiated vs. nonirradiated tumor vasculature. This effect was not apparent in eNOS-deficient mice and could not be reproduced in irradiated cultured endothelial cells. Finally, we combined low-dose radiotherapy with a dominant-negative Akt gene construct and documented synergistic antitumor effects. Conclusions: This study offers a new rationale to combine radiotherapy with gene therapy, by directly exploiting the stimulatory effects of radiation on NO production by tumor endothelial cells. The preferential expression of the transgene in the tumor microvasculature underscores the potential of such an adjuvant strategy to limit the angiogenic response of irradiated tumors

Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

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Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

2016-01-01

Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

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Sejal Desai

Full Text Available Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2 and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper

Long-term follow-up of endocrine function among young children with newly diagnosed malignant central nervous system tumors treated with irradiation-avoiding regimens.

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Cochrane, Anne M; Cheung, Clement; Rangan, Kasey; Freyer, David; Nahata, Leena; Dhall, Girish; Finlay, Jonathan L

2017-11-01

The adverse effects of irradiation on endocrine function among patients with pediatric brain tumor are well documented. Intensive induction chemotherapy followed by marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) without central nervous system (CNS) irradiation has demonstrated efficacy in a proportion of very young children with some malignant CNS tumors. This study assessed the long-term endocrine function of young children following chemotherapy-only treatment regimens. A retrospective chart review was performed on 99 patients under 6 years of age with malignant brain tumors newly diagnosed between May 1991 and October 2010 treated with irradiation-avoiding strategies. Thirty patients survived post-AuHCR without cranial irradiation for a mean of 8.1 years (range 3.0-22.25 years). The patient cohort included 18 males and 12 females (mean age at AuHCR of 2.5 years, range 0.8-5.1 years). All 30 surviving patients had documented normal age-related thyroid function, insulin-like growth factor binding protein 3 (IGF-BP3), prolactin, testosterone, and estradiol levels. Insulin-like growth factor 1 age-related levels were abnormal in one child with normal height. Ninety-seven percent of patients had normal cortisol levels, while follicle-stimulating hormone and LH levels among females were normal in 83% and 92%, respectively, and in 100% of males. Growth charts demonstrated age-associated growth within 2 standard deviations of the mean in 67% of patients. Of 10 patients (33%) with short stature, 6 had proportional diminutions in both height and weight. These findings demonstrate that the use of relatively brief, intensive chemotherapy regimens including marrow-ablative chemotherapy with AuHCR results in fewer endocrine sequelae than treatment schemes utilizing CNS irradiation. © 2017 Wiley Periodicals, Inc.

Irradiation of meningioma: a prototype circumscribed tumor for planning high-dose irradiation of the brain

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Friedman, M.

1977-01-01

The purpose of this report is to provide specific data concerning the radiation dose required to destroy meningioma, and to demonstrate that radiation doses much greater than the alleged tolerance dose, can be administered to the brain in some patients. Most meninglomas are not responsive to irradiation, but, some surgically incurable lesions benefit from irradiation with radically high doses to small volumes of tissue. The arrest of 7 of 12 consecutive meningiomas in adults for periods of 2 to 17 years following maximum tumor doses up to 8800 R in 40 days is reported in this paper. All patients, when irradiated, had active tumor in the form of inoperable primary tumor, recurrence, or known postoperative residual tumor. Three of the successful results were achieved with orthovoltage radiation. The incidence of brain damage may be acceptable to the patient when it is related to arrest of tumor growth but he must be forewarned of possible brain damage. The factors influencing the radioresponsiveness of meningioma are: the required tumor lethal dose, histology and vascularity of the tumor, anatomical site in the brain, treatment technique for each tumor site, small size of the treated volume, growth rate of the tumor, displacement of normal brain tissue by tumor, inherent individual variations of tumor and normal tissues, quality of the radiation, and tolerance of normal brain tissues. The role of these factors is discussed in the light of modern radiobiological concepts

Tumor necrosis factor alpha production in irradiated cells in vitro

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Koeteles, G.J.; Bognar, G.; Kubasova, T.

1994-01-01

Normal and tumor cell lines were used to investigate tumor necrosis factor (TNFα) production and its radiation sensitivity. The cells were irradiated with gamma rays using different doses from 0.25 Gy up to 5 Gy. The number of plated cells, changes of proliferation and TNFα production were determined during the following four post-irradiation days. For TNFα quantity measurement immuno-radiometric assay (IRMA) and enzyme amplified sensitivity assay (EASIA) was used. The results suggest that though gamma irradiation decreased cell proliferation in a dose dependent manner, the quantity produced in the post-irradiation period increased considerably in each irradiated sample. (N.T.) 3 refs.; 2 figs.; 1 tab

Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

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Benencia Fabian

2008-04-01

Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

Radiosensitizing effect of nitric oxide in tumor cells and experimental tumors irradiated with gamma rays and proton beams

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Policastro, Lucia L.; Duran, Hebe; Molinari, Beatriz L.; Somacal, Hector R.; Valda, Alejandro A.

2003-01-01

Nitric oxide (NO) has been reported to be a radiosensitizer of mammalian cells under hypoxic conditions. In a previous study, we demonstrated an enhancement in radiation response induced by NO in mouse tumor cells under aerobic conditions, with an increasing effect as a function of malignancy. The aim of the present study was to evaluate the effect of NO in tumor cells and in experimental tumors irradiated with γ rays and proton beams. Irradiations were performed with a 137 Cs γ source and with proton beams generated by the TANDAR accelerator. Tumor cells were treated with the NO donor DETA-NO and the sensitizer enhancement ratio (SER) was calculated using the α parameter of the survival curve fitted to the linear-quadratic model. Tumor cells irradiated with protons were radio sensitized by DETA-NO only in the more malignant cells irradiated with low LET protons (2.69±0.08 keV/μm). For higher LET protons there were no radiosensitizing effect. For human tumor cells pre-treated with DETA-NO and irradiated with γ rays, a significantly greater effect was demonstrated in the malignant cells (MCF-7) as compared with the near normal cells (HBL-100). Moreover, a significant decrease in tumor growth was demonstrated in mice pre-treated with the NO donor spermine and irradiated with γ rays and low LET protons as compared with mice irradiated without pre-treatment with the NO donor. In conclusion, we demonstrated a differential effect of NO as a radiosensitizer of malignant cells, both with γ rays and low LET protons. This selectivity, coupled to the in vivo inhibition of tumor growth, is of great interest for the potential use of NO releasing agents in radiotherapy. (author)

Effects of IL-6 on proliferation and apoptosis of tumor cells multi-irradiated for tumor-bearing mice

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Liu Yongbiao; Yao Side

2004-01-01

A study was carried out on effects of IL-6 on the proliferation and apoptosis of tumor cells and the expression of apoptosis relevant genes (p53, bcl-2) in tumor cells for three kinds of fractional total-body-irradiated tumor-bearing mice. The apoptotic index, proliferative index, S phase fraction of S 180 sarcoma, H 22 hepatocarcinoma and Lewis lung cancer cells were measured by flowcytometry (FCM) after total-body-irradiation and irradiation plus IL-6. The protein expression level of p53, bcl-2 in three kinds of tumors was also determined by the immunohisto-chemical method (UltraSensitive S-P). The results showed that the S phase fraction and proliferation index in Lewis lung cancer cells were lower in the irradiated plus IL-6 group than in the control, while apoptotic index was higher (P 180 sarcoma cells were opposite (P 22 hepatocarcinoma. These results revealed that IL-6 promoted the apoptosis of irradiated Lewis lung cancer cells (P 180 sarcoma (P 22 hepatocarcinoma (P>0.05). In Lewis lung cancer the expression level of p53 was lower in the IL-6 group and higher in S 180 sarcoma (P 22 hepatocarcinoma as compared with the control (P>0.05). It is considered that tumor cell's proportion in the cellular cycle is changed by IL-6 and the effects of IL-6 on the expression of p53, bcl-2 in different three kinds of tumors are different. IL-6 has radio-sensitive effects on some tumors and opposite effects on other tumors, it may be related to the expression of p53 and bcl-2 in tumor cells. (authors)

Histopathological studies on the irradiated brain tumors

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Narita, Tadao

1980-01-01

Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy. (J.P.N.)

Histopathological studies on the irradiated brain tumors

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Narita, T [Gunma Univ., Maebashi (Japan).School of Medicine

1980-01-01

Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy.

Reduction of irradiated tumor cells viability under effect of hyperglycemia

International Nuclear Information System (INIS)

Meshcherikova, V.V.; Voloshina, E.A.

1983-01-01

On Ehrlich carcinoma cells adapted to growth in vivo and in vitro, cellular mechanisms of short-term hyperglycemia effect have been studied. It has been found that SH by itself leads to the loss of viability of a part of cells of ELD solid tumors manifesting during the first 24 hours upon irradiation according to the interphase death type. Tumor cell radiation injuries arising under the effect of irradiation, usually non realized up to the first division, under SH conditions potentiate its injury effect. The phenomena observed explain partially selective injury of tumoral cells in the course of irradiation under SH conditions which testifies to the prospects of its use in clinics

Experimental studies on the effect of perfluorochemicals in tumor irradiation

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Shinoda, Jun; Iwai, Tomohiko; Hattori, Tatsuaki; Kondo, Hiroaki; Sakai, Noboru; Yamada, Hiroshi

1984-01-01

The effects of radiation therapy with Fluosol-DA on rat mammary tumors were studied. The tissue oxygen tension values of tumors in breathing mixed gas (5% carbon dioxide and 95% oxygen) with Fluosol-DA (25 ml/kg, i.v.) were significantly higher than those in room air without Fluosol-DA. The rats were divided into three groups: Group I received Fluosol-DA but no irradiation, Group II was treated with 1000 rads of irradiation using 60 Co without Fluosol-DA in room air and Group III received the same irradiation and Fluosol-DA in breathig mixed gas. In the latter group we observed a prolongation of the survival time and suppression of the tumor growth. (author)

Effect of irradiation on microviscosity of the cellular nuclear membrane of tumor and liver of tumor-carriers

International Nuclear Information System (INIS)

Mal'tseva, E.L.; Goloshchapov, A.N.; Pal'mina, N.P.; Burlakova, E.B.

1982-01-01

Changes of microviscosity of the cellular nuclear membrane of tumor and liver of tumor-carriers with developing Ehrlich ascites tumor (EAT) at various terms after lethal irradiation (650 R) were studied by spin probe method. Two iminoxyl radicals localized mainly in lipid bilayer and near probein layers of membrane lipids were used. The character and the degree of microviscosity changes in different zones of nuclear membranes point to different responses towards effect of radiation of cells of tumor-carrier organ and tumor both in viscosity properties, and in change of lipid-protein relations. The significant contribution of near protein lipid layers into general change of nuclear membrane microviscosity is marked. Microviscosity of nuclear membrane causes different responses of cellular nuclear membranes of liver of tumor-carriers and healthy animals as well as considerable (3 times) dilution of nuclear membrane of EAT cells after irradiation. It is shown that temperature dependence of times of rotatory correlation of both probes is more expressed in EAT cells of irradiated tumor-carriers, than in liver

The effect of low-dose total body irradiation on tumor control

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Sakamoto, Kiyohiko; Miyamoto, Miyako; Watabe, Nobuyuki.

1987-01-01

Total body irradiation (TBI) is considered to bring about an immunosuppressive effect on an organism, on the basis of data obtained from sublethal doses of TBI. However, there are no data on how low-dose TBI affects an organism. Over the last five years, we have been studying the effects of low-dose TBI on normal or tumor-bearing mice and the immunological background of these effects. In experimental studies, an increase in the TD50 value (the number of cells required for a tumor incidence of 50 %) in mice exposed to 10 rad was recognized and showed a remarkable increase at 6 hours to 15 hours after irradiation. TBI of 10 rad also showed an enhancement effect on tumor cell killing when given 12 hours before local tumor irradiation. In order to clarify the mechanism of this kind of effect, some immunological studies were performed using several immunological procedures, and the results suggested that 10 rad of TBI caused increasing tumor immunity in irradiated mice. Clinical trials in some patients with advanced tumors are now being undertaken on the basis of these experimental data, and the effect of TBI on tumor control appears promising, although it is too early to draw conclusions. (author)

Associations between tumor types in irradiated BALB/c female mice

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Storer, J.B.

1982-01-01

Associations between pairs of 12 different tumor types were estimated for a population of over 3800 irradiated BALB/c female mice. The associations were adjusted for age and radiation dose. Of the 66 pairs of tumor types, 21 showed significant positive or negative associations. Of these, 8 were considered to be spurious, principally because one or both of the tumors was rapidly lethal, leading to an apparent negative association. Six of the remaining 13 significant associations involed tumors of endocrine organs or tumors known to be endocrine related. Six others involved associations between lung, vascular tissue, or reticular tissue tumors, and tumors of endocrine organs. The remaining and highly negative association was between reticulum cell sarcomas and other lymphomas and leukemias. It was concluded that in irradiated female mice of this strain, at least, tumors are not independent and that alterations in host factors (principally endocrine) lead to animals developing both tumors (positive associations) or to one tumor but not the other (negative associations)

New trends in increase of efficacy of preoperative irradiation of malignant tumors

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Berdov, B A; Dunchik, V N; Firsova, P P; Sidorchenkov, V O [Akademiya Meditsinskikh Nauk SSSR, Obninsk. Nauchno-Issledovatel' skij Inst. Meditsinskoj Radiologii

1982-09-01

It was shown the use of preoperative irradiation as a means altering the biologic nature of the tumor before the operation. The main attention is paid to development of methods for preoperative irradiation of malignant tumors, i.e. macrofractionated long-distance irradiation, intracavitary, combined irradiation, as well as to study of the effect of synchronization of tumor cells with 5-fluorouracil, of local heating of the tumor, and of electron-acceptor compounds application in the preoperative period. The results of combined treatment of 1007 patients with cancer of various localization: 121 patients with laryngeal carcinoma, 397 with mammary carcinoma, 100 with pulmonary carcinoma, 258 with gastric carcinoma, 131 with rectal carcinoma, and 114 with carcinoma of the urinary bladder were analyzed.

New trends in increase of efficacy of preoperative irradiation of malignant tumors

International Nuclear Information System (INIS)

Berdov, B.A.; Dunchik, V.N.; Firsova, P.P.; Sidorchenkov, V.O.

1982-01-01

It was shown the use of preoperative irradiation as a means altering the biologic nature of the tumor before the operation. The main attention is paid to development of methods for preoperative irradiation of malignant tumors, i. e. macrofractionated long-distance irradiation, intracavitary, combined irradiation, as well as to study of the effect of synchronization of tumor cells with 5-fluorouracil, of local heating of the tumor, and of electron-acceptor compounds application in the preoperative period. The results of combined treatment of 1007 patients with cancer of various localization: 121 patients with laryngeal carcinoma, 397 with mammary carcinoma, 100 with pulmonary carcinoma, 258 with gastric carcinoma, 131 with rectal carcinoma, and 114 with carcinoma of the urinary bladder were analyzed

Enhanced responses to tumor immunization following total body irradiation are time-dependent.

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Adi Diab

Full Text Available The development of successful cancer vaccines is contingent on the ability to induce effective and persistent anti-tumor immunity against self-antigens that do not typically elicit immune responses. In this study, we examine the effects of a non-myeloablative dose of total body irradiation on the ability of tumor-naïve mice to respond to DNA vaccines against melanoma. We demonstrate that irradiation followed by lymphocyte infusion results in a dramatic increase in responsiveness to tumor vaccination, with augmentation of T cell responses to tumor antigens and tumor eradication. In irradiated mice, infused CD8(+ T cells expand in an environment that is relatively depleted in regulatory T cells, and this correlates with improved CD8(+ T cell functionality. We also observe an increase in the frequency of dendritic cells displaying an activated phenotype within lymphoid organs in the first 24 hours after irradiation. Intriguingly, both the relative decrease in regulatory T cells and increase in activated dendritic cells correspond with a brief window of augmented responsiveness to immunization. After this 24 hour window, the numbers of dendritic cells decline, as does the ability of mice to respond to immunizations. When immunizations are initiated within the period of augmented dendritic cell activation, mice develop anti-tumor responses that show increased durability as well as magnitude, and this approach leads to improved survival in experiments with mice bearing established tumors as well as in a spontaneous melanoma model. We conclude that irradiation can produce potent immune adjuvant effects independent of its ability to induce tumor ablation, and that the timing of immunization and lymphocyte infusion in the irradiated host are crucial for generating optimal anti-tumor immunity. Clinical strategies using these approaches must therefore optimize such parameters, as the correct timing of infusion and vaccination may mean the difference

EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

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Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

2013-01-01

Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

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Zawaski, Janice A. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Gaber, M. Waleed, E-mail: gaber@bcm.edu [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States); Sabek, Omaima M. [Department of Surgery, Methodist Hospital Research Institute, Houston, TX (United States); Wilson, Christy M. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Duntsch, Christopher D. [Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN (United States); Merchant, Thomas E. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Department of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, TN (United States)

2012-03-01

Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results: The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.

Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth

International Nuclear Information System (INIS)

Tsai, C.-S.; Chen, F.-H.; Wang, C.-C.; Huang, H.-L.; Jung, Shih-Ming; Wu, C.-J.; Lee, C.-C.; McBride, William H.; Chiang, C.-S.; Hong, J.-H.

2007-01-01

Purpose: To investigate the effects of single and fractionated doses of radiation on tumors and tumor-associated macrophages (TAMs), and to elucidate the potential of TAMs to influence tumor growth. Methods and Materials: A murine prostate cell line, TRAMP-C1, was grown in C57Bl/6J mice to 4-mm tumor diameter and irradiated with either 25 Gy in a single dose, or 60 Gy in 15 fractions. The tumors were removed at the indicated times and assessed for a variety of markers related to TAM content, activation status, and function. Results: In tumors receiving a single radiation dose, arginase (Arg-I), and cycloxygenase-2 (COX-2) mRNA expression increased as a small transient wave within 24 h and a larger persistent wave starting after 3 days. Inducible nitric oxide synthase (iNOS) mRNA was elevated only after 3 days and continued to increase up to 3 weeks. After fractionated irradiation, Arg-1 and COX-2 mRNA levels increased within 5 days, whereas iNOS was increased only after 10 fractions of irradiation had been given. Increased levels of Arg-I, COX-2, and, to a lesser extent, iNOS protein were found to associate with TAMs 1-2 weeks after tumor irradiation. Function of TAMs were compared by mixing them with TRAMP-C1 cells and injecting them into mice; TRAMP-C1 cells mixed with TAMs from irradiated tumors appeared earlier and grew significantly faster than those mixed with TAMs from unirradiated tumors or TRAMP-C1 alone. Conclusions: Tumor-associated macrophages in the postirradiated tumor microenvironment express higher levels of Arg-1, COX-2, and iNOS, and promote early tumor growth in vivo

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

International Nuclear Information System (INIS)

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

1983-01-01

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

Effects of IL-6 on proliferation and apoptosis of tumor cells multi-irradiated for tumor-bearing mice

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Yongbiao, Liu [Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Applied Physics; Xuzhou Medical Univ., Xuzhou (China); Side, Yao [Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Applied Physics; Kai, Mei; Ying, Liu; Jie, Zhao; Xianwen, Zhang; Qiang, Zhou; Xingzhi, Hao [Xuzhou Medical Univ., Xuzhou (China)

2004-05-15

A study was carried out on effects of IL-6 on the proliferation and apoptosis of tumor cells and the expression of apoptosis relevant genes (p53, bcl-2) in tumor cells for three kinds of fractional total-body-irradiated tumor-bearing mice. The apoptotic index, proliferative index, S phase fraction of S{sub 180} sarcoma, H{sub 22} hepatocarcinoma and Lewis lung cancer cells were measured by flowcytometry (FCM) after total-body-irradiation and irradiation plus IL-6. The protein expression level of p53, bcl-2 in three kinds of tumors was also determined by the immunohisto-chemical method (UltraSensitive S-P). The results showed that the S phase fraction and proliferation index in Lewis lung cancer cells were lower in the irradiated plus IL-6 group than in the control, while apoptotic index was higher (P<0.05). However, the experimental results for S{sub 180} sarcoma cells were opposite (P<0.01). In addition, no significant effects were observed in H{sub 22} hepatocarcinoma. These results revealed that IL-6 promoted the apoptosis of irradiated Lewis lung cancer cells (P<0.05), while the apoptosis of S{sub 180} sarcoma (P<0.05) was restrained, and there was no significant effects on the cellular cycle of H{sub 22} hepatocarcinoma (P>0.05). In Lewis lung cancer the expression level of p53 was lower in the IL-6 group and higher in S{sub 180} sarcoma (P<0.05), while unvaried in H{sub 22} hepatocarcinoma as compared with the control (P>0.05). It is considered that tumor cell's proportion in the cellular cycle is changed by IL-6 and the effects of IL-6 on the expression of p53, bcl-2 in different three kinds of tumors are different. IL-6 has radio-sensitive effects on some tumors and opposite effects on other tumors, it may be related to the expression of p53 and bcl-2 in tumor cells. (authors)

Incidence and nature of tumors induced in Sprague-Dawley rats by gamma-irradiation

International Nuclear Information System (INIS)

Gross, L.; Dreyfuss, Y.; Faraggiana, T.

1988-01-01

In our previous studies carried out on inbred rats of the Sprague-Dawley strain, the tumor incidence was increased following irradiation (150 rads, 5 times, at weekly intervals), from 22 to 93% in females and from 5 to 59% in males. Experiments here reported suggest that 2 consecutive total-body gamma-irradiations of 150 rads each are sufficient to induce in rats the development of tumors, some malignant; 18 of 19 females (94.7%) developed tumors at an average age of 11.4 mo, and seven of the 14 males in this group (50%) developed tumors at an average age of 10.4 mo. In the second group, which received 3 consecutive gamma-irradiations, 20 of 23 females (86.9%) and 5 of 13 males (38.4%) developed tumors at average ages of 9.1 and 7.5 mo, respectively. In the third group, among rats which received 4 consecutive gamma-irradiations, 17 of 19 females (89.4%) and 4 of 12 males (33.3%) developed tumors at average ages of 9.4 and 10.5 mo, respectively. The etiology of tumors either developing spontaneously or induced by irradiation in rats remains to be clarified. Our attempts to detect virus particles by electron microscopy in such tumors or lymphomas have not been successful. As a working hypothesis, we are tempted to theorize that tumors or lymphomas developing spontaneously or induced by gamma irradiation in rats are caused by latent viral agents which are integrated into the cell genome and are cell associated, i.e., not separable from the rat tumor cells by conventional methods thus far used

Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

International Nuclear Information System (INIS)

Helbig, Linda; Koi, Lydia; Brüchner, Kerstin; Gurtner, Kristin; Hess-Stumpp, Holger; Unterschemmann, Kerstin; Pruschy, Martin

2014-01-01

Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD 50 ) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P 50 , with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD 50 . Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of radiation response. Whether this mechanism contributes to the improved outcome of fractionated chemoradiation therapy warrants further investigation

Monoclonal antibodies reactive with common tumor antigens on UV-induced tumors also react with hyperplastic UV-irradiated skin

International Nuclear Information System (INIS)

Spellman, C.W.; Beauchamp, D.A.

1986-01-01

Most murine skin tumors induced by ultraviolet light (UVB, 280-340 nm) can be successfully transplanted only into syngeneic hosts that have received subcarcinogenic doses of UVB. The tumor susceptible state is long-lived and mediated by T suppressor cells that control effector responses against common antigens on UV-induced tumors. Because antigen specific suppression arises prior to the appearance of a tumor, questions arise about the source of the original antigen. They have previously reported transplantation studies indicating that UV-irradiated skin is antigenically cross-reactive with UV-induced tumors. They now report on flow cytometry analyses showing that a series of MoAb reactive with common antigens expressed by UV-induced tumors are also reactive on cells from UV-irradiated skin. Various antigens appear at different times in the UV irradiation scheme, and some persist while others are transient. They speculate that the common antigens detected may be the ones to which functional suppression is directed. If true, these results suggest that successful tumors need not escape host defenses to emerge. Rather, tumors may arise and grow progressively if they express antigens that cross-react with specificities to which the host has previously mounted a suppressive response

Extracorporeal irradiation for malignant bone tumors

International Nuclear Information System (INIS)

Hong, Angela; Stevens, Graham; Stalley, Paul; Pendlebury, Susan; Ahern, Verity; Ralston, Anna; Estoesta, Edgar; Barrett, Ian

2001-01-01

Purpose: Extracorporeal irradiation (ECI) has been used selectively in the management of primary malignant bone tumors since 1996. We report our techniques for ECI and the short-term oncologic and orthopedic outcomes. Methods and Materials: Sixteen patients with primary malignant bone tumors were treated with ECI from 1996 to 2000. The median age was 14 years. The histologic diagnoses were Ewing's sarcoma (11), osteosarcoma (4) and chondrosarcoma (1). The treated sites were femur (7), tibia (4), humerus (2), ilium (2), and sacrum (1). Following induction chemotherapy in Ewing's sarcomas and osteosarcoma, en bloc resection of the tumor and tumor-bearing bone was performed. A single dose of 50 Gy was delivered to the bone extracorporeally using either a linear accelerator (9 cases) or a blood product irradiator (7 cases). The orthopedic outcome was recorded using a standard functional scale. Results: At a median follow-up of 19.5 months, there were no cases of local recurrence or graft failure. One patient required amputation due to chronic osteomyelitis. For the 10 patients with follow-up greater than 18 months, the functional outcomes were graded good to excellent. Conclusion: The short-term oncologic and orthopedic results are encouraging and suggest that ECI provides a good alternative for reconstruction in limb conservative surgery in selected patients. This technique should only be used in a multidisciplinary setting, where careful follow-up is available to assess the long-term outcomes

Effect of immunomodifier on radiation-induced antitumor immunity following local irradiation to tumor, 2

International Nuclear Information System (INIS)

Mukae, Shiro; Norimura, Toshiyuki; Tsuchiya, Takehiko

1988-01-01

This study was carried out to clarify whether or not the antitumor cell-mediated immunity of host is more effectively induced by the combined use of mouse interferon-α/β (MuIFN-α/β) with local irradiation than by simple local irradiation to tumor. C3H/He female mice, MM46 tumor cells and mouse interferon-α/β (MuIFN-α/β) were used in the experiment. Antitumor activity in mice was evaluated by the inhibition of tumor growth and mean survival days after treatment. Spleen cell killing activity to MM46 tumor cells was measured to evaluate the antitumor activity in vitro. In the case of single use of MuIFN-α/β, tumor growth was more rapid than in the non-treated group (control) in vivo. The mean survival days were also reduced. There was no siginificant difference in tumor growth inhibition between combined therapy using X-irradiation and MuIFN-α/β, and single therapy by local irradiation. However, in the case of administration of MuIFN-α/β after irradiation, the mean survival days was significantly increased compared with the group receiving X-ray irradiation only. (author)

Tumor oxygenation in a transplanted rat rhabdomyosarcoma during fractionated irradiation

International Nuclear Information System (INIS)

Zywietz, Friedrich; Reeker, Wolfram; Kochs, Eberhard

1995-01-01

Purpose: To quantify the changes in tumor oxygenation in the course of a fractionated radiation treatment extending over 4 weeks. Methods and Materials: Rhabdomyosarcomas R1H of the rat were irradiated with 60 Co-γ-rays with a total dose of 60 Gy, given in 20 fractions over 4 weeks. Oxygen partial pressure (pO 2 ) in tumors was measured at weekly intervals using polarographic needle probes in combination with a microprocessor-controlled device (pO 2 -Histograph/KIMOC). The pO 2 measurements were carried out in anesthetized animals under mechanical ventilation and in respiratory and hemodynamic steady state. Tumor pO 2 values were correlated to the arterial oxygen pressure p a O 2 , arterial pCO 2 , and pH determined with a blood gas analyzer. Results: Tumor oxygenation did not change significantly during the 3 weeks of irradiation (up to 45 Gy), from a median pO 2 of 23 ± 2 mmHg in untreated controls to 19 ± 4 mmHg after the third week. The decrease of the number of pO 2 values between 0 and 5 mmHg indicated that an improved oxygenation in the tumors occurred. However, with increasing radiation dose (fourth week, 60 Gy) a significant decrease in tumor oxygenation to a median pO 2 of 8 ± 2 mmHg and a rapid increase in the frequency of pO 2 values (35 ± 4%) between 0 and 5 mmHg was found. Conclusion: Improved oxygenation in rhabdomyosarcomas R1H was only present in the early phase of the fractionated irradiation. Radiation doses above 45 Gy led to a considerable decrease of tumor oxygenation in the later phase of irradiation

Origin of malignant tumors of the upper respiratory and digestive tracts and the ear. Pt. 4. Malignant tumors caused by irradiation. B. Special part

Energy Technology Data Exchange (ETDEWEB)

Leicher, H [Mainz Univ. (Germany, F.R.). Hals-, Nasen- und Ohrenklinik

1979-12-01

The problem of radiation induced tumors is explained in detail in the following chapters: 1. Malignant tumors in dial painters using luminous paint, 2. Malignant tumors after injection of Thorotrast, 3. Bronchial tumors in Uran-mineworkers, 4. Malignant tumors caused by radium-compresses and radium-moulages, 5. Thyroid cancer caused by irradiation, 6. Leukemia and malignant tumors following the atomic bomb detonation in Hiroshima and Nakasaki, 7. Malignant tumors in Lupus vulgaris, 8. Development of malignant tumors following the irradiation of praecancerous alterations, of benign tumors and other benign changes in head and neck, 9. Radiation induced soft-tissue and bone sarcoma in the skull, 10. Radiation-induced cancers in hypopharynx diverticula, 11. Radiation-induced cancers in the antethoracic skin graft esophagus, 12. Radiation-induced second-tumors, 13. Cancer caused by ultraviolet rays, 14. Increase of hematogenic metastases by irradiation. 15. Malignant tumors caused by irradiation of the fetus in utero.

The separation of a mixture of bone marrow stem cells from tumor cells: an essential step for autologous bone marrow transplantation

International Nuclear Information System (INIS)

Rubin, P.; Wheeler, K.T.; Keng, P.C.; Gregory, P.K.; Croizat, H.

1981-01-01

KHT tumor cells were mixed with mouse bone marrow to simulate a sample of bone marrow containing metastatic tumor cells. This mixture was separated into a bone marrow fraction and a tumor cell fraction by centrifugal elutriation. Elutriation did not change the transplantability of the bone marrow stem cells as measured by a spleen colony assay and an in vitro erythroid burst forming unit assay. The tumorogenicity of the KHT cells was similarly unaffected by elutriation. The data showed that bone marrow cells could be purified to less than 1 tumor cell in more than 10 6 bone marrow cells. Therefore, purification of bone marrow removed prior to lethal radiation-drug combined therapy for subsequent autologous transplantation appears to be feasible using modifications of this method if similar physical differences between human metastatic tumor cells and human bone marrow cells exist. This possibility is presently being explored

Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

Directory of Open Access Journals (Sweden)

Michal Lotem

2016-01-01

Full Text Available Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p=0.0001 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2, MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p=0.007. Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.

Combined effect of carcinogenic n-nitrosodimethylamine precursors and fractioned γ-irradiation on tumor development in rats

International Nuclear Information System (INIS)

Galenko, P.M.; Nedopitanskaya, N.N.

1996-01-01

The influence of combined action of N-nitrosodimethylamine (NDMA) and fractioned γ-irradiation on tumor development in rats was investigated. Both the tumor frequency and tumor plurality coefficient have been studied for two types of treatment: precursors of NDMA (amidopyrine and/or sodium nitrite (SN)) alone and the combination 'precursors plus radiation'. Tumor frequency decreased by about 11% after combination of γ-irradiation and precursors in comparison with precursors alone. Nevertheless, treatment with SN and γ-irradiation did not change tumor frequency in comparison with SN alone. Irradiation of rats treated with precursors led to an increased tumor plurality coefficient

Proliferation and Differentiation of Autologic and Allogenic Stem Cells in Supralethally X-Irradiated Dogs

Energy Technology Data Exchange (ETDEWEB)

Chertkov, I. L. [Department of Radiobiology, Central Institute of Haematology and Blood Transfusion, Moscow, USSR (Russian Federation)

1967-07-15

Full text: Allogenic bone marrow after transplantation into dogs irradiated with 1000 R X-rays differentiates in the normal way only for 3-4 days, afterwards transforming into lymphoid cells. This transformation is due to the antigen stimulus of the host on the grafted stem cells. The lymphoid cells, obtained from the host's blood on the 7-8th day after grafting, showed specific, immune activity under the Immune Lymphocyte Transfer test. Within a short duration of the immune response immunoblasts and immunocytes Undergo degenerative changes: destroyed mitochondria, formation of autophagic vacuoles and, finally, lysis of the cells. These changes are suggested to be the result of overloading of immune cells with antigen. Preliminary sensitization of the donor with prospective host's haemopoietic tissue does not hasten the immune transformation of haemopoiesis. Injections of bacterial pyrogen, cortisone or 6-mercaptopurine into recipients, as well as incubation of bone marrow at 37 Degree-Sign C for 2 hours, do not prevent the immune transformation. Preliminary thymectomy of the prospective recipients prevents in some of the cases immune transformation of the bone-marrow graft. The delay of allogenic bone-marrow transplantation for 5-6 days prevents in some dogs (X-irradiated with 1000 R, but not with 1200 R) the immune transformation. Transplantation of autologic bone marrow or shielding of the legs during irradiation is accompanied with good restoration of normal haemopoiesis without lymphoid transformation. (author)

Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

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Helbig, Linda [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Koi, Lydia [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Deutsches Konsortium für Translationale Krebsforschung, Site Dresden, Dresden (Germany); Brüchner, Kerstin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Institute of Radiooncology Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Gurtner, Kristin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Hess-Stumpp, Holger; Unterschemmann, Kerstin [Global Drug Discovery, Bayer Pharma, Berlin (Germany); Pruschy, Martin [Radiation Oncology, University of Zurich, Zurich (Switzerland); and others

2014-01-01

Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of

Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma.

Science.gov (United States)

Eton, O; Kharkevitch, D D; Gianan, M A; Ross, M I; Itoh, K; Pride, M W; Donawho, C; Buzaid, A C; Mansfield, P F; Lee, J E; Legha, S S; Plager, C; Papadopoulos, N E; Bedikian, A Y; Benjamin, R S; Balch, C M

1998-03-01

Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.

Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver.

Science.gov (United States)

Nemunaitis, John; Barve, Minal; Orr, Douglas; Kuhn, Joseph; Magee, Mitchell; Lamont, Jeffrey; Bedell, Cynthia; Wallraven, Gladice; Pappen, Beena O; Roth, Alyssa; Horvath, Staci; Nemunaitis, Derek; Kumar, Padmasini; Maples, Phillip B; Senzer, Neil

2014-01-01

Therapies for advanced hepatocellular carcinoma (HCC) are limited. We carried out a phase I trial of a novel autologous whole-cell tumor cell immunotherapy (FANG™), which incorporates a dual granulocyte macrophage colony-stimulating factor (GM-CSF) expressive/bifunctional small hairpin RNA interference (bi-shRNAi) vector. The bi-shRNAi DNA targets furin, which is a proconvertase of transforming growth factors beta (TGFβ) 1 and 2. Safety, mechanism, immunoeffectiveness, and suggested benefit were previously shown [Senzer et al.: Mol Ther 2012;20:679-689; Senzer et al.: J Vaccines Vaccin 2013;4:209]. We now provide further follow-up of a subset of 8 HCC patients. FANG manufacturing was successful in 7 of 8 attempts (one failure due to insufficient cell yield). Median GM-CSF expression was 144 pg/10(6) cells, TGFβ1 knockdown was 100%, and TGFβ2 knockdown was 93% of the vector-transported cells. Five patients were vaccinated (1 or 2.5×10(7) cells/intradermal injection, 6-11 vaccinations). No FANG toxicity was observed. Three of these patients demonstrated evidence of an immune response to the autologous tumor cell sample. Long-term follow-up demonstrated survival of 319, 729, 784, 931+, and 1,043+ days of the FANG-treated patients. In conclusion, evidence supports further assessment of the FANG immunotherapy in HCC. © 2014 S. Karger AG, Basel.

Relationship between α/β and radiosensitivity and biologic effect of fractional irradiation of tumor cells

International Nuclear Information System (INIS)

Guo Chuanling; Chinese Academy of Sciences, Beijing; Wang Jufang; Jin Xiaodong; Li Wenjian

2006-01-01

Five kinds of malignant human tumor cells, i.e. SMMC-7721, HeLa, A549, HT29 and PC3 cell lines, were irradiated by 60 Co γ-rays to 1-6 Gy in a single irradiation or two irradiations of half dose. The radiosensitivity was compared with the dose-survival curves and D 50 and D 10 values. Differences in the D 50 and D 10 between the single and fractional irradiation groups showed the effect of fractional irradiation. Except for PC3 cells, all the cell lines showed obvious relationship between radiosensitivity and biologic effect of fractional irradiation and the α/β value. A cell line with bigger α/β was more radiation sensitive, with less obvious effect of fractional irradiation. The results indicate that there were obvious differences in radiosensitivity, repair ability and biologic effect of fractional irradiation between tumor cells from different tissues. To some tumor cell lines, the relationship between radiosensitivity, biologic effect of fractional irradiation and repair ability was attested. The α/β value of single irradiation can be regarded as a parameter to investigate the radiosensitivity and biologic effect of fractional irradiation of tumor cells. (authors)

Repair of potentially lethal and sublethal radiation damage in x-irradiated ascites tumor cells

International Nuclear Information System (INIS)

Tsuboi, Atsushi; Okamoto, Mieko; Tsuchiya, Takehiko.

1985-01-01

The ability of cells to repair cellular radiation damage during the growth of TMT-3 ascites tumor and the effect of host reaction on the repair ability were examined by using an in vitro assay of cell clonogenicity after in situ irradiation of tumor cells. In single-dose experiments, the repair of potentially lethal radiation damage (PLD) was observed in stationary phase cells (12-day tumor) of the unirradiated host, but not in exponential phase cells (3-day tumor) of the unirradiated host animals. However, if previously irradiated host animals were used, even the exponentially growing tumor cells showed repair of PLD. In two-dose experiments, the ability to repair sublethal radiation damage (SLD) in exponential phase tumor cells was less than that of stationary phase cells in the unirradiated host. In the pre-irradiated host, the extent of the repair in exponential phase cells was somewhat enhanced. These results suggest that irradiation of host animals might suppress a factor that inhibits repair, resulting in enhancement of the repair capability of tumor cells. (author)

Irradiation combined with SU5416: Microvascular changes and growth delay in a human xenograft glioblastoma tumor line

International Nuclear Information System (INIS)

Schuuring, Janneke; Bussink, Johan; Bernsen, Hans; Peeters, Wenny; Kogel, Albert J. van der

2005-01-01

Purpose: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. Methods and materials: A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. Results: SU5416, when combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. Conclusions: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone

Effect of x irradiation on the vascularization of experimental animal tumors

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Saeki, Y; Ogawa, F; Nishiguchi, H; Tanaka, N; Murakami, K [Kyoto Prefectural Univ. of Medicine (Japan)

1975-03-01

The authors studied the effect of ionizing radiation on blood vessels and tumor growth in two animal tumor systems: a third generation isoplants of a mammary cancer and a spontaneously arising squamous cell carcinoma. Single cell suspensions were transplanted into a C3H and a C3Hf mouse respectively. They were irradiated once with 2000 rad when the tumors reached about 8 mm in diameter. Microangiography was performed at a constant temperature and pressure, and a contrast medium containing lead-oxide and gelatin was flushed the vena cava for 10 min. at 120 mmHg. Tumor shrinkage was followed by continuous regrowth. The basic vasculature of the mammary carcinoma consisted of abundant large and fine blood vessels corkscrewed or stretched from the periphery of the tumor to its center in complex reticular networks. One day after irradiation there were small scattered avascular areas which, by the third day formed a large central necrosis. Supervascularization was also observed, indicating that some hypoxic tumor cells could be reoxygenized. In 5 days vascularization was similar to that of a nonirradiated tumor. Conversely, The squamous cell carcinoma showed peripheral and central vascularization with abundant vascular and avascular areas and extravasion in the large avascular area. Two days after irradiation the vessels were dilated. At 3 days peripheral fine vessels were damaged but the central vasculature remained intact. Unlike the mammary carcinoma, supervascularization was not the typical finding. At 5 days, vascularization was similar to that of a nonirradiated tumor.

Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

Directory of Open Access Journals (Sweden)

Moritz Palmowski

2009-09-01

Full Text Available Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1 and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

Changes of natural killer activity following local 60Co irradiation in intracranial tumor-bearing mice

International Nuclear Information System (INIS)

Otsuka, Shin-ichi; Suda, Kinya; Yamashita, Junkoh; Takeuchi, Juji; Handa, Hajime

1982-01-01

Changes of natural killer activity (NK activity) by local 60 Co irradiation in intracranial tumor-bearing mice were studied by the method of 51 Cr release assay. Local irradiation was administered 10 days after intracranial transplantation of 203-Glioma which had been originally induced by 20-methylcholanthrene in C57BL mice. Irradiation suppressed the growth of tumor and prolonged the mean survival time. The 50% survival time of untreated mice was about 2.5 weeks but that of mice treated by a single dose of 1000 rad and 1500 rad of irradiation was about 4.5 weeks and 6.5 weeks respectively. NK activity of spleen cells in these mice was serially examined. NK activity was gradually increased in mice treated by local irradiation, while it was gradually decreased in mice without treatment. On the other hand, NK activity remained unchanged in non-tumor-bearing control mice. Mice treated with 1000 rad and 1500 rad of irradiation showed 44.0% and 47.6% of % specific 51 Cr release respectively 11 days after irradiation while normal mice showed 18.0%. The increased NK activity after local irradiation suggested that local irradiation might have enhanced the immunological defence mechanisms against the tumor in the tumor-bearing hosts. Some characteristics of effector cells in this assay system were examined. The cytotoxicity of spleen cells was removed by the treatment of anti-BAT serum and complement but was not removed by the treatment of anti-Thy-1.2 serum and complement. Since NK activity reflects the immunological resistance to tumors to some extent, it is felt important to clarify the significance of changes of NK activity in patients with brain tumors in relation to various treatments including surgery, radiotherapy, chemotherapy and immunotherapy in the next step. (author)

Effects of perfluorochemical emulsion on the timing of administration and irradiation in tumor bearing mice

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Hishikawa-Itoh, Youko; Ayakawa, Yoshio; Miyata, Nobuki

1988-01-01

Perfluorochemical content was examined periodically, in blood, tumor and some organs using gas chromatography, after Fluosol-DA saline 20 % (FDAS) was injected into LLC bearing mice. The blood half-life of FDAS in LLC bearing mice was 3.76 hrs (5 ml/kg injection) or 6.15 hrs (20 ml/kg injection) respectively, and FDAS almost disapeared from the blood after about 2 days (5 ml/kg) and 3 days (20 ml/kg) of FDAS-injection. Most of FDAS was accumulated into spleen and the liver. FDAS accumulation into the tumor tissue was 1 ∼ 6 % of injected-FDAS dose and the peak of FDAS accumulation was 1 ∼ 3 days after injection. The timing of FDAS-injection and irradiation in tumor bearing mice determined according to the results above (half-life and accumulation of FDAS in tumor). FDAS (5, 10, 20 ml/kg) was injected to LLC-bearing mice on 3, 2, 1 and 0 day before irradiation and they were irradiated 15 Gray under oxygen-breathing, respectively. FDAS-injected groups before irradiation (3, 2, 1 day before, respectively) showed a tendency of tumor growth delay, but didn't show significant difference as compared with oxygen-breathing group without FDAS, because they had not enough effective FDAS content in the blood. Although the FDAS-injected groups just before irradiation significantly showed the delay of tumor growth. These results demonstrate that oxygen and FDAS existing in the blood injected just before irradiation effectively delay tumor growth in which the lowest effective dose is 5 ml/kg. In the case of clinical application of FDAS, FDAS may be most effective, when administrated just before irradiation in every fractionated irradiation. (author)

Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation

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Kocher, M.; Treuer, H.

1995-01-01

A 3-dimensional computer simulation was developed in order to estimate the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells during a full course of fractionated irradiation. The growth of a small tumor situated in a vascularized stroma with 350 capillary cross-sections/mm 3 which were displaced by the growing tumor was simulated. Tumors contained 10 4 cells when irradiation started, intrinsic radiosensitivity was set to either low (α=0.3 Gy -1 , β=0.03 Gy -2 ) or high (α=0.4 Gy -1 , β=0.04 Gy -2 ) values. Oxygen enhancement ratio was 3.0, potential tumor doubling time T pot =1, 2 or 5 days. A simulated fractionated radiotherapy was carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence or absence of factors preventing tumor cord shrinkage was also included. During the growth phase, all tumors developed a necrotic core with a hypoxic cell fraction of 25% under these conditions. During irradiation, the slower growing tumors (T pot =2 to 5 days) showed complete reoxygenation of the hypoxic cells after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30 to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were enough in order to sterilize the tumors in these cases. In the fast growing tumors (T pot =1 day), reoxygenation was only observed in the case of high radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation increased the control rates by up to 60%. (orig./MG) [de

Independent occurence of gastric tumor and intestinal metaplasia by x-irradiation

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Watanabe, Hiromitsu; Ito, Akihiro

1986-01-01

The selective occurence of gastric tumors and intestinal metaplasias in the stomach by X-irradiation were described both in mice and rats. The appearance of both lesions was greatly influenced by animal's strains in both species and also by the sex in rats. A few gastric tumors were observed in the animals given a high does with spilt into low doses of X-irradiation. The adequate dose for gastric tumorigenesis may be around 20 Gy in mice and 15 Gy in rats. A good relationship between X-ray dose and incidence of gastric tumor was observed in ICR mice. Frequency of intestinal metaplasia by X-irradiation was much higher in rats compared to that in mice. X-ray dose requested for moderate and induction of intestinal metaplasia was decreased with a dose which was induced erosion and gastric tumor. It has been empirically clarified that an elevation of pH value in the gastric juice is one of the principal factors responsible for the development of intestinal metaplasia in the gastric mucosa among the conditions thus for introduced. In this article, we have introduced the relevant examples about intestinal metaplasia without carcinogenic insult, and the relationship between gastric tumor and intestinal metaplasia were described. The intestinal metaplasia was not always observed within or adjacent to neoplastic gastric glands. A combined treatment of X-ray and MNNG was not effective for gastric tumor and frequency of intestinal metaplasia was inversely related to the incidence of gastric tumors. In conclusion, occurrence of gastric tumor and intestinal metaplasia may be independent, and intestinal metaplasia might not be a prerequite for the occurrence of gastric tumor. (author)

Paranasal sinus tumors: Results of irradiation alone vs. irradiation and surgery

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Shumway, R.C.; Chung, C.T.; Sagerman, R.H.; King, G.A.; Dalal, P.S.

1987-01-01

Forty patients were treated for carcinoma of the paranasal sinuses from 1965 to 1983. Thirteen patients were treated with an integrated program of surgery plus irradiation; and 27 received irradiation alone. Five-year actuarial survival for patients with maxillary antral tumors was 45% (5 of 11) in the combined treatment group and 21% (3 of 14) in the radiation-only group. Local control for the combined treatment group was 73% (8 of 11), compared to 20% (3 of 15) for the radiation-only group (P > .01). Twenty of 24 patients dying of disease had local recurrence. The technical aspects of treatment and a review of the literature are presented

Cross-immunity between syngeneic tumors in mice immunized with gamma-irradiated ascites tumors

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Kudo, Hajime; Waga, Takashi; Sato, Tatsusuke; Ogasawara, Masamichi; Ito, Izumi

1980-01-01

C3H/He mice immunized repeatedly with irradiated (13,000 rads 60 Co) MM46 or MM48, both transplantable ascites mammary carcinomas of the same strain, were subcutaneously challenged with the identical or the different tumor. In mice immunized with irradiated MM46, the growth of challenges of not only MM46 but also MM48 was inhibited. On the other hand, in mice immunized with irradiated MM48, the growth of challenges of MM48 was inhibited, but the inhibition of the growth of MM46 was not observed. Cross-immunity, therefore, was shown by immunization with MM46 but not with MM48. These findings were considered to indicate that MM46 expressed cross-immunity against MM48 because of its high resistance to the irradiation, and that MM48 did not show cross-immunity to MM46 because of its low resistance to the irradiation. (author)

Effects of low dose γ-rays irradiation on yield of tumor-infiltrating lymphocytes in mice

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Zou Huawei; Su Liaoyuan; Tian Hailin

1998-01-01

It is confirmed that low dose irradiation can inhibit tumor growth. In order to know tumor growth inhibiting mechanism, the changes of tumor-infiltrating lymphocytes (TIL) were investigated after exposing to tumor-bring mice. The mice were exposed to different doses, then , EAC cells were transplanted at the 3,6,9 and 24h hour. Ten days later TILs increased obviously caused by of 5-10 cGy γ-rays irradiation. The most obvious increasing occurred in the group in which cells was exposed irradiation for 6 hours at 10 cGy dose. A low dose radiation can make the yield of TILs increased. I might be correlated to the mechanism of tumor growth inhibiting

Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

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Torres-Trejo Alejandro

2007-12-01

Full Text Available Abstract Background The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL-4 gene transfected fibroblasts. Methods In University of Pittsburgh Cancer Institute (UPCI protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM or anaplastic astrocytoma (AA received gross total resection (GTR of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. Results and Discussion In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN-γ Enzyme-Linked Immuno-SPOT (ELISPOT assay in another human leukocyte antigen (HLA-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA epitope EphA2883–891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants

Histopathological investigation of radiation necrosis. Coagulation necrosis in the irradiated and non-irradiated brain tumors and in the normal brain tissue

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Nakamura, N [Niigata Univ. (Japan). Brain Research Inst.

1977-01-01

Eighty four irradiated tumors (including 59 gliomas) and the surrounding brain tissue were analyzed. In 'normal' brain tissue, typical coagulation necrosis attributable to irradiation was observed in the cerebral white matter, presenting a whitish-yellow color but no remarkable changes in volume. Histologically there was complete desintegration of myelin and axon. Vascular changes included hyalinous thickening, concentric cleavage, fibrinoid degeneration, adventitial fibrosis and edema of small arteries, fibrin thrombi or occlusion of arterioles and capillaries, and telangiectasia of small veins and venules. While other tumors showed hyalinous or fibrous scar tissue and decrease in volume, the gliomas maintained their original volume without residual tumor cells. Massive coagulation necrosis was occasionally found even in full volume, non-irradiated gliomas (controls), although the changes were fewer and not so varied as in typical radiation necrosis. With small dosages, it was difficult to judge whether the necrosis was caused by irradiation or occurred spontaneously. Coagulation necrosis in tumor tissue was found in 25 of 59 cases (42%) of irradiated gliomas, but in only 2 of 49 cases (4%) of the nonirradiated gliomas. In 49 cases no coagulation necrosis of the surrounding tissue was found. Although histopathological judgement is difficult, it is suggested that there is a significant correlation between coagulation necrosis and irradiation. Discussion of the relationship between coagulation necrosis and NSD (nominal standard dose) led to the conclusion that coagulation necrosis will not be caused by irradiation of less than 1400 rets in NSD.

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

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

2001-01-01

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

Change of cell cycle arrest of tumor cell lines after 60Co γ-irradiation

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Tang Yi; Liu Wenli; Zhou Jianfeng; Gao Qinglei; Wu Jianhong

2003-01-01

Objective: To observe the cell cycle arrest changes in peripheral blood mononuclear cells (PBMNCs) of normal persons and several kinds of tumor cell lines after 60 Co γ-irradiation. Methods: PBMNCs of normal persons, HL-60, K562, SiHA and 113 tumor cell lines were irradiated with 60 Co γ-rays at the absorbed doses of 6, 10,15 Gy. Cell cycles changes were checked 6, 12, 24, 48 and 60 h after the irradiation. Results: A stasis state was observed in normal person PBMNCs, 95 percents of which were in G 1 phase, and they still remained stasis after the irradiation. Except the 113 cell line manifesting G 1 phase arrest, all other tumor cell lines showed G 2 /M phase arrest after irradiation. The radiation sensitivity of HL-60 was higher than that of SiHA cell line. Conclusion: Different cell lines have different cell cycle arrest reaction to radiation and their radiation sensitivity are also different

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients

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Ellebaek Eva

2012-08-01

Full Text Available Abstract Background Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL, in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. Methods This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625 including patients with metastatic melanoma, PS ≤1, age Results Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months, 2 patients had stable disease (4 and 5 months and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Conclusion Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.

Study of B7.1 costimulatory molecule neoexpression induced by γ irradiation of different dose in various human tumor cells

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Zhou Jianghua; Su Liaoyuan; Tong Jian; Zhu Minqing; Xue Lian

2001-01-01

The relationship between irradiation and B7.1 co-stimulative molecule expression of human tumor cells was studied to explore the reason of enhanced tumor cells immunity. The effect of γ ray irradiation on B7.1 molecule expression in various human tumor cells which were irradiated with 30 Gy, 40 Gy, 50 Gy, 60 Gy γ ray was investigated. At 24 h, 48 h, 72 h and 96 h after irradiation the changes of B7.1 molecule was measured by flow cytometry (FCM) with immunofluorescence technique. The activation of lymphocyte toxin upon tumor target cell after exposure was determined by using radiation release method. The results showed that a few of tumor cells after γ-ray irradiation express B7.1 co-stimulative molecule. Furthermore, B7.1 molecule membrane expression after γ ray irradiation is shown to enhance the activation of lymphocyte toxin. The data could explain the enhanced immunogenicity of tumor cells after irradiation, and could lead to new immunotherapy protocols. The experiments suggested that γ ray irradiation could induce human tumor cells to express B7.1 co-stimulative molecules and enhance tumor cell immunity

Migration inhibition of immune mouse spleen cells by serum from x-irradiated tumor-bearing mice

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Moroson, H.

1978-01-01

Tumor-specific antigens of the chemically induced MC 429 mouse fibrosarcoma were detected in a 3 M KCl extract of tumor by the inhibition of migration of specifically immune spleen cells. Using this assay with serum from tumor-bearing mice no tumor antigen was detected in serum of mice bearing small tumors, unless the tumor was exposed to local x irradiation (3000 R) 1 day prior to collection of serum. It was concluded that local x irradiation of tumor caused increased concentration of tumor antigen in the serum. When the tumor was allowed to grow extremely large, with necrosis, then host serum did cause migration inhibition of both nonimmune and immune spleen cells. This migration-inhibition effect was not associated with tumor antigen, but with a nonspecific serum factor

Anti-tumor effect of total body irradiation of low doses on WHT/Ht mice

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Miyamoto, Miyako; Sakamoto, Kiyohiko

1987-01-01

The effect of low dose (0.05 - 1.0 Gy) of total body irradiation (TBI) on non-tumor bearing and tumor bearing mice were investigated. Mice received TBI of 0.1 Gy during 6 - 12 hours before tumor cell inoculation demonstrated to need larger number of tumor cells (approximately 2.5 times) for 50 per cent tumor incidence, compared to recipient mice not to receive TBI. On the other hand, in tumor bearing mice given 0.1 Gy of TBI only tumor cell killing effect was not detected, however enhancement of tumor cell killing effect and prolonged growth delay were observed when tumor bearing mice were treated with 0.1 Gy of TBI in combined with local irradiation on tumors, especially cell killing effect was remarkable in dose range over 6 Gy of local exposure. The mechanism of the effect of 0.1 Gy TBI is considered to be host mediated reactions from the other our experimental results. (author)

Enhancement of the efficacy of x-irradiation by pentobarbital in a rodent brain-tumor model

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Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H.

1990-01-01

Radiation therapy is an important component of brain tumor treatment, but its efficacy is limited by its toxicity to the surrounding normal tissue. Pentobarbital acts as a cerebral radioprotectant, but the selectivity of its protection for the central nervous system has not been demonstrated. To determine if pentobarbital also protects tumor against ionizing radiation, five groups of Fischer 344 rats were observed after exposure to varying combinations of the presence or absence of implanted tumor, pentobarbital, and radiation treatment. The first three groups underwent cerebral implantations of a suspension of 9L gliosarcoma cells. Group 1 was left untreated and served as tumor-bearing controls. Group 2 received 30 Gy of whole-brain x-irradiation without anesthesia 8 days after tumor implantation. Group 3 received the same radiation treatment 15 minutes after pretreatment with 60 mg/kg of pentobarbital intraperitoneally. Groups 4 and 5 served as radiation controls, receiving 30 Gy of x-irradiation while awake and 30 Gy of x-irradiation after pentobarbital administration, respectively. Survival was calculated from the death of the last tumor-bearing rat. The mean survival time in tumor-bearing control rats was 20.8 +/- 2.6 days (+/- standard deviation). X-irradiation alone significantly enhanced the period of survival in rats implanted with the 9L tumor (29.7 +/- 5.6 days, p less than 0.03). Further significant prolongation of survival was seen with the addition of pentobarbital to the treatment regimen (39.9 +/- 13.5 days, p less than 0.01). Nontumor-bearing rats irradiated while awake (Group 4) survived 30.9 +/- 2.3 days. All of their pentobarbital-anesthetized counterparts in Group 5 survived. If pentobarbital had offered radioprotection to the tumor, then Group 3 would have had a shorter survival period than Group 2

Complications from high-dose para-aortic and pelvic irradiation for malignant genitourinary tumors

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Komaki, R.; Barber-Derus, S.; Glisch, C.; Lawton, C.A.; Cox, J.D.; Wilson, J.F.

1986-01-01

Between 1967 and 1982, 59 patients (33 with gynecologic malignancies and 26 with malignant tumors of the genitourinary system) received irradiation of 40 Gy or more for metastases to the para-aortic lymph nodes, in addition to pelvic irradiation. Disease in the para-aortic lymph nodes was controlled in 50 patients; the treatment failed in nine. Moderately acute side effects were seen in 25 patients, but none was severe. Late effects of irradiation were moderate in five patients and severe in three. Thirty patients are alive at 5 years. The benefits of local control and prolonged disease-free survival appear to outweigh considerably the risk of late effects from pelvic and para-aortic irradiation for advanced malignant tumors of the genitourinary system

Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity

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Campana Dario

2010-10-01

Full Text Available Abstract Background The possibility that autologous NK cells could serve as an effective treatment modality for solid tumors has long been considered. However, implementation is hampered by (i the small number of NK cells in peripheral blood, (ii the difficulties associated with large-scale production of GMP compliant cytolytic NK cells, (iii the need to activate the NK cells in order to induce NK cell mediated killing and (iv the constraints imposed by autologous inhibitory receptor-ligand interactions. To address these issues, we determined (i if large numbers of NK cells could be expanded from PBMC and GMP compliant cell fractions derived by elutriation, (ii their ability to kill allogeneic and autologous tumor targets by direct cytotoxitiy and by antibody-mediated cellular cytotoxicity and (iii defined NK cell specific receptor-ligand interactions that mediate tumor target cell killing. Methods Human NK cells were expanded during 14 days. Expansion efficiency, NK receptor repertoire before and after expansion, expression of NK specific ligands, cytolytic activity against allogeneic and autologous tumor targets, with and without the addition of chimeric EGFR monoclonal antibody, were investigated. Results Cell expansion shifted the NK cell receptor repertoire towards activation and resulted in cytotoxicity against various allogeneic tumor cell lines and autologous gastric cancer cells, while sparing normal PBMC. Blocking studies confirmed that autologous cytotoxicity is established through multiple activating receptor-ligand interactions. Importantly, expanded NK cells also mediated ADCC in an autologous and allogeneic setting by antibodies that are currently being used to treat patients with select solid tumors. Conclusion These data demonstrate that large numbers of cytolytic NK cells can be generated from PBMC and lymphocyte-enriched fractions obtained by GMP compliant counter current elutriation from PBMC, establishing the preclinical

How does ionizing irradiation contribute to the induction of anti-tumor immunity?

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Yvonne eRubner

2012-07-01

Full Text Available Radiotherapy (RT with ionizing irradiation is commonly used to locally attack tumors. It induces a stop of cancer cell proliferation and finally leads to tumor cell death. During the last years it has become more and more evident that besides a timely and locally restricted radiation-induced immune suppression, a specific immune activation against the tumor and its metastases is achievable by rendering the tumor cells visible for immune attack. The immune system is involved in tumor control and we here outline how RT induces anti-inflammation when applied in low doses and contributes in higher doses to the induction of anti-tumor immunity. We especially focus on how local irradiation induces abscopal effects. The latter are partly mediated by a systemic activation of the immune system against the individual tumor cells. Dendritic cells are the key players in the initiation and regulation of adaptive anti-tumor immune responses. They have to take up tumor antigens and consecutively present tumor peptides in the presence of appropriate co-stimulation. We review how combinations of RT with further immune stimulators such as AnnexinA5 and hyperthermia foster the dendritic cell-mediated induction of anti-tumor immune responses and present reasonable combination schemes of standard tumor therapies with immune therapies. It can be concluded that RT leads to targeted killing of the tumor cells and additionally induces non-targeted systemic immune effects. Multimodal tumor treatments should therefore tend to induce immunogenic tumor cell death forms within a tumor microenvironment that stimulates immune cells.

How Does Ionizing Irradiation Contribute to the Induction of Anti-Tumor Immunity?

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Rubner, Yvonne; Wunderlich, Roland; Rühle, Paul-Friedrich; Kulzer, Lorenz; Werthmöller, Nina; Frey, Benjamin; Weiss, Eva-Maria; Keilholz, Ludwig; Fietkau, Rainer; Gaipl, Udo S.

2012-01-01

Radiotherapy (RT) with ionizing irradiation is commonly used to locally attack tumors. It induces a stop of cancer cell proliferation and finally leads to tumor cell death. During the last years it has become more and more evident that besides a timely and locally restricted radiation-induced immune suppression, a specific immune activation against the tumor and its metastases is achievable by rendering the tumor cells visible for immune attack. The immune system is involved in tumor control and we here outline how RT induces anti-inflammation when applied in low doses and contributes in higher doses to the induction of anti-tumor immunity. We especially focus on how local irradiation induces abscopal effects. The latter are partly mediated by a systemic activation of the immune system against the individual tumor cells. Dendritic cells are the key players in the initiation and regulation of adaptive anti-tumor immune responses. They have to take up tumor antigens and consecutively present tumor peptides in the presence of appropriate co-stimulation. We review how combinations of RT with further immune stimulators such as AnnexinA5 and hyperthermia foster the dendritic cell-mediated induction of anti-tumor immune responses and present reasonable combination schemes of standard tumor therapies with immune therapies. It can be concluded that RT leads to targeted killing of the tumor cells and additionally induces non-targeted systemic immune effects. Multimodal tumor treatments should therefore tend to induce immunogenic tumor cell death forms within a tumor microenvironment that stimulates immune cells.

Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment

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Hopwood, L.E.; Davies, B.M.; Moulder, J.E.

1990-01-01

RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug-resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate- and 5-fluorouracil-resistant cells, but not the frequency of adriamycin-resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance is seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance

Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis

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Lindhofer Horst

2009-02-01

Full Text Available Abstract Peritoneal carcinomatosis (PC from epithelial tumors is a fatal diagnosis without efficient treatment. Trifunctional antibodies (trAb are novel therapeutic approaches leading to a concerted anti-tumor activity resulting in tumor cell destruction. In addition, preclinical data in mouse tumor models demonstrated the induction of long lasting tumor immunity after treatment with trAb. We describe the induction of anti-tumor specific T-lymphocytes after intraperitoneal administration of trAb in patients with PC. 9 patients with progressive PC from gastric (n = 6 and ovarian cancer (n = 2, and cancer of unknown primary (n = 1 received 3 escalating doses of trAb after surgery and/or ineffective chemotherapy. The trAb EpCAM × CD3 (10, 20, 40 μg or HER2/neu × CD3 (10, 40, 80 μg were applicated by intraperitoneal infusion. Four weeks after the last trAb application, all patients were restimulated by subdermal injection of trAb + autologous PBMC + irradiated autologous tumor cells. Immunological reactivity was tested by analyzing PBMC for specific tumor reactive CD4+/CD8+ T lymphocytes using an IFN-γ secretion assay. In 5 of 9 patients, tumor reactive CD4+/CD8+ T-lymphocytes increased significantly, indicating specific anti-tumor immunity. A clinical response (stable disease, partial regression has been observed in 5 of 9 patients, with a mean time to progression of 3.6 months. Follow-up showed a mean survival of 11.8 months (median 8.0 months after trAb therapy. TrAb are able to induce anti-tumor immunity after intraperitoneal application and restimulation. The induction of long-lasting anti-tumor immunity may provide an additional benefit of the intraperitoneal therapy with trAb and should be further elevated in larger clinical trials.

Late orthopedic effects in children with Wilms' tumor treated with abdominal irradiation

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

1991-01-01

Between 1970 and 1984, 31 children with biopsy-proven Wilms' tumor received nephrectomy, chemotherapy, and abdominal irradiation and were followed beyond skeletal maturity. Three patients (10%) developed late orthopedic abnormalities requiring intervention. Ten children received orthovoltage irradiation, and all cases requiring orthopedic intervention or developing a scoliotic curve of greater than 20 degrees were confined to this group, for a complication frequency of 50%. Those children who developed a significant late orthopedic abnormality (SLOA) as defined were treated to a higher median dose (2,890 cGy) and a larger field size (150 cm2) than those who did not (2,580 cGy and 120 cm2). Age at irradiation, sex, and initial stage of disease did not appear to influence the risk of developing an SLOA. No child who received megavoltage irradiation developed an SLOA despite treatment up to 4,000 cGy or to field sizes of 400 cm2. We conclude that modern radiotherapy techniques rarely lead to significant late orthopedic abnormalities previously associated with abdominal irradiation in children with Wilms' tumor

Mortality of monkeys after exposure to fission neutrons and the effects of autologous bone marrow transplantation

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Broerse, J.J.; Bekkum, D.W. van; Hollander, C.F.; Davids, J.A.G.

1978-01-01

In order to assess the risk of exposure to ionizing radiation in man, and to evaluate the results of therapeutic measures, the mortality of rhesus monkeys irradiated with X-rays and fission neutrons and the effect of autologous bone marrow transplantation have been investigated. The LDsub(50/30d) values for X- and neutron-irradiated monkeys amount to 525 and 260 rad respectively, resulting in an r.b.e. of approximately 2 for the occurrence of the bone marrow syndrome. Protection of the animals by autologous bone marrow transplantation was observed up to doses of 860 rad of X-rays and 440 rad of fission neutrons. After both fission-neutron irradiation and X-irradiation in the lowest range of lethal doses, the bone marrow syndrome was found to occur without the concurrent incidence of the intestinal syndrome. The studies indicate that, for humans accidentally exposed to what would otherwise be lethal doses of fast neutrons, bone marrow transplantation may be beneficial. (author)

Inhibitory mechanism of low-dose, whole-body irradiation with gamma-rays against tumor metastasis

International Nuclear Information System (INIS)

Yasuhiro Ohsima; Mitsutoshi Tukimoto; Shuji Kojima

2007-01-01

Complete text of publication follows. A lot of beneficial effects of low-dose irradiation are well known. Of them, an inhibitory effect of the radiation on lung metastasis is reported so far. It has been reported that low-dose whole-body irradiation with gamma rays enhanced cytotoxic immune response as one of the mechanisms. In our laboratory, it has been confirmed an enhancement of natural killer activity in mice irradiated with whole-body 0.5Gy gamma-rays. Metastasis is accomplished by multistep process, involving basement membrane destruction, local invasion, intravasation, survival in the bloodstream, extravasation into distant organs, and proliferation at the target site. Besides, a lot of growth factors and proteases are involved in these steps. As to mechanism of inhibition of tumor metastasis induced by low-dose whole-body irradiation, studies from the standpoint of tumor invasion have not been reported. Here, inhibitory effect of 0.5Gy whole-body gamma-ray irradiation on tumor metastasis and its mechanism were examined in pulmonary metastasis model mice injected with B16 melanoma cells. Consequently, 0.5Gy whole-body gamma ray irradiation significantly suppressed colony formation in the lungs. Expression of matrix metalloproteinase- 2 (MMP- 2), a proteinase related to metastasis, in lung tissues was suppressed by the radiation. Alteration of tissue inhibitor of matrix metalloproteinase (TIMP) after the gamma-ray irradiation was examined. Expression of TIMP-1 and TIMP-2 mRNA in the lungs were significantly increased. In order to clarify the inhibitory effect obtained in the in vivo metastatic lung cancer model mice, we studied effects of gamma-rays on cell proliferation, alterations of mRNA and proteins related to tumor metastasis in cultured B16 melanoma cells. Proliferation of B16 melanoma cells was decreased in a dose-dependent manner. MMP-2 mRNA expression was not altered in any doses of gamma-rays. Thought expression of the protein was slightly

Fractionated total body irradiation and autologous bone marrow transplantation in dogs: Hemopoietic recovery after various marrow cell doses

International Nuclear Information System (INIS)

Bodenburger, U.; Kolb, H.J.; Thierfelder, S.; Netzel, B.; Schaeffer, E.; Kolb, H.

1980-01-01

Hemopoietic recovery was studied in dogs given 2400 R fractionated total body irradiation within one week and graded doses of cryopreserved autologous bone marrow. Complete hemopoietic recovery including histology was observed after this dose and sufficient doses of marrow cells. Doses of more than 5.5 x 10 7 mononuclear marrow cells/kg body weight were sufficient for complete recovery in all dogs, 1.5 to 5.5 x 10 7 cells/kg were effective in some of the dogs and less than 1.5 x 10 7 cells/kg were insufficient for complete recovery. Similarly, more than 30000 CFUsub(c)/kg body weight were required for hemopoietic recovery. The optimal marrow cell dose which has been defined as the minimal dose required for the earliest possible recovery of leukocyte and platelet counts was 7-8 x 10 7 mononuclear marrow cells/kg body weight. It has been concluded that fractionated total body irradiation with 2400 R dose not require greater doses of marrow cells for hemopoietic reconstitution than lower single doses and that the hemopoietic microenvironment is not persistently disturbed after this dose. (author)

Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model

DEFF Research Database (Denmark)

Jespersen, Henrik; Lindberg, Mattias F; Donia, Marco

2017-01-01

Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 - a melanoma PDX model where tumor cells and tumor...

Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms’ Tumor: A CIBMTR retrospective analysis

Science.gov (United States)

Malogolowkin, Marcio H.; Hemmer, Michael T.; Le-Rademacher, Jennifer; Hale, Gregory A; Metha, Parinda A.; Smith, Angela R.; Kitko, Carrie; Abraham, Allistair; Abdel-Azim, Hisham; Dandoy, Christopher; Diaz, Miguel Angel; Gale, Robert Peter; Guilcher, Greg; Hayashi, Robert; Jodele, Sonata; Kasow, Kimberly A.; MacMillian, Margaret L.; Thakar, Monica; Wirk, Baldeep M.; Woolfrey, Ann; Thiel, E L

2017-01-01

Despite the dramatic improvement in the overall survival for patients diagnosed with Wilms’ tumor (WT), the outcomes for those that experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR). The 5-year estimates for event free survival (EFS) and overall survival (OS) were 36% (95% CI; 29 – 43%) and 45% (95% CI; 38 – 51%) respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality (TRM) showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. Since attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus high-dose chemotherapy followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. Since disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy. PMID:28869618

Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

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Song, Chang W., E-mail: songx001@umn.edu [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yoon-Jin [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Park, Inhwan [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Koonce, Nathan A. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hui, Susanta [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Kim, Mi-Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Dusenbery, Kathryn E. [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Sperduto, Paul W. [Minneapolis Radiation Oncology and Gamma Knife Center, University of Minnesota, Minneapolis, Minnesota (United States); Cho, L. Chinsoo [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States)

2015-09-01

Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo–in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.

Chloroquine Engages the Immune System to Eradicate Irradiated Breast Tumors in Mice

International Nuclear Information System (INIS)

Ratikan, Josephine Anna; Sayre, James William; Schaue, Dörthe

2013-01-01

Purpose: This study used chloroquine to direct radiation-induced tumor cell death pathways to harness the antitumor activity of the immune system. Methods and Materials: Chloroquine given immediately after tumor irradiation increased the cure rate of MCaK breast cancer in C3H mice. Chloroquine blocked radiation-induced autophagy and drove MCaK cells into a more rapid apoptotic and more immunogenic form of cell death. Results: Chloroquine treatment made irradiated tumor vaccines superior at inducing strong interferon gamma-associated immune responses in vivo and protecting mice from further tumor challenge. In vitro, chloroquine slowed antigen uptake and degradation by dendritic cells, although T-cell stimulation was unaffected. Conclusions: This study illustrates a novel approach to improve the efficacy of breast cancer radiation therapy by blocking endosomal pathways, which enhances radiation-induced cell death within the field and drives antitumor immunity to assist therapeutic cure. The study illuminates and merges seemingly disparate concepts regarding the importance of autophagy in cancer therapy

Ocular complication with therapeutic irradiation of malignant tumor in the maxilla

International Nuclear Information System (INIS)

Takahashi, Hisashi; Konno, Akiyoshi

1983-01-01

This paper describes the ocular complications of 33 cases who had undergone therapeutic irradiation for malignant tumor in the maxilla. Irradiation was performed with megavoltage x-ray of 6000 rads or more. Among the 18 patients with intraorbital infiltration of the tumor, 8 showed severe ocular lesion. In contrast, only 3 among the 15 patients without intraorbital infiltration showed severe lesions. Retinopathy was observed in 13 patients. Funduscopic findings and fluorescein angiograms were similar to those in diabetic retinopathy. One case of retinopathy with neovascular change was treated with panretinal argon laser photocoagulation; however, it was not successful. Most of the 7 glaucoma patients had neovascular glaucoma. They had the worst prognosis. (author)

Preliminary studies on factors controlling the rate of regrowth of heavily x-irradiated rat rhabdomyosarcoma tumors

International Nuclear Information System (INIS)

Tenforde, T.S.; Curtis, S.B.; Woodruff, H.K.; Parks, D.L.; Daniels, S.J.; Crabtree, K.E.; Schilling, W.A.; DeGuzman, R.J.

1977-12-01

Following large single doses of x rays, rat rhabdomyosarcoma tumors exhibit a volume response which characteristically has a swelling phase, a regression phase, a rapid ''initial'' regrowth phase and a slow ''late'' regrowth phase. The preliminary experiments reported here were designed to examine three mechanisms that may underlie the reduction in growth rate occurring in the late regrowth phase; heritable non-lethal cellular damage, host immunity, delayed post-irradiation tissue and vascular damage. Based on retransplantation experiments and studies with immunosuppressed rats, neither heritable non-lethal damage nor host immune factors appear to influence the regrowth rate of tumors receiving radiation doses well below the cure level. After an x-ray dose approaching the cure level, regrowing tumors were observed to have a greatly reduced growth rate, possibly reflecting the presence of heritable non-lethal damage and/or an increased antigenicity of the heavily irradiated tumor cells. Morphometric analysis of histological sections did not reveal statistically significant abnormalities at the cellular level during the late regrowth phase, except for an increase in the percentage of necrotic tissue relative to non-irradiated tumors. The morphological resolution of small blood vessels was not adequate to evaluate delayed vascular damage in regrowing irradiated tumors

Dose-escalated total body irradiation and autologous stem cell transplantation for refractory hematologic malignancy

International Nuclear Information System (INIS)

McAfee, Steven L.; Powell, Simon N.; Colby, Christine; Spitzer, Thomas R.

2002-01-01

Purpose: To evaluate the feasibility of dose escalation of total body irradiation (TBI) above the previously reported maximally tolerated dose, we have undertaken a Phase I-II trial of dose-escalated TBI with autologous peripheral blood stem cell transplantation (PBSCT) for chemotherapy-refractory lymphoma. Methods and Materials: Nine lymphoma patients with primary refractory disease (PRD) or in resistant relapse (RR) received dose-escalated TBI and PBSCT. The three dose levels of fractionated TBI (200 cGy twice daily) were 1,600 cGy, 1,800 cGy, and 2,000 cGy. Lung blocks were used to reduce the TBI transmission dose by 50%, and the chest wall dose was supplemented to the prescribed dose using electrons. Shielding of the kidneys was performed to keep the maximal renal dose at 1,600 cGy. Three patients, two with non-Hodgkin's lymphoma (NHL) in RR and one with PRD Hodgkin's disease, received 1,600 cGy + PBSCT, three patients (two NHL in RR, one PRD) received 1,800 cGy + PBSCT, and three patients with NHL (two in RR, one PRD) received 2,000 cGy + PBSCT. Results: Toxicities associated with this high-dose TBI regimen included reversible hepatic veno-occlusive disease in 1 patient, Grade 2 mucositis requiring narcotic analgesics in 8 patients, and neurologic toxicities consisting of a symmetrical sensory neuropathy (n=4) and Lhermitte's syndrome (n=1). Interstitial pneumonitis developed in 1 patient who received 1,800 cGy after receiving recombinant α-interferon (with exacerbation after rechallenge with interferon). Six (66%) patients achieved a response. Four (44%) patients achieved complete responses, three of which were of a duration greater than 1 year, and 2 (22%) patients achieved a partial response. One patient remains disease-free more than 5 years posttransplant. Corticosteroid-induced gastritis and postoperative infection resulted in the death of 1 patient in complete response, 429 days posttransplant. Conclusion: TBI in a dose range 1,600-2,000 cGy as

Glycolysis-related gene induction and ATP reduction during fractionated irradiation. Markers for radiation responsiveness of human tumor xenografts

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Goetze, K.; Meyer, S.S.; Mueller-Klieser, W. [University Medical Center Mainz Univ. (Germany). Inst. of Physiology and Pathophysiology; Yaromina, A. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Zips, D. [University Hospital Tuebingen (Germany). Dept. of Radiation Oncology; Baumann, M. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Dresden Technical Univ. Dresden (Germany). Dept. of Radiation Oncology

2013-09-15

Background and purpose: Lactate was previously shown to be a prognostic but not a predictive pre-therapeutic marker for radiation response of tumor xenografts. We hypothesize that metabolic changes during fractionated irradiation may restrict the predictiveness of lactate regarding tumor radiosensitivity. Materials and methods: Tumor xenografts were generated in nude mice by implanting 4 head and neck squamous cell carcinoma lines with different sensitivities to fractionated irradiation. Tumors were irradiated with up to 15 fractions of 2 Gy over a period of 3 weeks, and ATP and lactate levels were measured in vital tumor areas with induced metabolic bioluminescence imaging. Corresponding changes in mRNA expression of glycolysis-related genes were determined by quantitative RT-PCR. Results: Lactate content decreased significantly in 3 out of 4 cell lines in the course of irradiation showing no correlation with cell line-specific radiosensitivity. Radiation-induced changes in ATP levels and glycolysis-related mRNA expression, however, only occurred in radiosensitive or intermediately radioresistant xenografts, whereas these parameters remained unchanged in radioresistant tumors. Conclusion: Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment. (orig.)

Sensorineural hearing loss following irradiation to the malignant tumor of the head and neck

International Nuclear Information System (INIS)

Murakami, Masafumi; Kobari, Hitomi; Kanno, Hidetaka; Aikawa, Tohru; Anzai, Tomohiro; Okamura, Hiro-oki; Ohtani, Iwao; Hoshino, Toshiaki

1989-01-01

We observed sensorineural hearing loss following X-ray irradiation to the malignant tumor of head and neck. There were 24 patients whose auditory organs lied within the irradiation field. Ten of these patients were affected by sensorineural hearing loss. Hearing loss occurred at a high frequency in elderly patients, epipharynx tumor and high dose of irradiation. Many cases revealed high tone hearing loss. Most cases showed about a 20∼30 dB hearing loss, so their impediment seemed not severe in daily life. In some of these cases, we could have temporal bone findings, but there were no particular findings relevant to sensorineural hearing loss. (author)

Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity

Directory of Open Access Journals (Sweden)

Cerkovnik Petra

2010-09-01

Full Text Available Abstract Background An ideal tumor vaccine should activate both effector and memory immune response against tumor-specific antigens. Beside the CD8+ T cells that play a central role in the generation of a protective immune response and of long-term memory, dendritic cells (DCs are important for the induction, coordination and regulation of the adaptive immune response. The DCs can conduct all of the elements of the immune orchestra and are therefore a fundamental target and tool for vaccination. The present study was aimed at assessing the ability of tumor vaccine composed of C-class CpG ODNs and irradiated melanoma tumor cells B16F1 followed by two additional injections of CpG ODNs to induce the generation of a functional long-term memory response in experimental tumor model in mice (i.p. B16F1. Results It has been shown that the functional memory response in vaccinated mice persists for at least 60 days after the last vaccination. Repeated vaccination also improves the survival of experimental animals compared to single vaccination, whereas the proportion of animals totally protected from the development of aggressive i.p. B16F1 tumors after vaccination repeated three times varies between 88.9%-100.0%. Additionally, the long-term immune memory and tumor protection is maintained over a prolonged period of time of at least 8 months. Finally, it has been demonstrated that following the vaccination the tumor-specific memory cells predominantly reside in bone marrow and peritoneal tissue and are in a more active state than their splenic counterparts. Conclusions In this study we demonstrated that tumor vaccine composed of C-class CpG ODNs and irradiated tumor cells followed by two additional injections of CpG ODNs induces a long-term immunity against aggressive B16F1 tumors.

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

International Nuclear Information System (INIS)

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

1982-01-01

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

Effects of whole-body irradiation on neonatally thymectomized mice. Incidence of benign and malignant tumors

International Nuclear Information System (INIS)

Anderson, R.E.; Howarth, J.L.; Troup, G.M.

1978-01-01

The individual and combined effects of neonatal thymectomy and whole-body irradiation on the prevalence of benign and malignant tumors in germ-free female mice of the Charles Rivers line were studied to determine if a portion of the tumorigenic effects of irradiation can be attributed to injury of the thymic-dependent component of the immune response. Neonatal thymectomy increased (a) the incidence of benign and malignant tumors and (b) the prevalence of multiple primary neoplasms in an individual mouse. Whole-body exposure to 700 rad at 6 weeks of age further increased the incidence of tumors, but the relative magnitude of this increase was less pronounced than in sham-operated controls. Thus, the cumulative effects of thymectomy plus irradiation are less pronounced than the sum of the individual effects. One of several possible explanations for this observation is that a portion of the carcinogenic effects of whole-body irradiation is mediated by suppression of the thymic-dependent component of the immune response

Feasibility of carbon-ion radiotherapy for re-irradiation of locoregionally recurrent, metastatic, or secondary lung tumors.

Science.gov (United States)

Hayashi, Kazuhiko; Yamamoto, Naoyoshi; Karube, Masataka; Nakajima, Mio; Tsuji, Hiroshi; Ogawa, Kazuhiko; Kamada, Tadashi

2018-03-02

Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon-ion radiotherapy who were treated with re-irradiation with carbon-ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy-three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon-ion radiotherapy was 52.8 Gy (relative biological effectiveness) and the median dose of re-irradiation was 66.0 Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 18 months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2-year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re-irradiation with carbon-ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re-irradiation with carbon-ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Effect of focal irradiation on plasma kallikrein activity in tumor bearing rats

International Nuclear Information System (INIS)

Makoyo, P.O.Z.R.; West, W.L.

1977-01-01

The activated plasma kallikrein from tumor bearing rats before and after focal irradiation of the hind limbs was measured by the hydrolysis of 0.015M N-(p-toluene sulfonyl)-L arginine methyl ester (TAME). Blood was collected from abdominal aorta of rats anesthetized with diethyl ether into plastic tubes containing 1 volume of 3.8 percent sodium citrate for each 9 volumes. Plasma was isolated by centrifugation (2000 g) at 4 0 C. Small pieces of minced tumor tissue were inserted in a trochar and inoculated in the hind limbs of the rats. Morris hepatomas 7777 and 3924A were transplanted subcutaneously over the hind legs while Walker 256 tumor was transplanted intramuscularly in the hind limbs. Plasma kallikrein (μm TAME utilized/ml/hr) was decreased in three different groups of tumor bearing rats: Walker tumor from 207 +- 34 to 114 +- 30 Hepatoma 7777 from 219 +- 13 to 106 +- 3 and Hepatoma 3924A from 227 +- 7 to 133 +- 5. Two hours after focal irradiation (1000 R) plasma kallikrein decreased further in Walker tumor and hepatoma 7777 to 55 +- 5 and 96 +- 3.6 respectively. The plasma of tumor bearing rats becomes deficient in kallikrein at about the time metastases may be identified. The acute fall in plasma kallikrein is consistent with the overall stress mechanism

Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: evidence for autoreactive T-cell dysfunction not correlated with phenotype, karyotype, or clinical status

International Nuclear Information System (INIS)

Han, T.; Bloom, M.L.; Dadey, B.; Bennett, G.; Minowada, J.; Sandberg, A.A.; Ozer, H.

1982-01-01

In the present study, there was a complete lack of autologous MLR between responding T cells or T subsets and unirradiated or irradiated leukemic B cells or monocytes in all 20 patients with CLL, regardless of disease status, stage, phenotype, or karyotype of the disease. The stimulating capacity of unirradiated CLL B cells and CLL monocytes or irradiated CLL B cells was significantly depressed as compared to that of respective normal B cells and monocytes in allogeneic MLR. The responding capacity of CLL T cells was also variably lower than that of normal T cells against unirradiated or irradiated normal allogeneic B cells and monocytes. The depressed allogeneic MLR between CLL B cells or CLL monocytes and normal T cells described in the present study could be explained on the basis of a defect in the stimulating antigens of leukemic B cells or monocytes. The decreased allogeneic MLR of CLL T cells might simply be explained by a defect in the responsiveness of T lymphocytes from patients with CLL. However, these speculations do not adequately explain the complete lack of autologous MLR in these patients. When irradiated CLL B cells or irradiated CLL T cells were cocultured with normal T cells and irradiated normal B cells, it was found that there was no suppressor cell activity of CLL B cells or CLL T cells on normal autologous MLR. Our data suggest that the absence or dysfunction of autoreactive T cells within the Tnon-gamma subset account for the lack of autologous MLR in patients with CLL. The possible significance of the autologous MLR, its relationship to in vivo immunoregulatory mechanisms, and the possible role of breakdown of autoimmunoregulation in the oncogenic process of certain lymphoproliferative and autoimmune diseases in man are discussed

Cell kinetics of irradiated experimental tumors: cell transition from the non-proliferating to the proliferating pool

International Nuclear Information System (INIS)

Potmesil, M.; Goldfeder, A.

1980-01-01

In murine mammary carcinomas, parenchymal tumor cells with dense nucleoli traverse the cell cycle and divide, thus constituting the proliferating pool. Cells with trabeculate or ring-shaped nucleoli either proceed slowly through G 1 phase or are arrested in it. The role of these non-proliferating, G 1 phase-confined cells in tumor regeneration was studied in vivo after a subcurative dose of X-irradiation in two transplantable tumor lines. Tumor-bearing mice were continuously injected with methyl[ 3 H]thymidine before and after irradiation. Finally, the labeling was discontinued, mice injected with vincristine sulfate and cells arrested in metaphase were accumulated over 10-hrs. Two clearly delineated groups of vincristine-arrested mitoses emerged in autoradiograms prepared from tumor tissue at the time of starting tumor regrowth: one group with the silver-grain counts corresponding to the background level, the other with heavily labeled mitoses. As the only source of unlabeled mitoses was unlabeled G 1 phase-confined cells persisting in the tumor, this indicated cell transition from the non-proliferating to the proliferating pool, which took place in the initial phase of the tumor regrowth. Unlabeled progenitors have apparently remained in G 1 phase for at least 5-12 days after irradiation. (author)

Tumor-associated proteins in rat submandibular gland induced by DMBA and irradiation

International Nuclear Information System (INIS)

Oh, Sung Ook; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

1997-01-01

This study was performed in order to identify changes of the plasma membrane proteins in rat submandibular gland tumors induced by 7,12-dimethylbenz[a]anthracene [DMBA] and X-irradiation. Two kinds of tumor associated membrane proteins (protein A and B) were isolated with 3 M KCl extraction from rat submandibular gland tumors induced by DMBA and X-irradiation. To identify their antigenicities, immunoelectrophoresis and double immunodiffusion was carried out with various proteins extracted from liver, heart, skin and pancreas of adult rats and from embryonic liver, heart and skin. The rabbit antisera against the protein A did not cross-react with any of the proteins extracted from the above mentioned tissues, suggesting that protein A might be tumor specific antigen. However, the rabbit antisera against protein B was precipitated with proteins extracted from the liver of adult and embryonic rats. Polyacrylamide gel electrophoresis of these two proteins (A and B) showed that protein A was a dimer with molecular weights of 69,000 and 35,000 dalton, whereas protein B was a monomer with molecular weight of 50,000 dalton.

In vitro and in vivo studies on the cytotoxicity of irradiated silk fibroin against mouse melanoma tumor cell

International Nuclear Information System (INIS)

Byun, Eui-Baek; Sung, Nak-Yun; Kwon, Sun-Kyu; Song, Beom-Seok; Kim, Jae-Hun; Choi, Jong-il; Hwang, Han-Joon; Byun, Myung-Woo; Lee, Ju-Woon

2009-01-01

The physicochemical properties of proteins can be altered by irradiation. But, it is rarely that the researches on the functional properties of irradiated proteins have been reported. Fibroin is a fibrous protein derived from silkworm Bombyx mori and has been suggested as a biomaterial for biomedical application. Therefore, fibroin was selected as a model protein and was examined with the irradiation effects on the cytotoxicity of fibroin on tumor cell. The cytotoxicity of fibroin against mouse melanoma cell (B16BL6) showed a significant increase dependent upon the increase of irradiation dose. And also, the splenocyte proliferation activities of fibroin were increased by gamma irradiation. In addition, the oral administration of irradiated fibroin significantly increased the inhibition rate of tumor growth in tumor-bearing mouse model. The reason might be due to the change of protein structure by gamma irradiation and is being studied. From these result, it could be concluded that the irradiated fibroin might be a potential candidate as a valuable product in food and medical industry.

In vitro and in vivo studies on the cytotoxicity of irradiated silk fibroin against mouse melanoma tumor cell

Energy Technology Data Exchange (ETDEWEB)

Byun, Eui-Baek [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Division of Bioresources and Biosciences, Faculty of Agriculture, Graduate school of Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581 (Japan); Sung, Nak-Yun [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kwon, Sun-Kyu [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Graduate school of Food and Biotechnology, Korea University, Jochiwon 339-800 (Korea, Republic of); Song, Beom-Seok; Kim, Jae-Hun; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Hwang, Han-Joon [Graduate school of Food and Biotechnology, Korea University, Jochiwon 339-800 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

2009-07-15

The physicochemical properties of proteins can be altered by irradiation. But, it is rarely that the researches on the functional properties of irradiated proteins have been reported. Fibroin is a fibrous protein derived from silkworm Bombyx mori and has been suggested as a biomaterial for biomedical application. Therefore, fibroin was selected as a model protein and was examined with the irradiation effects on the cytotoxicity of fibroin on tumor cell. The cytotoxicity of fibroin against mouse melanoma cell (B16BL6) showed a significant increase dependent upon the increase of irradiation dose. And also, the splenocyte proliferation activities of fibroin were increased by gamma irradiation. In addition, the oral administration of irradiated fibroin significantly increased the inhibition rate of tumor growth in tumor-bearing mouse model. The reason might be due to the change of protein structure by gamma irradiation and is being studied. From these result, it could be concluded that the irradiated fibroin might be a potential candidate as a valuable product in food and medical industry.

Autologous Chondrocyte Implantation in Osteoarthritic Surroundings

DEFF Research Database (Denmark)

Ossendorff, Robert; Grad, Sibylle; Stoddart, Martin J

2018-01-01

BACKGROUND: Autologous chondrocyte implantation (ACI) fails in up to 20% of cases. Advanced intra-articular degeneration paired with an inflammatory environment may be closely related to implantation failure. Certain cytokines have been identified to play a major role during early osteoarthritis....... PURPOSE: To investigate the effects of tumor necrosis factor α (TNFα) and its potential inhibition by adalimumab on cartilage regeneration in an in vitro model of ACI. STUDY DESIGN: Controlled laboratory study. METHODS: Bovine articular chondrocytes were cultivated and transferred at passage 3 to fibrin...

Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours

NARCIS (Netherlands)

van den Berkmortel, F.; Gidding, C.; de Kanter, M.; Punt, C. J. A.

2006-01-01

Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The

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

International Nuclear Information System (INIS)

Imanaka, Kazufumi; Tanaka, Koji; Sasai, Keisuke

1984-01-01

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

Immuno-enhancement in tumor-bearing mice induced by whole body X-irradiation with 75 mGy

International Nuclear Information System (INIS)

Zhang Ying; Li Xiuyi; Gong Shouliang; Liu Shuzheng

2000-01-01

Objective: In present study the authors observed the effect of whole body irradiation (WBI) with 75 mGy X-rays on the immune function of tumor-bearing mice. Methods: Lewis lung carcinoma cells were implanted into the right thigh muscle of C57BL/6J mice. Ten days after tumor implantation, the tumor-bearing mice were administrated with 75 mGy X-rays WBI, then the mice were sacrificed 18 h after irradiation to detect the immune parameters including the spontaneous proliferation of thymocytes, the proliferative response of splenocytes to ConA and LPS, the cytotoxic activities of specific cytotoxic lymphocytes (CTL) and natural killer cells (NK), as well as lymphokine activated killer cells (LAK) in spleen. The methods the authors used were 3 H-TdR incorporation or release assay. Results: the immune parameters of exposed tumor-bearing mice were much higher than those of sham-irradiated tumor-bearing mice (P<0.01). Conclusion: These results suggested that low dose radiation (LDR) could enhance the immune function of tumor-bearing mice, which might be of practical significance in the prevention and therapy of cancer

Evaluation of a combination tumor treatment using thermo-triggered liposomal drug delivery and carbon ion irradiation.

Science.gov (United States)

Kokuryo, Daisuke; Aoki, Ichio; Yuba, Eiji; Kono, Kenji; Aoshima, Sadahito; Kershaw, Jeff; Saga, Tsuneo

2017-07-01

The combination of radiotherapy with chemotherapy is one of the most promising strategies for cancer treatment. Here, a novel combination strategy utilizing carbon ion irradiation as a high-linear energy transfer (LET) radiotherapy and a thermo-triggered nanodevice is proposed, and drug accumulation in the tumor and treatment effects are evaluated using magnetic resonance imaging relaxometry and immunohistology (Ki-67, n = 15). The thermo-triggered liposomal anticancer nanodevice was administered into colon-26 tumor-grafted mice, and drug accumulation and efficacy was compared for 6 groups (n = 32) that received or did not receive the radiotherapy and thermo trigger. In vivo quantitative R 1 maps visually demonstrated that the multimodal thermosensitive polymer-modified liposomes (MTPLs) can accumulate in the tumor tissue regardless of whether the region was irradiated by carbon ions or not. The tumor volume after combination treatment with carbon ion irradiation and MTPLs with thermo-triggering was significantly smaller than all the control groups at 8 days after treatment. The proposed strategy of combining high-LET irradiation and the nanodevice provides an effective approach for minimally invasive cancer treatment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Re-irradiation for metastatic brain tumors with whole-brain radiotherapy

International Nuclear Information System (INIS)

Akiba, Takeshi; Kunieda, Etsuo; Kogawa, Asuka; Komatsu, Tetsuya; Tamai, Yoshifumi; Ohizumi, Yukio

2012-01-01

The objective of this study was to determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P=0.003) and the Karnofsky performance status at the time of re-irradiation (P=0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P=0.050). Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high. (author)

Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

Science.gov (United States)

Kuranishi, Fumito; Ohno, Tadao

2013-06-04

Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.

Science.gov (United States)

Niess, Hanno; von Einem, Jobst C; Thomas, Michael N; Michl, Marlies; Angele, Martin K; Huss, Ralf; Günther, Christine; Nelson, Peter J; Bruns, Christiane J; Heinemann, Volker

2015-04-08

Adenocarcinoma originating from the digestive system is a major contributor to cancer-related deaths worldwide. Tumor recurrence, advanced local growth and metastasis are key factors that frequently prevent these tumors from curative surgical treatment. Preclinical research has demonstrated that the dependency of these tumors on supporting mesenchymal stroma results in susceptibility to cell-based therapies targeting this stroma. TREAT-ME1 is a prospective, uncontrolled, single-arm phase I/II study assessing the safety and efficacy of genetically modified autologous mesenchymal stromal cells (MSC) as delivery vehicles for a cell-based gene therapy for advanced, recurrent or metastatic gastrointestinal or hepatopancreatobiliary adenocarcinoma. Autologous bone marrow will be drawn from each eligible patient after consent for bone marrow donation has been obtained (under a separate EC-approved protocol). In the following ~10 weeks the investigational medicinal product (IMP) is developed for each patient. To this end, the patient's MSCs are stably transfected with a gamma-retroviral, replication-incompetent and self-inactivating (SIN) vector system containing a therapeutic promoter - gene construct that allows for tumor-specific expression of the therapeutic gene. After release of the IMP the patients are enrolled after given informed consent for participation in the TREAT-ME 1 trial. In the phase I part of the study, the safety of the IMP is tested in six patients by three treatment cycles consisting of re-transfusion of MSCs at different concentrations followed by administration of the prodrug Ganciclovir. In the phase II part of the study, sixteen patients will be enrolled receiving IMP treatment. A subgroup of patients that qualifies for surgery will be treated preoperatively with the IMP to verify homing of the MSCs to tumors as to be confirmed in the surgical specimen. The TREAT-ME1 clinical study involves a highly innovative therapeutic strategy combining cell

Autologous Fat Grafting Reduces Pain in Irradiated Breast: A Review of Our Experience

Directory of Open Access Journals (Sweden)

Fabio Caviggioli

2016-01-01

Full Text Available Introduction. Pain syndromes affect women after conservative and radical breast oncological procedures. Radiation therapy influences their development. We report autologous fat grafting therapeutical role in treating chronic pain in irradiated patients. Materials and Methods. From February 2006 to November 2014, we collect a total of 209 patients who meet the definition of “Postmastectomy Pain Syndrome” (PMPS and had undergone mastectomy with axillary dissection (113 patients or quadrantectomy (96 patients. Both procedures were followed by radiotherapy. We performed fat grafting following Coleman’s procedure. Mean amount of adipose tissue injected was 52 cc (±8.9 cc per breast. Seventy-eight in 209 patients were not treated surgically and were considered as control group. Data were gathered through preoperative and postoperative VAS questionnaires; analgesic drug intake was recorded. Results. The follow-up was at 12 months (range 11.7–13.5 months. In 120 treated patients we detected pain decrease (mean ± SD point reduction, 3.19 ± 2.86. Forty-eight in 59 patients stopped their analgesic drug therapy. Controls reported a mean ± SD decrease of pain of 1.14 ± 2.72. Results showed that pain decreased significantly in patients treated (p<0.005, Wilcoxon rank-sum test. Conclusion. Our 8-year experience confirms fat grafting effectiveness in decreasing neuropathic pain.

Effects of X-irradiation on membranes of tumor cells

International Nuclear Information System (INIS)

Fonck, K.

1982-01-01

The aim of the investigation was to gain more insight into the effect of ionizing radiation on biomembranes, especially the membrane phospholipids. A general outline of the experimental approach is given in the first chapter. The influence of membrane-active agents and hyperthermia on cell survival after irradiation was studied. Phospholipid turnover was followed by measuring the incorporation of radioactive precursors. The second chapter is an introduction to general radiobiology and to phospholipid metabolism. After the presentation of some physico-chemical properties of ionizing radiation, the effects on cells and cellular components are described. In chapters 3 to 6 the experimental part is described. Chapter 3 starts with the determination of the cellular survival of L5178Y lymphoma cells after X-irradiation. In chapter 4 the lipid composition of lymphosarcoma cell nuclei is presented and in chapter 5 studies on the effect of X-irradiation on the incorporation of palmitate and arachidonate into the phospholipids of lymphosarcoma cells are described. Chapter 6 describes experiments in which lymphosarcoma cells isolated from the spleens of tumor-bearing mice were used to study the effect of a low dose of X-rays (5 Gy) on the incorporation of [ 3 H]palmitate and [ 14 C]arachidonate into the lipids of the tumor cells. These fatty acids were rapidly incorporated especially into the phospholipids of the cells. Chapter 7 contains a general discussion on the experimental results. (Auth.)

Radiosensitizing effect of nitric oxide in tumor cells and experimental tumors irradiated with gamma rays and proton beams; Efecto radiosensibilizador del oxido nitrico en celulas tumorales y en tumores experimentales irradiados con radiacion gamma y con haces de protones

Energy Technology Data Exchange (ETDEWEB)

Policastro, Lucia L; Duran, Hebe; Molinari, Beatriz L [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Radiobiologia; Schuff, Juan A; Kreiner, Andres J; Burlon, Alejandro A; Debray, Mario E; Kesque, Jose M; Ozafran, Mabel J; Vazquez, Monica E [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Fisica; Davidson, Jorge; Davidson, Miguel [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires (Argentina); Somacal, Hector R; Valda, Alejandro A [Universidad Nacional de General San Martin , Villa Ballester (Argentina). Escuela de Ciencia y Tecnologia

2003-07-01

Nitric oxide (NO) has been reported to be a radiosensitizer of mammalian cells under hypoxic conditions. In a previous study, we demonstrated an enhancement in radiation response induced by NO in mouse tumor cells under aerobic conditions, with an increasing effect as a function of malignancy. The aim of the present study was to evaluate the effect of NO in tumor cells and in experimental tumors irradiated with {gamma} rays and proton beams. Irradiations were performed with a {sup 137}Cs {gamma} source and with proton beams generated by the TANDAR accelerator. Tumor cells were treated with the NO donor DETA-NO and the sensitizer enhancement ratio (SER) was calculated using the {alpha} parameter of the survival curve fitted to the linear-quadratic model. Tumor cells irradiated with protons were radio sensitized by DETA-NO only in the more malignant cells irradiated with low LET protons (2.69{+-}0.08 keV/{mu}m). For higher LET protons there were no radiosensitizing effect. For human tumor cells pre-treated with DETA-NO and irradiated with {gamma} rays, a significantly greater effect was demonstrated in the malignant cells (MCF-7) as compared with the near normal cells (HBL-100). Moreover, a significant decrease in tumor growth was demonstrated in mice pre-treated with the NO donor spermine and irradiated with {gamma} rays and low LET protons as compared with mice irradiated without pre-treatment with the NO donor. In conclusion, we demonstrated a differential effect of NO as a radiosensitizer of malignant cells, both with {gamma} rays and low LET protons. This selectivity, coupled to the in vivo inhibition of tumor growth, is of great interest for the potential use of NO releasing agents in radiotherapy. (author)

Cross-immunity among allogeneic tumors of rats immunized with solid tumors

International Nuclear Information System (INIS)

Ogasawara, Masamichi

1979-01-01

Several experiments were done for the study of cross-immunity among allogeneic rat tumors by immunization using gamma-irradiated or non-irradiated solid tumors. Each group of rats which were immunized with gamma-irradiation solid tumor inocula from ascites tumor cell line of tetra-ploid Hirosaki sarcoma, Usubuchi sarcoma or AH 130, showed an apparent resistance against the intraperitoneal challenge with Hirosaki sarcoma. A similar resistance was demonstrated in the case of the challenge with Usubuchi sarcoma into rats immunized with non-irradiated methylcholanthrene (MCA)-induced tumors. In using solid MCA tumors as immunogen and Hirosaki sarcoma as challenge tumor, it was also demonstrated in 2 out of 3 groups immunized with non-irradiated tumors. In the experiment of trying to induce cross-immunity between 2 MCA tumors by immunization with irradiated solid tumor only, the inhibitory effect on the growth was observed in the early stage in the treated groups as compared with the control one. From the above results, it may be considered that the immunization with irradiated solid tumors fromas cites cell lines and non-irradiated solid MCA tumors induced strong cross-immunity in general, but that the immunization with only irradiated solid MCA tumors induced weak cross-immunity commonly. (author)

Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. II. Distribution and cellularity of the marrow in irradiated and transfused animals

International Nuclear Information System (INIS)

Calvo, W.; Fliedner, T.M.; Herbst, E.; Huegl, E.; Bruch, C.

1976-01-01

Dogs were given transfusions of cryopreserved autologous mononuclear blood leukocytes after 1200 roentgens (R) (midline dose) whole-body x-irradiation. Bone marrow repopulation was studied by means of histomorphological methods at days 9 and 10 after transfusion of an average of 3 x 10 9 , 7 x 10 9 , 13 x 10 9 , and 31 x 10 9 cells. The return of marrow cellularity to normal values was related to the number of cells transfused. With low cell doses (3 x 10 9 and 7 x 10 9 ), the marrow regeneration at 10 days was focal. There were groups of cells (colonies) showing either erythropoiesis, myelopoiesis, or megakaryocytopoiesis in the osteal niches of the trabecular bones. Frequently such niches were seen showing complete cellular recovery next to niches with complete aplasia. With higher cell doses, all niches showed hemopoietic regeneration, and the cellularity approached normal values. No hemopoietic regeneration was observed in those skeletal parts that do not show hemopoiesis, even under normal circumstances

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

Science.gov (United States)

Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

2010-01-01

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

Directory of Open Access Journals (Sweden)

Sadanori Akita

2010-01-01

Full Text Available Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.

The influence of whole body 60Co-irradiation on distribution of 67Ga in tumor-bearing mice

International Nuclear Information System (INIS)

Wakao, Hiromi; Shimura, Akira; Higashi, Tomomitsu

1981-01-01

Since the initial findings that 67 Ga has a preferential affinity for soft tissue tumors, in humans numerous suggestions have been advanced for the basic mechanism involved. The effects produced by whole-body X-irradiation on the excretion and tissue distribution of 67 Ga have been reported by Swartzendruber and others. Bradley and coworkers have shown that these irradiation effects were associated with an increase in serum iron. The present investigation was undertaken in order to study the relationships between the change in the serum iron concentration and 67 Ga accumulation in the tumor and soft tissues in mice bearing Ehrlich's ascites tumor. The following results were obtained. (1) The serum iron concentration was significantly decreased between 3 and 6 hours after 10 Gy (1,000 rad) dose of whole-body 60 Co-irradiation. Subsequently, the serum iron levels were slowly elevated. (2) The uptake of 67 Ga in the tumor and soft tissues was increased if the serum iron concentration was decreased by whole-body 60 Co-irradiation during the early phase. On the contrary, if the serum iron concentration was high, the uptake of 67 Ga in the tumor was decreased. (3) The excretion of 67 Ga from the body was delayed if the serum iron concentration was decreased by whole-body 60 Co-irradiation. However, if the serum iron concentration was high, the excretion of 67 Ga from the body significantly increased. (author)

Proton irradiation augments the reduction in tumor progression observed with advanced age

Data.gov (United States)

National Aeronautics and Space Administration — Proton irradiation is touted for its improved tumor targeting due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory have...

Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation

International Nuclear Information System (INIS)

Peppoloni, S.; Herberman, R.B.; Gorelik, E.

1985-01-01

This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated tum- (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth

Overview of Radiosensitivity of Human Tumor Cells to Low-Dose-Rate Irradiation

International Nuclear Information System (INIS)

Williams, Jerry R.; Zhang Yonggang; Zhou Haoming; Gridley, Daila S.; Koch, Cameron J.; Slater, James M.; Little, John B.

2008-01-01

Purpose: We compared clonogenic survival in 27 human tumor cell lines that vary in genotype after low-dose-rate (LDR) or high-dose rate (HDR) irradiation. We measured susceptibility to LDR-induced redistribution in the cell cycle in eight of these cell lines. Methods and Materials: We measured clonogenic survival after up to 96 hours of LDR (0.25 Gy/h) irradiation. We compared these with clonogenic survival after HDR irradiation (50 Gy/h). Using flow cytometry, we measured LDR-induced redistribution as a function of time during LDR irradiation in eight of these cell lines. Results: Coefficients that describe clonogenic survival after both LDR and HDR irradiation segregate into four radiosensitivity groups that associate with cell genotype: mutant (mut)ATM, wild-type TP53, mutTP53, and an unidentified gene in radioresistant glioma cells. The LDR and HDR radiosensitivity correlates at lower doses (∼2 Gy HDR, ∼6 Gy LDR), but not at higher doses (HDR > 4 Gy; LDR > 6 Gy). The rate of LDR-induced loss of clonogenic survival changes at approximately 24 hours; wild-type TP53 cells become more resistant and mutTP53 cells become more sensitive. Redistribution induced by LDR irradiation also changes at approximately 24 hours. Conclusions: Radiosensitivity of human tumor cells to both LDR and HDR irradiation is genotype dependent. Analysis of coefficients that describe cellular radiosensitivity segregates 27 cell lines into four statistically distinct groups, each associating with specific genotypes. Changes in cellular radiosensitivity and redistribution in the cell cycle are strongly time dependent. Our data establish a genotype-dependent time-dependent model that predicts clonogenic survival, explains the inverse dose-rate effect, and suggests possible clinical applications

Induction of mouse mammary tumor virus RNA in mammary tumors of BALB/c mice treated with urethane, x-irradiation, and hormones

International Nuclear Information System (INIS)

Michalides, R.; van Deemter, L.; Nusse, R.; Hageman, P.

1979-01-01

The involvement of mouse mammary tumor virus (MTV) in the development of mammary tumors of nonviral etiology in BALB/c mice was studied by measuring the levels of MTV RNA, MTV DNA, and MTV proteins in spontaneously arising and hormally, chemically, and/or physically induced mammary tumors of BALB/c females. The following results were obtained: (1) spontaneous mammary tumors contained very low levels of MTV RNA; 4 x 10 -6 % of the cytoplasmic RNA was MTV RNA. No MTV proteins could be demonstrated by using sensitive radioimmunoassays for MTV proteins p27 and gp52. (2) Mammary tumors induced by treatments with urethane or x-irradiation alone contained higher levels of MTV RNA; these tumors contained 3- and 19-fold more MTV RNA, respectively, compared with spontaneous mammary tumors. (3) Mammary tumors induced by combined treatment with urethane and x-irradiation expressed high levels of MTV RNA in the mammary tumors; a 1,724-fold increase in MTV RNA content compared with spontaneous mammary tumors was observed. However, very low levels of MTV proteins gp52 and p27 were detected, suggesting some kind of impairment at the translation of MTV RNA. MTV RNA was also induced by this treatment in mammary glands and spleens, but not in the livers of tumor-bearing animals. (4) BALB/c females continuously exposed to prolactin contained high levels of MTV RNA and MTV proteins in stimulated mammary glands and in the hormonally induced mammary tumors. These findings suggest that MTV is not responsible for the maintenance and probably also not for the development of all murine mammary cancers

Cell survival of human tumor cells compared with normal fibroblasts following 60Co gamma irradiation

International Nuclear Information System (INIS)

Lloyd, E.L.; Henning, C.B.; Reynolds, S.D.; Holmblad, G.L.; Trier, J.E.

1982-01-01

Three tumor cell lines, two of which were shown to be HeLa cells, were irradiated with 60 Co gamma irradiation, together with two cell cultures of normal human diploid fibroblasts. Cell survival was studied in three different experiments over a dose range of 2 to 14 gray. All the tumor cell lines showed a very wide shoulder in the dose response curves in contrast to the extremely narrow shoulder of the normal fibroblasts. In addition, the D/sub o/ values for the tumor cell lines were somewhat greater. These two characteristics of the dose response curves resulted in up to 2 orders of magnitude less sensitivity for cell inactivation of HeLa cells when compared with normal cells at high doses (10 gray). Because of these large differences, the extrapolation of results from the irradiation of HeLa cells concerning the mechanisms of normal cell killing should be interpreted with great caution

Intravesical instillation of Adriamycin plus irradiation in the prophylactic treatment of recurring bladder tumors

International Nuclear Information System (INIS)

Yoneda, Fumio; Kan, Masaharu; Tsujimura, Haruhiro; Nakajima, Mikio

1989-01-01

The prevention of the recurrence of bladder tumors was attempted in 45 patients by intravesical instillation of Adriamycin plus irradiation (20 Gy). 30 ml saline solution containing ADM 30mg was instilled into the bladder and then irradiation was performed every day for 10 days. Patients' ages ranged from 36 to 84 years with a mean of 66.5 years; the sex ratio was 3(M) : 1(F). The recurrence rate following therapy was 8.1% after 1 year, 29.4% after 2 years and 29.4% after 3 years. The recurrence rate was low in patients with low grade tumors, those with single tumors and those who received this combination therapy after surgery. Only one patient was obliged to interrupt the therapy due to a bladder irritation. (author)

Effects of hyperthermia, x-ray irradiation and their combination on ascites tumor cells of mice

International Nuclear Information System (INIS)

Kaneko, Itsuo

1982-01-01

Fibrosarcoma ascites tumor cells (PB8) from NMRI mice were used to investigate cell loss by hyperthermia and/or x-ray irradiation. The tumor cells were labelled by an injection of 125 I-deoxyuridine to the abdominal cavity of the donors 2 days before the physical treatments. The labelled cells, transfered in test tubes, were heated at 44 0 C for 10-20 min and/or irradiated by x-ray at 250-1612 rad, and were transplanted in the recipient abdominal cavity as soon as possible after the treatments. The radioactivity of the tumor cells, as an indicator of cell loss, was measured with a gamma spectrometer. In the irradiated group, the ratio of cell loss increased in a dose-dependent manner, starting from the 4th day after the transplantation to the 9th day. In the heated group, the ratio of cell loss increased in proportion to the heating time, starting without delay after transplantation. In the combination group, the effect of the treatments was more marked than that by each single treatment. In the early stage of this group, cell loss was by heating and then, from the 4th day, the irradiation effect mostly dominated. It is concluded from the above results that cell loss by heating or irradiation is independent and that the effect of the combination is additive. (author)

Radiation and host factors in human thyroid tumors following thymus irradiation

International Nuclear Information System (INIS)

Shore, R.E.; Pasternack, B.S.; Woodard, E.D.; Hempelmann, L.H.

1980-01-01

Thyroid tumor data from the 1971 survey of the Rochester, New York thymus irradiated population are further analyzed to study radiobiological and host factors. The analyses were based on the approx. 2650 irradiated subjects and 4800 sibling controls who had 5 or more years of follow-up. Twenty-four thyroid cancers and 52 thyroid adenomas were found in the irradiated group, and O thyroid cancers and 6 adenomas among the controls. The overall risk estimates were 3.8 thyroid cancers/10 6 persons/yr/rad and 4.5 thyroid adenomas/10 6 persons/yr/rad. The dose-response data (thyroid dose range of 5 to > 1000 rad) for thyroid cancer indicate both a linear and a dose-squared component, but no dose-squared component is evident for thyroid adenomas. At lower total doses (< 400 rad) there was a suggestion that dose fractionation diminished the thyroid cancer response, but a similar fractionation effect was not found for thyroid adenomas. The temporal pattern of tumors suggested an extended plateau of excess tumor production, rather than a wavelike temporal pattern. There was no evidence for an inverse relationship between thyroid radiation dose and thyroid cancer latency. Female and Jewish subjects had a higher risk of radiation-induced thyroid cancer than did their respective counterparts. The additive and multiplicative models of radiation effects were compared with respect to sex differences; neither model provided a superior fit to the data. The tentative nature of the conclusions is stressed because of the relatively small number of thyroid cancers. (author)

Cytotoxic effect of x-irradiation of mouse tumor cells in the presence of Korean ginseng extract

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Kwon, Hyoung Cheol; Kim, Jin Ki; Kim, Jung Soo [College of Medicine, Chonbuk National Univ., Junju (Korea, Republic of); Choi, Dong Seong [College of Medicine, Woosuck Univ., Wanju (Korea, Republic of)

2000-09-01

We already reported the results that aqueous extract of Korean ginseng roots showed a marked cytotoxicity. In this study, we investigated whether combined ginseng product with X-irradiation increase the cytotoxicity of tumor cells than X-irradiation or not. Fifty gram of Korean ginseng powder mixed with 1 L of distilled water was extracted with reflux flask under condition of 100 .deg. C for 5 hrs. This aqueous ginseng extract was filtered, centrifuged and then was freezed under condition of -90 .deg. C for 16-18 hrs. The freezing extract was dried with freeze drier, and then diluted. X-irradiation was given to tumor cells by 6 MeV linear accelerator. The cytotoxicity of ginseng in vitro was evaluated from its ability to reduce the clonogenecity of fibrosarcoma (FSa ll) cells. In X-irradiation alone group, each 2, 4, 6 and 8 Gy was given to tumor cells. In X-irradiation with ginseng group, 0.2 mg/mL or ginseng extract was exposed to tumor cells for 1 hour before X-irradiation. The yield for 50 g of ginseng extract which was treated with freezing drier was 3.13 g(6.3%). Cytotoxicity in vitro was measured as survival fraction which was judged from the curve, at ginseng concentration of 0.001, 0.01, 0.1 and 1 mg/ml were 0.89{+-}0.04, 0.86{+-}0.06, 0.73{+-}0.01 and 0.09{+-}0.02, respectively. Survival fraction at X-irradiation alone of 2, 4, 6 and 8 Gy were 0.81{+-}0.07, 0.42{+-}0.08, 0.15{+-}0.02, 0.03{+-}0.01, respectively. But, survival fraction in combined group of X-irradiation and ginseng (0.2mg/mL) at each same radiation dose were 0.28{+-}0.01, 0.18{+-}0.03, 0.08{+-}0.02, 0.006{+-}0.002, respectively (p<0.05). The yield for ginseng extract which was treated with freezing drier was 6.3%. Cytotoxicity of Fsa II in combined ginseng with X-irradiation group was increased than that at X-irradiation alone group, and its enhancing effect seemed to be added.

Cytotoxic effect of x-irradiation of mouse tumor cells in the presence of Korean ginseng extract

International Nuclear Information System (INIS)

Kwon, Hyoung Cheol; Kim, Jin Ki; Kim, Jung Soo; Choi, Dong Seong

2000-01-01

We already reported the results that aqueous extract of Korean ginseng roots showed a marked cytotoxicity. In this study, we investigated whether combined ginseng product with X-irradiation increase the cytotoxicity of tumor cells than X-irradiation or not. Fifty gram of Korean ginseng powder mixed with 1 L of distilled water was extracted with reflux flask under condition of 100 .deg. C for 5 hrs. This aqueous ginseng extract was filtered, centrifuged and then was freezed under condition of -90 .deg. C for 16-18 hrs. The freezing extract was dried with freeze drier, and then diluted. X-irradiation was given to tumor cells by 6 MeV linear accelerator. The cytotoxicity of ginseng in vitro was evaluated from its ability to reduce the clonogenecity of fibrosarcoma (FSa ll) cells. In X-irradiation alone group, each 2, 4, 6 and 8 Gy was given to tumor cells. In X-irradiation with ginseng group, 0.2 mg/mL or ginseng extract was exposed to tumor cells for 1 hour before X-irradiation. The yield for 50 g of ginseng extract which was treated with freezing drier was 3.13 g(6.3%). Cytotoxicity in vitro was measured as survival fraction which was judged from the curve, at ginseng concentration of 0.001, 0.01, 0.1 and 1 mg/ml were 0.89±0.04, 0.86±0.06, 0.73±0.01 and 0.09±0.02, respectively. Survival fraction at X-irradiation alone of 2, 4, 6 and 8 Gy were 0.81±0.07, 0.42±0.08, 0.15±0.02, 0.03±0.01, respectively. But, survival fraction in combined group of X-irradiation and ginseng (0.2mg/mL) at each same radiation dose were 0.28±0.01, 0.18±0.03, 0.08±0.02, 0.006±0.002, respectively (p<0.05). The yield for ginseng extract which was treated with freezing drier was 6.3%. Cytotoxicity of Fsa II in combined ginseng with X-irradiation group was increased than that at X-irradiation alone group, and its enhancing effect seemed to be added

Atypical teratoid/rhabdoid tumors: challenges and search for solutions

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Biswas, Ahitagni; Kashyap, Lakhan; Kakkar, Aanchal; Sarkar, Chitra; Julka, Pramod Kumar

2016-01-01

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central nervous system tumor commonly affecting children <3 years of age. It roughly constitutes 1%–2% of all pediatric central nervous system tumors. Recent data show that it is the most common malignant central nervous system tumor in children <6 months of age. Management of this aggressive tumor is associated with a myriad of diagnostic and therapeutic challenges. On the basis of radiology and histopathology alone, distinction of AT/RT from medulloblastoma or primitive neuroectodermal tumor is difficult, and hence this tumor has been commonly misdiagnosed as primitive neuroectodermal tumor for decades. Presence of a bulky heterogeneous solid-cystic mass with readily visible calcification and intratumor hemorrhage, occurring off-midline in children <3 years of age, should alert the radiologist toward the possibility of AT/RT. Presence of rhabdoid cells on histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal, and neuroectodermal markers along with loss of expression of SMARCB1/INI1 or SMARCA4/BRG1 help in establishing a diagnosis of AT/RT. The optimal management comprises maximal safe resection followed by radiation therapy and multiagent intensive systemic chemotherapy. Gross total excision is difficult to achieve in view of the large tumor size and location and young age at presentation. Leptomeningeal spread is noted in 15%–30% of patients, and hence craniospinal irradiation followed by boost to tumor bed is considered standard in children older than 3 years. However, in younger children, craniospinal irradiation may lead to long-term neurocognitive and neuroendocrine sequel, and hence focal radiation therapy may be a pragmatic approach. In this age group, high-dose chemotherapy with autologous stem cell rescue may also be considered to defer radiation therapy, but this approach is also associated with significant treatment-related morbidity and mortality

Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

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Yuya Yoshimoto

Full Text Available PURPOSE: There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL activity. METHODS AND MATERIALS: C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD was defined as the time (in days for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. RESULTS: In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days and prolonged median survival time (MST to 59 days (versus 28 days in the non-irradiated group. CD8(+ cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days. Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days, while anti-FR4 and anti-GITR antibodies did not affect efficacy. CONCLUSIONS: Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4

Radiotherapy-Induced Anti-Tumor Immunity Contributes to the Therapeutic Efficacy of Irradiation and Can Be Augmented by CTLA-4 Blockade in a Mouse Model

Science.gov (United States)

Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

2014-01-01

Purpose There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. Methods and Materials C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. Results In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Conclusions Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a

Search for the lowest irradiation dose from literatures on radiation-induced bone tumor

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Yoshizawa, Y; Kusama, T; Morimoto, K [Tokyo Univ. (Japan). Faculty of Medicine

1977-04-01

A survey of past case reports of bone tumor induced by external radiation was carried out with the main object of finding the lowest irradiation dose. Search of the literature published since 1922 revealed 262 cases of radiation-induced bone tumor. These patients, except a patient with occupational exposure, had received radiation for treatment. The primary conditions as object of radiation therapy were nonmalignan bone diseases such as tuberclosis, giant cell tumor, fibrous dysplasia and bone cyst, and extra-skeletal diseases such as retinoblastoma, breast cancer and uterus cancer. The ratio of male to female patients with radiation-induced bone tumor was 1:1.3. The age of the patient ranged between 5 and 98 years, with an average of 37.6 years. Skeletal distribution of radiation-induced bone tumor was as follows: 20% the frontal and face bones, 17% the femur, 10% the humerus, 9% the vertebral column, and 44% other. The lowest absorbed dose reported was 800 rads in patients irradiated for the treatment of bone disease, but 1800 rads in patients with extra-skeletal disease. The latent period ranged between 2 and 42 years, with an average of 11.7 years. The histopathological findings were as follows: 60% osteosarcoma, 25% fibrosarcoma, 7% chondrosarcoma, and 8% other.

Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid

International Nuclear Information System (INIS)

Ambrus, C.M.; Ambrus, J.L.

1975-01-01

Stumptail monkeys (Macaca speciosa) received lethal whole-body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colony-forming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls

Stimulation of anti-tumor effect by low-dose irradiation. Pt. 2. The prolongation of life span in AKR mice

International Nuclear Information System (INIS)

Ishii, Keiichiro; Misonoh, Jun; Hosoi, Yoshio; Ono, Tetsuya; Sakamoto, Kiyohiko.

1994-01-01

To elucidate the antileukemic effect of low-dose X-irradiation, we studied the influence of periodical low-dose X-irradiation on survival and tumor incidence of thymus using AKR mice. The findings of the experiments were as follows; (1) The median survival time of control AKR mice was 283±3 days. It of irradiation group of 15 cGy/week and 30cGy was 309±14 days and 316±10 days respectively. The life span was significantly prolonged (p < 0.05 and p < 0.01 respectively by Wilcoxon test) by periodical low-dose X-irradiation in term of breeding. (2) The incidence of thymus tumor which is observed remarkably in control AKR mice was 48.8%. It of irradiation group of 15 cGy/week and 30 cGy/week was 40% and 20% respectively. Inversely, the non-tumor incidence of tymus in control AKR mice was 19.5%. It of irradiation group of 15 cGy/week and 30 cGy/week was 32.5% and 51.4% respectively. The thymic tumor incidence was significantly decreased (p < 0.01 by chi-square test) in irradiation group of 30 cGy/week. (3) The incidence of thymic lymphoma as a death cause in control AKR mice was 80.4%. It of irradiation group of 15 cGy/week and 30cGy/week was 67.5% and 48.6% respectively. The incidence of thymic lymphoma was significantly decreased (p < 0.05 by chi-square test) in irradiation group of 30 cGy/week. (author)

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

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Fraenzel, W.; Gerlach, R.; Hein, H.J.; Schaller, H.G.

2006-01-01

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 registered or elmex gelee registered . The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In non-irradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 registered or elmex gelee registered led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected, by remineralization than the dentine. (orig.)

VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation

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Fujisawa, Hiroshi; Nakajima, Nakako Izumi; Sunada, Shigeaki; Lee, Younghyun; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira; Uesaka, Mitsuru; Okayasu, Ryuichi

2015-01-01

High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages. We previously reported that complex DNA double-strand breaks produced by high LET radiation enhanced DNA end resection, and this could lead to higher kinase activity of ATR protein recruited to RPA-coated single-stranded DNA. Although the effect of ATR inhibition on cells exposed to low LET gamma-rays has recently been reported, little is known regarding the effect of ATR inhibitor on cells treated with high LET radiation. The purpose of this study is to investigate the effects of the ATR inhibitor VE-821 in human tumor and normal cells irradiated with high LET carbon ions. HeLa, U2OS, and 1BR-hTERT (normal) cells were pre-treated with 1 μM VE-821 for 1 hour and irradiated with either high LET carbon ions or X-rays. Cell survival, cell cycle distribution, cell growth, and micronuclei formation were evaluated. VE-821 caused abrogation of G2/M checkpoint and forced irradiated cells to divide into daughter cells. We also found that carbon ions caused a higher number of multiple micronuclei than X-rays, leading to decreased cell survival in tumor cells when treated with VE-821, while the survival of irradiated normal cells were not significantly affected by this inhibitor. ATR inhibitor would be an effective tumor radiosensitizer with carbon ion irradiation. The online version of this article (doi:10.1186/s13014-015-0464-y) contains supplementary material, which is available to authorized users

Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways.

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Victoria Ifeadi

Full Text Available BACKGROUND: Death receptors (DR of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTβR was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTβR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not LTβR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L and c-FLIP protein expression, this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can overcome Fas and TRAIL

Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts.

Science.gov (United States)

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; Deweese, Theodore L; Herman, Joseph M

2012-04-01

We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response.

Induction of Harderian gland tumors in mice by heavy ion irradiation

International Nuclear Information System (INIS)

Alpen, E.L.; Powers-Risius, P.; Fry, R.J.M.; Ainsworth, E.J.; DeGuzman, R.J.; Harrison, L.D.; Havens, V.C.

1983-01-01

This project was undertaken as part of the program to evaluate the biological effects of charged particle beams generated by the LBL Bevelac and 184-Inch Synchrocyclotron. Experiments have been designed to investigate the relationship of LET to the effectivenesss of radiation of different qualities to induce tumors; and to study the factors that may influence the shape of the dose-response curve for cancer induction by high-LET radiation. The Harderian gland in mice has been chosen as a model tumor system. Although the total number of cells in these glands is small and the natural incidence is low (approx. 2.7%) they are reasonably susceptible to the induction of tumors by irradiation

STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma

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Geng Ling; Shinohara, Eric T.; Kim, Dong; Tan Jiahuai; Osusky, Kate; Shyr, Yu; Hallahan, Dennis E.

2006-01-01

Purpose: Glioblastoma multiforme (GBM) is a devastating brain neoplasm that is essentially incurable. Although radiation therapy prolongs survival, GBMs progress within areas of irradiation. Recent studies in invertebrates have shown that STI571 (Gleevec; Novartis, East Hanover, NJ) enhances the cytotoxicity of ionizing radiation. In the present study, the effectiveness of STI571 in combination with radiation was studied in mouse models of GBM. Methods and Materials: Murine GL261 and human D54 GBM cell lines formed tumors in brains and hind limbs of C57BL6 and nude mice, respectively. GL261 and D54 cells were treated with 5 μmol/L of STI571 for 1 h and/or irradiated with 3 Gy. Protein was analyzed by Western immunoblots probed with antibodies to caspase 3, cleaved caspase 3, phospho-Akt, Akt, and platelet-derived growth factor receptor (PDGFR) α and β. Tumor volumes were assessed in mice bearing GL261 or D54 tumors treated with 21 Gy administered in seven fractionated doses. Histologic sections from STI571-treated mice were stained with phospho-Akt and phospho-PDGFR β antibodies. Kaplan-Meier survival curves were used to study the response of mice bearing intracranial implants of GL261. Results: STI571 penetrated the blood-brain barrier, which resulted in a reduction in phospho-PDGFR in GBM. STI571-induced apoptosis in GBM was significantly enhanced by irradiation. STI571 combined with irradiation induced caspase 3 cleavage in GBM cells. Glioblastoma multiforme response to therapy correlated with an increase in tumor growth delay and survival when STI571 was administered in conjunction with daily irradiation. Conclusion: These findings suggest that STI571 has the potential to augment radiotherapy and thereby improve median survival

Therapeutic benefits in grid irradiation on Tomotherapy for bulky, radiation-resistant tumors.

Science.gov (United States)

Narayanasamy, Ganesh; Zhang, Xin; Meigooni, Ali; Paudel, Nava; Morrill, Steven; Maraboyina, Sanjay; Peacock, Loverd; Penagaricano, Jose

2017-08-01

Spatially fractionated radiation therapy (SFRT or grid therapy) has proven to be effective in management of bulky tumors. The aim of this project is to study the therapeutic ratio (TR) of helical Tomotherapy (HT)-based grid therapy using linear-quadratic cell survival model. HT-based grid (or HT-GRID) plan was generated using a patient-specific virtual grid pattern of high-dose cylindrical regions using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT-GRID irradiation to an open debulking field of an equivalent dose that result in the same tumor cell SF. TR was estimated from DVH data on ten HT-GRID patient plans with deep seated, bulky tumor. Dependence of the TR values on radiosensitivity of the tumor cells and prescription dose was analyzed. The mean ± standard deviation (SD) of TR was 4.0 ± 0.7 (range: 3.1-5.5) for the 10 patients with single fraction maximum dose of 20 Gy to GTV assuming a tumor cell SF at 2 Gy (SF2 t ) value of 0·5. In addition, the mean ± SD of TR values for SF2 t values of 0.3 and 0.7 were found to be 1 ± 0.1 and 18.0 ± 5.1, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the respective TR values to 2.0 ± 0.2 and 1.2 ± 0.04 for a SF2 t value of 0.5. HT-GRID therapy demonstrates a significant therapeutic advantage over uniform dose from an open field irradiation for the same tumor cell kill. TR increases with the radioresistance of the tumor cells and with prescription dose.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

International Nuclear Information System (INIS)

Yasui, Hironobu; Inanami, Osamu; Asanuma, Taketoshi; Iizuka, Daisuke; Nakajima, Takayuki; Kon, Yasuhiro; Matsuda, Akira; Kuwabara, Mikinori

2007-01-01

Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

Energy Technology Data Exchange (ETDEWEB)

Fraenzel, W. [Dept. of Physics, Martin Luther Univ. Halle (Germany); Gerlach, R. [Univ. Clinic and Policlinic for Radiation Therapy, Martin Luther Univ. Halle (Germany); Hein, H.J. [Univ. Clinic and Policlinic for Orthopaedics and Physical Medicine, Martin Luther Univ. Halle (Germany); Schaller, H.G. [Dept. of Operative Dentistry and Periodontology, Martin Luther Univ. Halle (Germany)

2006-07-01

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 {sup registered} or elmex gelee {sup registered}. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In non-irradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 {sup registered} or elmex gelee {sup registered} led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected, by remineralization than the dentine. (orig.)

Hodgkin's disease as unusual presentation of post-transplant lymphoproliferative disorder after autologous hematopoietic cell transplantation for malignant glioma

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Scelsi Mario

2005-08-01

Full Text Available Abstract Background Post-transplant lymphoproliferative disorder (PTLD is a complication of solid organ and allogeneic hematopoietic stem cell transplantation (HSCT; following autologous HSCT only rare cases of PTLD have been reported. Here, a case of Hodgkin's disease (HD, as unusual presentation of PTLD after autologous HSCT for malignant glioma is described. Case presentation 60-years old man affected by cerebral anaplastic astrocytoma underwent subtotal neurosurgical excision and subsequent high-dose chemotherapy followed by autologous HSCT. During the post HSCT course, cranial irradiation and corticosteroids were administered as completion of therapeutic program. At day +105 after HSCT, the patient developed HD, nodular sclerosis type, with polymorphic HD-like skin infiltration. Conclusion The clinical and pathological findings were consistent with the diagnosis of PTLD.

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

International Nuclear Information System (INIS)

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

1998-01-01

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

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

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Suga, Kazuyoshi

1986-01-01

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

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

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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...

Time-dependent cell disintegration kinetics in lung tumors after irradiation

International Nuclear Information System (INIS)

Chvetsov, Alexei V; Palta, Jatinder J; Nagata, Yasushi

2008-01-01

We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T 1/2 . The half-life T 1/2 is determined using the least-squares fit to the clinical data on lung tumor size variation with time after stereotactic radiotherapy. We show that the tumor volume variation after stereotactic radiotherapy of solitary lung tumors can be approximated by an exponential function. A small constant component in the volume variation does not change with time; however, this component may be the residual irregular density due to radiation fibrosis and was, therefore, subtracted from the total volume variation in our computations. Using computerized fitting of the exponent function to the clinical data for selected patients, we have determined that the average half-life T 1/2 of cell disintegration is 28.2 days for squamous cell carcinoma and 72.4 days for adenocarcinoma. This model is needed for simulating the tumor volume variation during radiotherapy, which may be important for time-dependent treatment planning of proton therapy that is sensitive to density variations

The treatment of tumors by the induction of anemia and irradiation in hyperbaric oxygen

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Sealy, R.; Jacobs, P.; Wood, L.; Levin, W.; Barry, L.; Boniaszczuk, J.; Blekkenhorst, G.

1989-01-01

Because increased effects have been achieved when murine tumors are irradiated after a period of hypoxia and because of anecdotal clinical experiences of an improved result after irradiation of previously anemic patients in hyperbaric oxygen, the relationship between irradiation and increased survival was investigated in seventy-two patients with advanced head and neck or cervical cancer. Anemia was achieved by means of a two-stage isovolemic venesection maintained for seventy-two hours, hemoglobin was returned to a normal level, and treatment in hyperbaric oxygen was started. Marked tumor shrinkage after the induction of anemia and before radiotherapy was seen and was probably disease, site, and hemoglobin level related. As a result, a possible new approach to cancer therapy is suggested. After completion of therapy, the 1-year disease-free survival for patients with head and neck and cervical cancer was not improved, but the 21-month survival for cervical cancer was improved. Further studies are strongly urged

Reemergence of apoptotic cells between fractionated doses in irradiated murine tumors

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Meyn, R.E.; Hunter, N.R.; Milas, L.

1994-01-01

The purpose of this investigation was to follow up our previous studies on the development of apoptosis in irradiated murine tumors by testing whether an apoptotic subpopulation of cells reemerges between fractionated exposures. Mice bearing a murine ovarian carcinoma, OCa-I, were treated in vivo with two fractionation protocols: two doses of 12.5 Gy separated by various times out to 5 days and multiple daily fractions of 2.5 Gy. Animals were killed 4 h after the last dose in each protocol, and the percent apoptosis was scored from stained histological sections made from the irradiated tumors according to the specific features characteristic of this mode of cell death. The 12.5+12.5 Gy protocol yielded a net total percent apoptosis of about 45% when the two doses were separated by 5 days (total dose = 25 Gy), whereas the 2.5 Gy per day protocol yielded about 50% net apoptotic cells when given for 5 days (total dose = 12.5 Gy). These values are to be compared to the value of 36% apoptotic cells that is yielded by large single doses (> 25 Gy). Thus, these results indicate that an apoptotic subpopulation of cells reemerged between the fractions in both protocols, but the kinetics appeared to be delayed in the 12.5+12.5 Gy vs. the multiple 2.5 Gy protocol. This reemergence of cells with the propensity for radiation-induced apoptosis between fractionated exposures is consistent with a role for this mode of cell death in the response of tumors to radiotherapy and may represent the priming of a new subpopulation of tumor cells for apoptosis as part of normal tumor homeostasis to counterbalance cell division. 25 refs., 3 figs., 1 tab

Development, fundamentals and objective of half-body irradiation as a method of systematic tumor therapy

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Eichhorn, H.J.

1988-01-01

A review is given on (1) the development of systemic radiotherapy - total body irradiation as well as sequential half-body irradiation in cases of palliative and curative treatment, resp., (2) radiobiological fundamentals of action and limits of the method, (3) clinical results of upper and lower half-body irradiation, resp., as palliative treatment of solid tumors, (4) studies of the prevention of radiation pneumonitis without decreasing radiation dose and (5) proposals for modification, improvement and combination of upper and lower half-body irradiation with other procedures such as hyperthermia and chemotherapy. 48 refs

Comparison of autologous cell therapy and granulocyte-colony stimulating factor (G-CSF) injection vs. G-CSF injection alone for the treatment of acute radiation syndrome in a non-human primate model

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Bertho, Jean-Marc; Frick, Johanna; Prat, Marie; Demarquay, Christelle; Dudoignon, Nicolas; Trompier, Francois; Gorin, Norbert-Claude; Thierry, Dominique; Gourmelon, Patrick

2005-01-01

Purpose: To compare the efficacy of autologous cell therapy after irradiation combined with granulocyte-colony stimulating factor (G-CSF) injections with G-CSF treatment alone in a heterogeneous model of irradiation representative of an accidental situation. Material and Methods: Non-human primates were irradiated at 8.7 Gy whole-body dose with the right arm shielded to receive 4.8 Gy. The first group of animals received G-CSF (lenograstim) injections starting 6 h after irradiation, and a second group received a combination of G-CSF (lenograstim) injections and autologous expanded hematopoietic cells. Animals were followed up for blood cell counts, circulating progenitors, and bone marrow cellularity. Results: No significant differences were seen between the two treatment groups, whatever the parameter observed: time to leukocyte or platelet recovery and duration and severity of aplasia. Conclusion: Our results indicated that identical recovery kinetic was observed when irradiated animals are treated with G-CSF independently of the reinjection of ex vivo expanded autologous hematopoietic cells. Thus G-CSF injections might be chosen as a first-line therapeutic strategy in the treatment of accidental acute radiation victims

Quality of intraoperative autologous blood withdrawal used for retransfusion after cardiopulmonary bypass.

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Flom-Halvorsen, Hanne I; Øvrum, Eivind; Øystese, Rolf; Brosstad, Frank

2003-09-01

Intraoperative autologous blood withdrawal protects the pooled blood from the deleterious effects of cardiopulmonary bypass. Following reinfusion after cardiopulmonary bypass, the fresh autologous blood contributes to less coagulation abnormalities and reduces postoperative bleeding and the need for allogeneic blood products. However, few data have been available concerning the quality and potential activation of fresh blood stored at room temperature in the operating room. Forty coronary artery bypass grafting patients undergoing a consistent intraoperative and postoperative autotransfusion protocol had a median of 1,000 mL of autologous blood withdrawn before cardiopulmonary bypass. After heparinization the blood was drained from the venous catheter via venous cannula into standard blood bags and stored in the operating room until termination of cardiopulmonary bypass. Samples for hemostatic and inflammatory markers were taken from the pooled blood immediately before it was returned to the patient. There was some activation of platelets in the stored autologous blood, as measured by an increase of beta-thromboglobulin. Indications of thrombin formation, as assessed by plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 were not seen, and there was no fibrinolytic activity. The red blood cells remained intact, indicated by the absence of plasma free hemoglobin. As for the inflammatory response, the levels of the terminal complement complex remained stable, and the cytokines tumor necrosis factor-alpha and interleukin 6 levels were not increased during storage. The complement activation products increased minimally, but remained within normal ranges. Except for slight activation of platelets, there was no indication of coagulation, hemolysis, fibrinolysis, or immunologic activity in the autologous blood after approximately 1 hour of operating room storage. The autologous blood was preserved in a condition of high quality, and retransfusion

Histological and histoenzymatic studies on the cellular immunoreaction in Ehrlich tumor-bearing C3H/He mice exposed to various doses of local irradiation

International Nuclear Information System (INIS)

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

1982-01-01

To examine the relationship between the degree of stromal reaction and the dose of irradiation applied locally to the tumor tissue, Ehrlich tumor was transplanted into the right thighs of C3H/He mice, which were subsequently irradiated with a single dose of 1,000, 2,000, 3,000 or 4,000 rad. The mice were killed 1, 3, 5, 7, 10 or 14 days after irradiation, and the resected tumor tissues were examined histologically and enzymohistochemically. The number of peripheral lymphocytes was also counted. The higher the dose of irradiation, the smaller the number of peripheral lymphocytes was observed. Lymphocytic infiltration around the tumor tissue was most intensive about 7 days after irradiation of any dose. The most intensive lymphocytic reaction was observed in the group exposed to 3,000 rad at 7 day after irradiation. Enzymohistochemical study revealed that the infiltrating lymphocytes were mostly T-lymphocytes. These results suggest that there is an optimal dose that produces the most effective cellular immune response against topical tumor cells. (author)

Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts1

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Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; DeWeese, Theodore L; Herman, Joseph M

2012-01-01

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. RESULTS: Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. CONCLUSIONS: We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response. PMID:22496923

The Use Of Laser Irradiation To Stimulate Adipose Derived Stem Cell Proliferation And Differentiation For Use In Autologous Grafts

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Abrahamse, Heidi

2009-09-01

fluences on ADSC viability and proliferation. This paper reviews the development of MSCs as potential therapeutic interventions such as autologous grafts as well as the contribution of low intensity laser irradiation on the maintenance of these cells.

Significance of Fractionated Administration of Thalidomide Combined With γ-Ray Irradiation in Terms of Local Tumor Response and Lung Metastasis

Science.gov (United States)

Masunaga, Shin-ichiro; Sanada, Yu; Moriwaki, Takahiro; Tano, Keizo; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Watanabe, Tsubasa; Nakagawa, Yosuke; Maruhashi, Akira; Ono, Koji

2014-01-01

Background The aim of this study was to evaluate the significance of fractionated administration of thalidomide combined with γ-ray irradiation in terms of local tumor response and lung metastatic potential, referring to the response of intratumor quiescent (Q) cells. Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumor-bearing mice then received γ-ray irradiation after thalidomide treatment through a single or two consecutive daily intraperitoneal administrations up to a total dose of 400 mg/kg in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and 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 after irradiation, macroscopic lung metastases were enumerated. Results Thalidomide raised the sensitivity of the total cell population more remarkably than Q cells in both single and daily administrations. Daily administration of thalidomide elevated the sensitivity of both the total and Q cell populations, but especially the total cell population, compared with single administration. Daily administration, especially combined with MTH, decreased the number of lung metastases. Conclusion Daily fractionated administration of thalidomide in combination with γ-ray irradiation was thought to be more promising than single administration because of its potential to enhance local tumor response and repress lung metastatic potential. PMID:29147396

Time-dependent cell disintegration kinetics in lung tumors after irradiation

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Chvetsov, Alexei V; Palta, Jatinder J [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Nagata, Yasushi [Department of Therapeutic Radiology and Oncology, Kyoto University, Kyoto (Japan)], E-mail: chvetsov@ufl.edu

2008-05-07

We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T{sub 1/2}. The half-life T{sub 1/2} is determined using the least-squares fit to the clinical data on lung tumor size variation with time after stereotactic radiotherapy. We show that the tumor volume variation after stereotactic radiotherapy of solitary lung tumors can be approximated by an exponential function. A small constant component in the volume variation does not change with time; however, this component may be the residual irregular density due to radiation fibrosis and was, therefore, subtracted from the total volume variation in our computations. Using computerized fitting of the exponent function to the clinical data for selected patients, we have determined that the average half-life T{sub 1/2} of cell disintegration is 28.2 days for squamous cell carcinoma and 72.4 days for adenocarcinoma. This model is needed for simulating the tumor volume variation during radiotherapy, which may be important for time-dependent treatment planning of proton therapy that is sensitive to density variations.

Clinical trial of combination therapy using systemic interleukin-2 infusion and low-dose tumor irradiation for advanced hepatocellular carcinoma

International Nuclear Information System (INIS)

Tsuchida, Tetsuo; Hiragushi, Junji; Asano, Yoshihide

1995-01-01

Although recent progress in surgical techniques and interventional radiology enables patients with hepatocellular carcinoma (HCC) to survive longer, there are still many who cannot receive them due to disease progression. We are currently investigating the therapeutic efficacy of the combination of systemic recombinant interleukin-2 (IL-2) administration and local tumor irradiation for HCC patients in the advanced stage. First, the results of the basic experiment to analyze the optimal dose and timing of IL-2 infusion were demonstrated. Intensive administration of high-dose IL-2 caused acute death, whereas intermittent low-dose IL-2 administration resulted in complete tumor regression followed by the acquisition of tumor-specific immunity. Our data suggested that the tumor-bearing state increased the responsiveness to IL-2 treatment, and that an excessively high-dose regimen is not prerequisite for the optimal IL-2 treatment. With regard to the effectiveness of radiotherapy for HCC, human hepatoma cells exhibited apoptotic death when hepatoma cells were cocultured with LAK cells, or were irradiated in vitro with relatively low-dose irradiation. These results suggested the possible synergistic effect of killer cells and low-dose irradiation. Finally, we presented six eligible cases of advanced HCC treated by combination therapy of IL-2 infusion and local low-dose tumor irradiation. Direct anti-tumor effects were one CR, one MR, two NC, and two PD. One CR case and a NC case have survived now for longer than 40 months. In all cases, NK cell activity increased prominently, and side effects wee mild flu-like symptoms except macroscopic hematuria and moderate VLS-like symptoms in two cases in which therapy was continued for longer than 2 years. Hepatic reserve function like prothrombin time or hepaplastic time improved. The apparent clinical effectiveness of the combination therapy presented here might give promising hints for a new therapeutic strategy for HCC. (author)

Synergistic induction of tumors in NMRI mice by combined fetal X-irradiation with low doses and ethylnitrosourea administered to juvenile offspring

Energy Technology Data Exchange (ETDEWEB)

Schmahl, W.

1988-08-01

Mice were X-irradiated on day 15 of gestation with 0.2, 0.4, 0.8 or 1.6 Gy. Offspring were reared by their mothers and divided into two subgroups at an age of 21 days, one subgroup receiving a single dose (45 mg/kg) of ethylnitrosourea (ENU). All animals were kept ultimately until 22 months to register the long-term tumor pattern. The carcinogenic effects of ENU alone were also studied in two separate experiments. Prenatal X-irradiation with 1.6 Gy mostly abolished the carcinogenic late effects of ENU, with the exception of an almost constant leucosis incidence and an unchanged lung tumor frequency. Lowering the prenatal X-ray dose to 0.8 Gy resulted in a significantly increased rate of liver tumors and ovary tumors. Synergistic effects on various tissues were observed after both 0.4- and 0.2-Gy fetal X-irradiation treatment in combination with postnatal application of ENU. These effects mainly involved a significant increase in the frequency of leucosis and of tumors of the liver, intestine, uterus and ovaries. The greater-than-additive effect in the case of these tumors suggests that low-level prenatal X-irradiation leads to a lasting sensitivity of some tissues towards a subsequent carcinogenic stimulus.

Early reoxygenation in tumors after irradiation: Determining factors and consequences for radiotherapy regimens using daily multiple fractions

International Nuclear Information System (INIS)

Crokart, Nathalie; Jordan, Benedicte F.; Baudelet, Christine; Ansiaux, Reginald; Sonveaux, Pierre; Gregoire, Vincent; Beghein, Nelson; Wever, Julie de; Bouzin, Caroline; Feron, Olivier; Gallez, Bernard

2005-01-01

Purpose: To characterize changes in the tumor microenvironment early after irradiation and determine the factors responsible for early reoxygenation. Methods and Materials: Fibrosarcoma type II (FSaII) and hepatocarcinoma transplantable liver tumor tumor oxygenation were determined using electron paramagnetic resonance oximetry and a fiberoptic device. Perfusion was assessed by laser Doppler, dynamic contrast-enhanced MRI, and dye penetration. Oxygen consumption was determined by electron paramagnetic resonance. The interstitial fluid pressure was evaluated by the wick-in-needle technique. Results: An increase in oxygen partial pressure was observed 3-4 h after irradiation. This increase resulted from a decrease in global oxygen consumption and an increase in oxygen delivery. The increase in oxygen delivery was due to radiation-induced acute inflammation (that was partially inhibited by the antiinflammatory agent diclofenac) and to a decrease in interstitial fluid pressure. The endothelial nitric oxide synthase pathway, identified as a contributing factor at 24 h after irradiation, did not play a role in the early stage after irradiation. We also observed that splitting a treatment of 18 Gy into two fractions separated by 4 h (time of maximal reoxygenation) had a greater effect on tumor regrowth delay than when applied as a single dose. Conclusion: Although the cell cycle redistribution effect is important for treatment protocols using multiple daily radiation fractions, the results of this work emphasize that the oxygen effect must be also considered to optimize the treatment strategy

Investigation of the bystander effect in MRC5 cells after acute and fractionated irradiation in vitro

International Nuclear Information System (INIS)

Soleymanifard, Shokouhozaman; Toossi, Mohammad Taghi Bahreyni; Samani, Roghayeh Kamran; Mohebbi, Shokoufeh

2014-01-01

Radiation-induced bystander effect (RIBE) has been defined as radiation responses observed in nonirradiated cells. It has been the focus of investigators worldwide due to the deleterious effects it induces in nonirradiated cells. The present study was performed to investigate whether acute or fractionated irradiation will evoke a differential bystander response in MRC5 cells. A normal human cell line (MRC5), and a human lung tumor cell line (QU-DB) were exposed to 0, 1, 2, and 4Gy of single acute or fractionated irradiation of equal fractions with a gap of 6 h. The MRC5 cells were supplemented with the media of irradiated cells and their micronucleus frequency was determined. The micronucleus frequency after single and fractionated irradiation did not vary significantly in the MRC5 cells conditioned with autologous or QU-DB cell-irradiated media, except for 4Gy where the frequency of micronucleated cells was lower in those MRC5 cells cultured in the media of QU-DB-exposed with a single dose of 4Gy. Our study demonstrates that the radiation-induced bystander effect was almost similar after single acute and fractionated exposure in MRC5 cells. (author)

Investigation of the bystander effect in MRC5 cells after acute and fractionated irradiation in vitro

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Shokouhozaman Soleymanifard

2014-01-01

Full Text Available Radiation-induced bystander effect (RIBE has been defined as radiation responses observed in nonirradiated cells. It has been the focus of investigators worldwide due to the deleterious effects it induces in nonirradiated cells. The present study was performed to investigate whether acute or fractionated irradiation will evoke a differential bystander response in MRC5 cells. A normal human cell line (MRC5, and a human lung tumor cell line (QU-DB were exposed to 0, 1, 2, and 4Gy of single acute or fractionated irradiation of equal fractions with a gap of 6 h. The MRC5 cells were supplemented with the media of irradiated cells and their micronucleus frequency was determined. The micronucleus frequency after single and fractionated irradiation did not vary significantly in the MRC5 cells conditioned with autologous or QU-DB cell-irradiated media, except for 4Gy where the frequency of micronucleated cells was lower in those MRC5 cells cultured in the media of QU-DB-exposed with a single dose of 4Gy. Our study demonstrates that the radiation-induced bystander effect was almost similar after single acute and fractionated exposure in MRC5 cells.

Autologous stem cell transplantation following high-dose whole-body irradiation of dogs - influence of cell number and fractionation regimes

International Nuclear Information System (INIS)

Bodenberger, U.

1981-01-01

The acute radiation syndrome after a single dose of 1600 R (approx. 12-14 Gy in body midline) and after fractionated irradiation with 2400 R (approx. 18-20 Gy) was studied with regard to fractionation time and to the number of bone marrow cells infused. The acute radiation syndrome consisted of damage to the alimentary tract and of damage to the hemopoietic system. Damage of hemopoiesis was reversible in dogs which had been given a sufficient amount of hemopoietic cells. Furthermore changes in skin and in the mucous membranes occurred. Hemopoietic recovery following infusion of various amounts of bone marrow was investigated in dogs which were irradiated with 2400 R within 7 days. Repopulation of bone marrow as well as rise of leukocyte and platelet counts in the peripheral blood was taken as evidence of complete hemopoietic reconstitution. The results indicate that the acute radiation syndrom following 2400 R TBI and autologous BMT can be controlled by fractionation of this dose within 5 or 7 days. The acute gastrointestinal syndrome is aggravated by infusion of a lesser amount of hemopoietic cells. However, TBI with 2400 R does not require greater numbers of hemopoietic cells for restoration of hemopoiesis. Thus, the hemopoiesis supporting tissue can not be damage by this radiation dose to an essential degree. Longterm observations have not revealed serious late defects which could represent a contraindication to the treatment of malignent diseases with 2400 R of TBI. (orig./MG) [de

Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis.

Science.gov (United States)

Mazzini, Letizia; Mareschi, Katia; Ferrero, Ivana; Vassallo, Elena; Oliveri, Giuseppe; Boccaletti, Riccardo; Testa, Lucia; Livigni, Sergio; Fagioli, Franca

2006-07-01

Our study was aimed to evaluate the feasibility and safety of intraspinal cord implantation of autologous mesenchymal stem cells (MSCs) in a few well-monitored amyotrophic lateral sclerosis (ALS) patients. Seven patients affected by definite ALS were enrolled in the study and two patients were treated for compassionate use and monitored for at least 3 years. Bone marrow was collected from the posterior iliac crest according to the standard procedure and MSCs were expanded ex vivo according to Pittenger's protocol. The cells were suspended in 2 ml autologous cerebrospinal fluid and transplanted into the spinal cord by a micrometric pump injector. The in vitro expanded MSCs did not show any bacterial o fungal contamination, hemopoietic cell contamination, chromosomic alterations and early cellular senescence. No patient manifested major adverse events such as respiratory failure or death. Minor adverse events were intercostal pain irradiation and leg sensory dysesthesia, both reversible after a mean period of 6 weeks. No modification of the spinal cord volume or other signs of abnormal cell proliferation were observed. A significant slowing down of the linear decline of the forced vital capacity was evident in four patients 36 months after MSCs transplantation. Our results demonstrate that direct injection of autologous expanded MSCs into the spinal cord of ALS patients is safe, with no significant acute or late toxicity, and well tolerated. The clinical results seem to be encouraging.

Comparison of the evolution of tumor cells after unique and multiple (accelerated) daily irradiation in mammary carcinoma of C3H mice

International Nuclear Information System (INIS)

Pfersdorff, J.; Sack, H.

1986-01-01

The comparison of two fractionation schemes, i.e. the usual irradiation once a day with 2 Gy (SDF) and the fractionation with 3 times 1.6 Gy per day (MDF) at intervals of at least four hours shows the stronger action of higher fractionation on the destruction of tumor cells and the inhibition of their proliferation kinetics. So the number of pycnotic cells is considerably increased in case of multiple daily irradiation, and the mitosis rate as well as the labelling index show a more significant decrease. In case of one irradiation per day, the number of pycnotic cells increases during radiotherapy, too, but the mitosis rate and the labelling index only decrease until the fifth or sixth treatment day, remaining then unchanged or increasing slightly. This suggests a recurring multiplication of tumor cells already during radiotherapy. The higher efficacy of multiple daily fractionation in rapidly proliferating tumors is proved by the measurements of changing tumor volumes in the living animal during irradiation as well as by the observation of the survival time after irradiation. (orig.) [de

Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice

International Nuclear Information System (INIS)

Zips, Daniel; Hessel, Franziska; Krause, Mechthild; Schiefer, Yvonne; Hoinkis, Cordelia; Thames, Howard D.; Haberey, Martin; Baumann, Michael

2005-01-01

Purpose: Previous experiments have shown that adjuvant inhibition of the vascular endothelial growth factor receptor after fractionated irradiation prolonged tumor growth delay and may also improve local tumor control. To test the latter hypothesis, local tumor control experiments were performed. Methods and materials: Human FaDu and UT-SCC-14 squamous cell carcinomas were studied in nude mice. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 (50 mg/kg body weight b.i.d.) was administered for 75 days after irradiation with 30 fractions within 6 weeks. Tumor growth time and tumor control dose 50% (TCD 50 ) were determined and compared to controls (carrier without PTK787/ZK222584). Results: Adjuvant administration of PTK787/ZK222584 significantly prolonged tumor growth time to reach 5 times the volume at start of drug treatment by an average of 11 days (95% confidence interval 0.06;22) in FaDu tumors and 29 days (0.6;58) in UT-SCC-14 tumors. In both tumor models, TCD 50 values were not statistically significantly different between the groups treated with PTK787/ZK222584 compared to controls. Conclusions: Long-term inhibition of angiogenesis after radiotherapy significantly reduced the growth rate of local recurrences but did not improve local tumor control. This indicates that recurrences after irradiation depend on vascular endothelial growth factor-driven angiogenesis, but surviving tumor cells retain their clonogenic potential during adjuvant antiangiogenic treatment with PTK787/ZK222584

A study on mammary gland tumors in rats born of parents irradiated before mating

International Nuclear Information System (INIS)

Strel'tsova, V.N.; Pavlenko-Mikhajlov, Yu.N.; Oshchepkov, A.B.

1982-01-01

The effect of exposure of male or female rats to radiation 5 days before conception on the frequency of development of mammary tumors in their progeny is described. It was shown that mammary tumor incidence and the rate of their development increase in a population of female rats-descendants of one of parents exposed. Irradiation of would-be mothers produced a stronger blastogenic reaction in their progeny than that of fathers

Immunisation of colorectal cancer patients with autologous tumour cells

DEFF Research Database (Denmark)

Diederichsen, Alice; Stenholm, Anna Catharina Olsen; Kronborg, O

1998-01-01

Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression...... of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled...... the criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80...

Selective tumor cell death induced by irradiated riboflavin through recognizing DNA G-T mismatch.

Science.gov (United States)

Yuan, Yi; Zhao, Yongyun; Chen, Lianqi; Wu, Jiasi; Chen, Gangyi; Li, Sheng; Zou, Jiawei; Chen, Rong; Wang, Jian; Jiang, Fan; Tang, Zhuo

2017-09-06

Riboflavin (vitamin B2) has been thought to be a promising antitumoral agent in photodynamic therapy, though the further application of the method was limited by the unclear molecular mechanism. Our work reveals that riboflavin was able to recognize G-T mismatch specifically and induce single-strand breaks in duplex DNA targets efficiently under irradiation. In the presence of riboflavin, the photo-irradiation could induce the death of tumor cells that are defective in mismatch repair system selectively, highlighting the G-T mismatch as potential drug target for tumor cells. Moreover, riboflavin is a promising leading compound for further drug design due to its inherent specific recognition of the G-T mismatch. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. IV. Actinomycin-d

International Nuclear Information System (INIS)

Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

1979-01-01

Experiments have been carried out to determine the effect of different intervals between the administration of x-radiation (1200 rad) and actinomycin-D (200 μg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle, and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2 x (for KHT) or 4 x (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered intraperitoneally either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For a single administration at this dose level (close to the maximum tolerated dose) actinomycin-D did not produce a significant delay in the growth of any of the tumors. For the RIF-1 and KHT tumors, the growth delays produced by drug/radiation combinations generally were not significantly greater than that produced by irradiation alone. For the EMT6 tumor, great variability in the growth delays of combined modality groups seen, with mean growth delays significantly longer than predicted by the radiation alone data. No consistent dependence on timing between irradiation and drug administration was seen

A comparison study on of tumor cell-killing effects between low-dose-rate β-irradiation of 32P and γ-irradiation of 60Co

International Nuclear Information System (INIS)

Feng Huiru; Tian Jiahe; Ding Weimin; Zhang Jinming; Chen Yingmao

2004-01-01

The paper is to elucidate radiobiological characteristics and radiobiological mechanism in killing tumor cells with low dose rate β-rays and high dose rate γ-rays. HeLa cells were exposed to low-rate β-irradiation of 32 P or high-dose-rate γ-irradiation of 60 Co. Cell response-patterns were compared between two the types of radiations in terms of their inhibition of cell proliferation and cell cycle blockage, evaluated by trypanblue excluded method and flow cytometry, respectively. Results show that there is a different way in growth inhibition effect on HeLa cells between low-dose-rate irradiation of 32 P and high-dose-rate irradiation of 60 Co γ. In exposure to 32 P, the inhibition of cell proliferation in HeLa cell was a prolong course, whereas and the effect was in a more serious and quick way in 60 Co irradiation. Cell cycle arrest in G 2 phase induced by 32 P was lower and more prolong than that induced by 60 Co. The inhibition effect on tumor cells between the two types of radiations is different. Impaired DNA repair system by continuous low-dose-rate radiation might contribute to the final radiation effect of 32 P

Changes in tumor oxygenation during a combined treatment with fractionated irradiation and hyperthermia: an experimental study.

Science.gov (United States)

Zywietz, F; Reeker, W; Kochs, E

1997-01-01

To determine the influence of adjuvant hyperthermia on the oxygenation status of fractionated irradiated tumors. Oxygen partial pressure (pO2) in rat rhabdomyosarcomas (R1H) was measured sequentially at weekly intervals during a fractionated irradiation with 60Co-gamma-rays (60 Gy/20f/4 weeks) in combination with local hyperthermia (8 f(HT) at 43 degrees C, 1 h/4 weeks). Tumors were heated twice weekly with a 2450 MHz microwave device at 43 degrees C, 1 h starting 10 min after irradiation. The pO2 measurements (pO2-histograph, Eppendorf, Germany) were performed in anesthetized animals during mechanical ventilation and in hemodynamic steady state. All tumor pO2 measurements were correlated to measurements of the arterial oxygen partial pressure (paO2) determined by a blood gas analyzer. The oxygenation status of R1H tumors decreased continuously from the start of the combined treatment, with increasing radiation dose and number of heat fractions. In untreated controls a median tumor pO2 of 23 +/- 2 mmHg (mean +/- SEM) was measured. Tumor pO2 decreased to 11 +/- 2 mmHg after 30 Gy + 4 HT (2 weeks), and to 6 +/- 2 mmHg after 60 Gy + 8HT (4 weeks). The increase in the frequency of pO2-values below 5 mmHg and the decrease in the range of the pO2 histograms [delta p(10/90)] further indicated that tumor hypoxia increased relatively rapidly from the start of combined treatment. After 60 Gy + 8HT 48 +/- 5% (mean +/- SEM) of the pO2-values recorded were below 5 mmHg. These findings suggest that adjuvant hyperthermia to radiotherapy induces greater changes in tumor oxygenation than radiation alone [cf. (39)]. This might be of importance for the temporary application of hyperthermia in the course of a conventional radiation treatment.

Usefulness of Daily Fractionated Administration of Wortmannin Combined With γ-Ray Irradiation in Terms of Local Tumor Response and Lung Metastasis

Science.gov (United States)

Masunaga, Shin-ichiro; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Tano, Keizo; Maruhashi, Akira; Ono, Koji

2013-01-01

Background To evaluate the usefulness of fractionated administration of wortmannin combined with γ-ray irradiation in terms of local tumor response and lung metastatic potential, referring to the response of intratumor quiescent (Q) cells. Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumor-bearing mice then received γ-ray irradiation after wortmannin treatment through a single or 4 consecutive daily intraperitoneal administrations up to a total dose of 4 mg/kg in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and 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 after irradiation, macroscopic lung metastases were enumerated. Results Wortmannin raised the sensitivity of Q cells more remarkably than the total cell population in both single and daily administrations. Daily administration of wortmannin elevated the sensitivity of both the total and Q cell populations, but especially the total cell population, compared with single administration. Daily administration, especially combined with MTH, decreased the number of lung metastases. Conclusion Daily fractionated administration of wortmannin in combination with γ-ray irradiation was thought to be more promising than single administration because of its potential to enhance local tumor response and repress lung metastatic potential. PMID:29147327

Utilization of a system of automated radiotherapy of malignant tumors using optimum programs of irradiation

International Nuclear Information System (INIS)

Pavlov, A.S.; Kostromina, K.N.; Fadeeva, M.A.

1983-01-01

The clinical experience in the implementation of optimized irradiation programs is summed up for tumors of different sites with the help of the first serial specimen of the system of automated control over irradiation - Altai-MT. The utilization of the system makes it possible to save time and avoid an error in the implementation of complex irradiation programs as well as to lower the exposure of medical personnel to radiation. Automated programs of irradiation meet the requirements of the conformity and homogeneity of a dose field within a focus of lesion, gradient conditions on the border with normal tissues, the minimization of radiation exposure in critical organs

Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation

International Nuclear Information System (INIS)

Fuller, L.; Flaa, C.; Jaffe, D.; Strauss, J.; Kyriakides, G.K.; Miller, J.

1983-01-01

In long-term well adapted kidney transplant recipients we have found a close correlation between the T helper (TH):T suppressor/cytotoxic (TS/C) subset ratios and the presence of T cells that respond in the autologous mixed lymphocyte reaction (AMLR). In 21 recipients with T cell E rosette levels ranging between 53 and 86% and TH:TS/C ratios between 0.15 to 2.10, ratios of greater than 0.8 correlated with AMLR responses (13/13), and ratios of less than 0.8 with AMLR nonreactivity (7/7). By contrast, the allogeneic MLR showed no apparent correlation with the TH:TS/C ratios or with the AMLR pre- or postoperatively. It was found that the AMLR in 22 of 23 normal individuals was markedly inhibited by autologous T cells obtained from peripheral blood lymphocytes, exposed to 3,000 rad (Tx) and added as a third component to the cultures. In contrast, 13 of 13 kidney transplant recipients failed to exhibit this Tx AMLR inhibitory cell population. The ''naturally occurring'' T inhibitory cells, fractionated by an affinity column chromatography procedure into x-irradiated TH and TS/C subsets, inhibited the AMLR to the same extent as unseparated Tx cells. In cell interchange studies performed in four of five HLA identical donor-recipient pairs the Tx cells of the (normal) donor inhibited the recipient AMLR (immunosuppressed), but recipient Tx cells failed to inhibit the donor AMLR. Finally T cells, primed in AMLR and allogeneic MLR for 10 d were tested for AMLR or allogeneic MLR inhibitory activity. Allogeneic MLR primed x-irradiated cells, inhibited both the AMLR and allogeneic MLR while AMLR x-irradiated primed cells inhibited neither reaction. The Tx AMLR inhibitor found in normal peripheral blood, appears to be a cell that is highly sensitive to the effects of biologic or pharmacologic immunosuppressive agents

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.

Specific inhibition of cytotoxic memory cells produced against uv-induced tumors in uv-irradiation mice

International Nuclear Information System (INIS)

Thorn, R.M.

1978-01-01

Cytotoxic responses of uv-irradiated mice against syngeneic uv-induced tumors were measured by using a 51 Cr-release assay to determine if uv treatment induced a specific reduction of cytotoxic activity. The in vivo and in vitro primary responses against syngeneic tumors and allogeneic cells were unaffected, as was the ''memory'' response (in vivo stimulation, in vitro restimulation) against alloantigens. In contrast, the memory response of uv-treated mice against syngeneic, uv-induced tumors was consistently and significantly depressed. The cytotoxicity generated by tumor cell stimulation in vivo or in vitro was tumor-specific and T cell-dependent. Since the primary response against syngeneic uv-induced tumors produces apparently normal amounts of tumor-specific cytotoxic activity, uv-treated mice may not reject transplanted syngeneic tumors because of too few T effector memory cells. These results imply that, at least in this system, tumor rejection depends mostly on the secondary responses against tumor antigens and that at least one carcinogen can, indirectly, specifically regulate immune responses

Targeting carbonic anhydrase IX by nitroimidazole based sulfamides enhances the therapeutic effect of tumor irradiation: A new concept of dual targeting drugs

International Nuclear Information System (INIS)

Dubois, Ludwig; Peeters, Sarah G.J.A.; Kuijk, Simon J.A. van; Yaromina, Ala; Lieuwes, Natasja G.; Saraya, Ruchi; Biemans, Rianne; Rami, Marouan; Parvathaneni, Nanda Kumar; Vullo, Daniela; Vooijs, Marc; Supuran, Claudiu T.; Winum, Jean-Yves

2013-01-01

Background and purpose: Carbonic anhydrase IX (CAIX) plays an important role in pH regulation processes critical for tumor cell growth and metastasis. We hypothesize that a dual targeting bioreductive nitroimidazole based anti-CAIX sulfamide drug (DH348) will reduce tumor growth and sensitize tumors to irradiation in a CAIX dependent manner. Material and methods: The effect of the dual targeting anti-CAIX (DH348) and its single targeting control drugs on extracellular acidification and radiosensitivity was examined in HT-29 colorectal carcinoma cells. Tumor growth and time to reach 4× start volume (T4×SV) was monitored for animals receiving DH348 (10 mg/kg) combined with tumor single dose irradiation (10 Gy). Results: In vitro, DH348 reduced hypoxia-induced extracellular acidosis, but did not change hypoxic radiosensitivity. In vivo, DH348 monotherapy decreased tumor growth rate and sensitized tumors to radiation (enhancement ratio 1.50) without systemic toxicity only for CAIX expressing tumors. Conclusions: A newly designed nitroimidazole and sulfamide dual targeting drug reduces hypoxic extracellular acidification, slows down tumor growth at nontoxic doses and sensitizes tumors to irradiation all in a CAIX dependent manner, suggesting no “off-target” effects. Our data therefore indicate the potential utility of a dual drug approach as a new strategy for tumor-specific targeting

Tumor-Specific Immunotherapy of Mammary Cancer

National Research Council Canada - National Science Library

Ostrand-Rosenberg, Suzanne

1998-01-01

.... To enhance the activation of CD4(+) T helper cells, autologous mouse mammary tumor cells have been transfected with syngeneic MHC class II genes plus costimulatory and antigen presentation accessory molecules, including B7-1, B7-2...

Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation

International Nuclear Information System (INIS)

Blattmann, C.; Oertel, S.; Thiemann, M.; Weber, K.J.; Schmezer, P.; Zelezny, O.; Lopez Perez, R.; Kulozik, A.E.; Debus, J.; Ehemann, V.

2012-01-01

Osteosarcoma and atypical teratoid rhabdoid tumors are tumor entities with varying response to common standard therapy protocols. Histone acetylation affects chromatin structure and gene expression which are considered to influence radiation sensitivity. The aim of this study was to investigate the effect of the combination therapy with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and irradiation on atypical teratoid rhabdoid tumors and osteosarcoma compared to normal tissue cell lines. Clonogenic assay was used to determine cell survival. DNA double-strand breaks (DSB) were examined by pulsed-field electrophoresis (PFGE) as well as by γH2AX immunostaining involving flow cytometry, fluorescence microscopy, and immunoblot analysis. SAHA lead to an increased radiosensitivity in tumor but not in normal tissue cell lines. γH2AX expression as an indicator for DSB was significantly increased when SAHA was applied 24 h before irradiation to the sarcoma cell cultures. In contrast, γH2AX expression in the normal tissue cell lines was significantly reduced when irradiation was combined with SAHA. Analysis of initial DNA fragmentation and fragment rejoining by PFGE, however, did not reveal differences in response to the SAHA pretreatment for either cell type. SAHA increases radiosensitivity in tumor but not normal tissue cell lines. The increased H2AX phosphorylation status of the SAHA-treated tumor cells post irradiation likely reflects its delayed dephosphorylation within the DNA damage signal decay rather than chromatin acetylation-dependent differences in the overall efficacy of DSB induction and rejoining. The results support the hypothesis that combining SAHA with irradiation may provide a promising strategy in the treatment of solid tumors. (orig.)

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

Science.gov (United States)

Besser, Michal J; Shapira-Frommer, Ronnie; Treves, Avraham J; Zippel, Dov; Itzhaki, Orit; Schallmach, Ester; Kubi, Adva; Shalmon, Bruria; Hardan, Izhar; Catane, Raphael; Segal, Eran; Markel, Gal; Apter, Sara; Nun, Alon Ben; Kuchuk, Iryna; Shimoni, Avichai; Nagler, Arnon; Schachter, Jacob

2009-05-01

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Synchronization of tumor cells with 5-fluorouracil plus uracil and with vinblastine and irradiation of synchronized cultures

International Nuclear Information System (INIS)

Severin, E.; Hagenhoff, B.

1988-01-01

In this article, some arguments are put forward which support the conception of a combined radio-chemotherapy acting by a reversible inhibition of tumor cells with cytostatic drugs in a not cytocidal dose and the following selective killing by irradiation of the cells blocked in a radiosensitive phase. The two cytostatic drugs 5-fluorouracil (FU) and vinblastine (VLB), as inhibitors of DNA synthesis and mitosis, respectively, are tested in vitro both separately and combined in two tumor cell lines of the mouse, i.e. the Ehrlich ascites tumor and the sarcoma S 180. A cell-proliferative and, as far as possible, not cytocidal dose is used because of the inevitable side effects exerted by these drugs on normal tissues. A reversible synchronization of the ascites tumor is achieved even in the young mouse by FU in a dose of 15 ng to 500 ng (applied seven times every two hours), if the synchronization is controlled by applying the antimetabolite together with uracil in an equimolar concentration and then stimulating the growth of the cells inhibited during DNA synthesis by the administration of thymidine. The statistical analysis of dose-effect curves after X-ray irradiation shows an increased radiosensitivity of the synchronized cell population, provided that the optimum moment had been chosen for the irradiation. (orig.) [de

Combined effect of carcinogenic n-nitrosodimethylamine precursors and fractioned {gamma}-irradiation on tumor development in rats.; Kombinirovannoe vliyanie predshestvennikov kantserogennogo N-nitrozodimetilamina i fraktsionirovannogo {gamma}-oblucheniya na vozniknovenie opukholej u krys.

Energy Technology Data Exchange (ETDEWEB)

Galenko, P M [Yinstitut Eksperimental` noyi Patologyiyi, Onkologyiyi yi Radyiobyiologyiyi, Natsyional` na Akademyiya Nauk Ukrayini, Kyiv (Ukraine); Nedopitanskaya, N N [Yinstitut Zdorov` ya, Myinyisterstvo Okhoroni Zdorov` ya, Kyiv (Ukraine)

1996-12-01

The influence of combined action of N-nitrosodimethylamine (NDMA) and fractioned {gamma}-irradiation on tumor development in rats was investigated. Both the tumor frequency and tumor plurality coefficient have been studied for two types of treatment: precursors of NDMA (amidopyrine and/or sodium nitrite (SN)) alone and the combination `precursors plus radiation`. Tumor frequency decreased by about 11% after combination of {gamma}-irradiation and precursors in comparison with precursors alone. Nevertheless, treatment with SN and {gamma}-irradiation did not change tumor frequency in comparison with SN alone. Irradiation of rats treated with precursors led to an increased tumor plurality coefficient.

Can loco-regional irradiation be a routine supplement to high dose chemotherapy with autologous bone marrow transplant in women with poor prognosis breast cancer

International Nuclear Information System (INIS)

Wobeck, Linda K.; Holland, H. Kent; Landry, Jerome C.; Lynn, Michael J.; Hughes, Lorie L.

1997-01-01

Purpose: High dose chemotherapy followed by bone marrow transplantation (BMT) is currently being performed in many women with localized, poor prognosis breast cancer. The purpose of this study was to examine patterns of care in radiation treatment as well as acute side effects in women who received breast or chest wall and regional nodal irradiation (XRT) post BMT. Methods: The records of 126 consecutive women with localized, poor prognosis breast cancer who received an autologous BMT at Emory University between (3(90)) and (7(96)) were retrospectively reviewed. Results: All 126 women underwent high dose chemotherapy with cyclophosphamide, carboplatinum and thiotepa followed by BMT. Loco - regional XRT after BMT was routinely recommended for patients with 10 or more positive axillary lymph nodes or inflammatory carcinoma. Overall, 90 patients received local +/- regional XRT; 11 patients prior to BMT and 79 patients post BMT. Three of these patients had a local relapse prior to beginning XRT post BMT. Thirty six patients did not receive XRT for the following reasons: major post BMT morbidity or insufficient hematological recovery (15 patients), less than 10 positive axillary lymph nodes (12 patients), or refusal/not referred (9 patients). Therefore, of the 103 patients (excludes those with less than 10 positive nodes) intended to receive post BMT irradiation, 14.5 % (15 patients- 2 with inflammatory carcinoma) were unable to receive it secondary to post BMT morbidity and 9% (9 patients) refused or were not referred. Of these 79 patients irradiated post BMT, 16 had stage IIA, 20 stage IIB, 27 stage IIIA and 16 inflammatory carcinoma (IIIB). The median time from transplant to irradiation was 82 days (range 44 - 641). Average dose to breast or chest wall was 49.5 Gy (range 42-55.8 Gy). Boost dose (mean 12 Gy, range 10-22 Gy) was given in 62% of patients. The median tumor bed/mastectomy scar dose was 60 Gy (range 42-72 Gy). Supraclavicular, posterior axillary and

Dose distribution of non-coplanar irradiation

Energy Technology Data Exchange (ETDEWEB)

Fukui, Toshiharu; Wada, Yoichi; Takenaka, Eiichi

1987-02-01

Non-coplanar irradiations were applied to the treatment of brain tumor. The dose distribution around the target area due to non-coplanar irradiation was half less than the dose when coplanar irradiation used. Integral volume dose due to this irradiation was not always less than that due to conventional opposing or rotational irradiation. This irradiation has the better application to the following;as a boost therapy, glioblastoma multiforme;as a radical therapy, recurrent brain tumor, well differentiated brain tumor such as craniopharyngioma, hypophyseal tumor etc and AV-malformation.

Role of Tertiary Lymphoid Structures (TLS) in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

Energy Technology Data Exchange (ETDEWEB)

Pimenta, Erica M. [Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States); Barnes, Betsy J., E-mail: barnesbe@njms.rutgers.edu [Department of Biochemistry and Molecular Biology, Rutgers Biomedical and Health Sciences, New Jersey Medical School-Cancer Center, Newark, NJ 07103 (United States)

2014-04-23

Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin{sup ®}) and rituximab (Rituxan{sup ®})) and the first approved cancer vaccine, Provenge{sup ®} (sipuleucel-T), investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS) within the tumor microenvironment may be used to enhance immunotherapy response.

Role of Tertiary Lymphoid Structures (TLS in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers

Directory of Open Access Journals (Sweden)

Erica M. Pimenta

2014-04-01

Full Text Available Following the successes of monoclonal antibody immunotherapies (trastuzumab (Herceptin® and rituximab (Rituxan® and the first approved cancer vaccine, Provenge® (sipuleucel-T, investigations into the immune system and how it can be modified by a tumor has become an exciting and promising new field of cancer research. Dozens of clinical trials for new antibodies, cancer and adjuvant vaccines, and autologous T and dendritic cell transfers are ongoing in hopes of identifying ways to re-awaken the immune system and force an anti-tumor response. To date, however, few consistent, reproducible, or clinically-relevant effects have been shown using vaccine or autologous cell transfers due in part to the fact that the immunosuppressive mechanisms of the tumor have not been overcome. Much of the research focus has been on re-activating or priming cytotoxic T cells to recognize tumor, in some cases completely disregarding the potential roles that B cells play in immune surveillance or how a solid tumor should be treated to maximize immunogenicity. Here, we will summarize what is currently known about the induction or evasion of humoral immunity via tumor-induced cytokine/chemokine expression and how formation of tertiary lymphoid structures (TLS within the tumor microenvironment may be used to enhance immunotherapy response.

Anti-tumor effect of adenovirus-mediated suicide gene therapy under control of tumor-specific and radio-inducible chimeric promoter in combination with γ-ray irradiation in vivo

International Nuclear Information System (INIS)

Sun Wenjie; Yu Haijun; Xiongjie; Xu Yu; Liao Zhengkai; Zhou Fuxiang; Xie Conghua; Zhou Yunfeng

2011-01-01

Objective: To detect the selective inhibitory effects of irradiation plus adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic acid (IAA) suicide gene system using tumor-specific and radio-inducible chimeric promoter on human hepatocellular carcinoma subcutaneously xenografted in nude mouse. Methods: Recombinant replicated-deficient adenovirus vector containing HRP gene and chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 radio-inducible CArG elements was constructed. A human subcutaneous transplanting hepatocellular carcinoma (MHCC97 cell line) model was treated with γ-ray irradiation plus intra-tumor injections of adenoviral vector and intra-peritoneal injections of prodrug IAA. The change of tumor volume and tumor growth inhibiting rate, the survival time of nude mice, as well as histopathology of xenograft tumor and normal tissues were evaluated. Results: Thirty one days after the treatment, the relative tumor volumes in the negative, adenovirus therapy, irradiation, and combination groups were 49.23±4.55, 27.71±7.74, 28.53±10.48 and 11.58±3.23, respectively.There was a significantly statistical difference among them (F=16.288, P<0.01).The inhibition effect in the combination group was strongest as compared with that in other groups, and its inhibition ratio was 76.5%. The survival period extended to 43 d in the combination group, which showed a significantly difference with that in the control group (χ 2 =18.307, P<0.01). The area of tumors necrosis in the combination group was larger than that in the other groups, and the normal tissues showed no treatment-related toxic effect in all groups. However, multiple hepatocellular carcinoma metastases were observed in the liver in the control group, there were a few metastases in the monotherapy groups and no metastasis in the combination group. Conclusions: Adenovirus-mediated suicide gene therapy plus radiotherapy dramatically could inhibit tumor growth and prolong

Time distributions of recurrences of immunogenic and nonimmunogenic tumors following local irradiation

International Nuclear Information System (INIS)

Suit, H.D.; Sedlacek, R.; Fagundes, L.; Goitein, M.; Rothman, K.J.

1978-01-01

Three hundred and fourteen mice received single-dose irradiation of the right leg and thigh as treatment of an 8-mm mammary carcinoma isotransplant, and were then observed until death, usually by 1000 days. The time distributions of death due to local recurrence, radiation-induced sarcoma, distant metastasis in the absence of local regrowth, second primary, intercurrent disease, and unknown causes have been evaluated. The times for the transplant tumor inoculum to grow to an 8-mm tumor and the times of death due to local regrowth, distant metastasis, or induced tumor were all approximately log-normally distributed. Of the 128 recurrences, the latest-appearing 3 were at 300, 323, and 436 days; no recurrences were noted during the time period from 436 to 1000 days. These findings have been interpreted to mean that in some cases absolute cure of mice of the tumor in the leg was achieved by radiation alone at the dose levels employed. Radiation-induced sarcomas began to appear after 300 days. The time of appearance of the radiation-induced tumors was inversely related to radiation dose. Similar data for an immunogenic fibrosarcoma show that recurrences appeared earlier and were more closely bunched with respect to time than the recurrences of mammary carcinoma. The time distribution of the development of radiation-induced tumors in non-tumor-bearing animals was also approximately long-normally distributed; the slope of the time distribution curve was the same as that for radiation-induced tumors in mice which had been treated for tumor

Effect of Irradiation on Tumor Microenvironment and Bone Marrow Cell Migration in a Preclinical Tumor Model

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Kane, Jonathan L. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Hanna, Alaa [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Raffel, Thomas R. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Wilson, George D. [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Marples, Brian, E-mail: Brian.Marples@beaumont.edu [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States)

2016-09-01

Purpose: To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. Methods and Materials: Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy using a 5 days on, 2 days off schedule to mimic clinical delivery. Radiation-induced tumor microenvironment changes were examined after treatment using flow cytometry and antibody-specific histopathology. Normal tissue effects were measured using noninvasive {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography after naïve animals were given whole-lung irradiation to 40 Gy in 4 weeks using the same 2-Gy/d regimens. Results: Over the 2 weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate (0.31 ± 0.02 mm{sup 3}/d and 0.55 ± 0.04 mm{sup 3}/d, respectively; P<.007). Histopathology showed a significant comparative reduction in the levels of Ki-67 (14.5% ± 3%), hypoxia (10% ± 3.5%), vascular endothelial growth factor (2.3% ± 1%), and stromal-derived factor-1α (2.5% ± 1.4%), as well as a concomitant decrease in CD45{sup +} bone marrow–derived cell (BMDC) migration (7.8% ± 2.2%) after PRT. The addition of AMD3100 also decreased CD45{sup +} BMDC migration in treated tumors (0.6% ± 0.1%). Higher vessel density was observed in treated tumors. No differences were observed in normal lung tissue after PRT or SRT. Conclusions: Pulsed RT–treated tumors exhibited slower growth and reduced hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by tumors in low oxygen microenvironments, including angiogenesis and recruitment of BMDCs.

Hemithorax irradiation for Ewing tumors of the chest wall

International Nuclear Information System (INIS)

Schuck, Andreas; Ahrens, Susanne; Konarzewska, Agnieszka; Paulussen, Michael; Froehlich, Birgit; Koenemann, Stefan; Ruebe, Christian; Ruebe, Claudia E.; Dunst, Juergen; Willich, Normann; Juergens, Heribert

2002-01-01

Purpose: In the Cooperative Ewing's Sarcoma Study 86 and the European Intergroup Cooperative Ewing's Sarcoma Study 92, hemithorax irradiation (RT) was performed in patients with Ewing tumors of the chest wall involving the pleura or contaminating the pleural cavity. In a retrospective analysis, the outcomes of these patients were evaluated and compared with those of patients with chest wall tumors who did not receive hemithorax RT. Methods and Materials: Between 1985 and 1996, 138 patients presented with nonmetastatic Ewing tumors of the chest wall. They were treated in a multimodal treatment regimen that included polychemotherapy and local therapy depending on the tumor characteristics. Hemithorax RT was performed at a dose of 15 Gy for patients <14 years old and 20 Gy for patients ≥14 years old. Forty-two patients received hemithorax RT (Group 1) and 86 patients did not (Group 2). The data were insufficient for the other 10 patients. Results: Comparing both groups, the initial pleural effusion, pleural infiltration, and intraoperative contamination of the pleural space were significantly more frequent in Group 1. The event-free survival rate after 7 years was 63% for patients in Group 1 and 46% for patients in Group 2 (not statistically significant). The 7-year local relapse rate (including combined local-systemic relapses) was 12% in Group 1 and 10% in Group 2; the corresponding systemic relapse rates were 22% and 39%. Conclusion: Patients with chest wall tumors who received hemithorax RT were negatively selected; yet the rate of event-free survival was better for patients who received hemithorax RT than for those who did not (although the difference was not statistically significant). This result was due to a reduction of metastases, mainly lung metastases. Local control was equivalent between the two groups. These favorable results have caused us to continue using hemithorax RT to treat high-risk patients with Ewing tumors of the chest wall

Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

International Nuclear Information System (INIS)

Li, Wende; Huang, Peigen; Chen, David J.; Gerweck, Leo E.

2014-01-01

Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs −/− ) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD 50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

Autologous Fat Injection for Augmented Mammoplasty

International Nuclear Information System (INIS)

Yoon, Eul Sik; Seo, Bo Kyoung; Yi, Ann; Cho, Kyu Ran

2008-01-01

Autologous fat injection is one of the methods utilized for augmented mammoplasty methods. In this surgical procedure, the fat for transfer is obtained from the donor site of the patient's own body by liposuction and the fat is then injected into the breast. We report here cases of three patients who underwent autologous fat injection. Two of the patients had palpable masses that were present after surgery. The serial imaging findings and surgical method of autologous fat transfer are demonstrated

Effects of ionizing irradiation on the estradiol and progesterone receptors in rat mammary tumors

International Nuclear Information System (INIS)

Janssens, J.P.; Wittevrongel, C.; Van Dam, J.; Goddeeris, P.; Lauwerijns, J.M.; De Loecker, W.

1981-01-01

The determination of estradiol and progesterone receptor concentrations in mammary tumors is useful in predicting the hormone responsiveness. As this assay is carried out on tumor tissue which may have been subjected to radiotherapy, the possibility of an ionizing irradiation affecting the steroid receptor levels in neoplastic tissue should be taken into account. The steroid receptor concentrations are examined in dimethylbenz(a)anthracene-induced tumors os Sprague-Dawley rats. The estradiol and the progesterone receptor titers become reduced significantly after treatment with 20 Gray while an application with 7 Gray does not affect the titer values. After treatment of the tumor with 20 Gray, the steroid receptor concentrations decrease progressively, reaching a maximal reduction 20 to 30 days after exposure. As radiation treatment affects the receptor concentrations, this should be kept in mind when interpreting the steroid receptor concentrations

Clinical efficacy of sunitinib combined with autologous DC and CIK for patients with metastatic renal cell carcinoma

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Liang ZHANG

2014-01-01

Full Text Available Objective　To analyze the clinical efficacy and safety of sunitinib combined with autologous dentritic cell (DC and cytokine induced killer cell (CIK for patients suffering from metastatic renal cell carcinoma (mRCC. Methods　Clinical data of 27 mRCC patients treated with sunitinib combined with autologous DC and CIK were reviewed retrospectively. Efficacy, quality of life, immunology and safety of this treatment were evaluated. Results　Follow-up time ranged from 4 to 25 months. Out of all the patients, sunitinib was reduced in 1 and discontinued in 2 due to side effects; 1 patient quit for personal reasons; 14 patients developed progressive disease. The progression-free survival (PFS was 4 to 19.5 months. Ten patients died from tumor, the overall survival time (OS was 6 to 21 months. The median PFS was 16 months (95%CI 12.5-19.5. The OS was not achieved. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST. All the patients received treatment over 1 cycle. After one course of treatment, among 27 patients, 0 had complete remission (CR, 4 had partial remission (PR, 17 had stable disease (SD, and 6 had progressive disease (PD. The overall objective remission rate (ORR and disease control rate (DCR were 14.8% (4/27 and 77.8% (21/27, respectively. Sunitinib and autologous transfusion of DC and CIK improved the immune function and quality of life. The major adverse events were fatigue, hand-foot syndrome, hypertension, hypothyroidism, thrombocytopenia, neutropenia and fever. Most of the adverse events were ameliorated by supportive treatment or dose reduction. Conclusions　 Sunitinib combined with autologous DC and CIK may be beneficial in the treatment of mRCC with acceptable toxic reactions, and it may be considered as a new approach for the comprehensive treatment of RCC. DOI: 10.11855/j.issn.0577-7402.2013.12.06

Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation

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An Zhu; Shaeffer, James; Leslie, Susan; Kolm, Paul; El-Mahdi, Anas M.

1996-01-01

Purpose: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. Methods and Materials: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. Results: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p = 0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. Conclusion: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas

Irradiation sequels of retinoblastomas. Sequelles de l'irradiation externe des retinoblastomes

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Benk, V; Habrand, J L; Bloch Michel, E; Soussaline, M; Sarrazin, D [Centre de Lutte Contre le Cancer Gustave-Roussy, 94 - Villejuif (France)

1993-01-01

From 1975 to 1985, 34 children with a non-metastatic retinoblastoma were irradiated at the Institut Gustave-Roussy. After enucleation, 19 bilateral tumors were irradiated by two lateral opposed fields and 15 unilateral tumors by one lateral and anterior field, in the case of optic nerve being histologically positive. Dose was 45 Gy, 1.8 Gy per fraction. The 10-year-survival rate for unilateral and bilateral retinoblastomas was 79%. Long term sequels were available for 25 patients: 88% retained one functional eye. Three children with bilateral retinoblastomas developed a cataract in the residual eye between 2 and 5 years after irradiation, none with unilateral tumor. Nine patients (36%), seven with unilateral and two with bilateral tumor developed a cosmetical problem that required multiple surgical rehabilitation between 3 and 14 years after irradiation. Nine children (36%), five with unilateral and four with bilateral tumors developed growth hormone deficit between 2 and 8 years after irradiation that required hormone replacement. Their pituitary gland received 22 to 40 Gy. No osteosarcoma occurred in this population. Among long-term sequels, following irradiation for retinoblastoma, cosmetical deformities represent disabling sequels that could justify new approaches in radiotherapy, as protontherapy combined with 3-D-treatment planning.

Characterization of ex vivo expanded tumor infiltrating lymphocytes from patients with malignant melanoma for clinical application

DEFF Research Database (Denmark)

Junker, Niels; Thor Straten, Per; Andersen, Mads Hald

2011-01-01

Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis......Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have...

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

International Nuclear Information System (INIS)

Deeg, H.J.; Storb, R.; Weiden, P.L.; Schumacher, D.; Shulman, H.; Graham, T.; Thomas, E.D.

1981-01-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

Autologous stem-cell transplantation in Hodgkin’s lymphoma: analysis of a therapeutic option

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Adriano de Moraes Arantes

2011-06-01

Full Text Available Objective: To report the clinical progress of patients with Hodgkin’slymphoma treated with autologous transplantation after failure orrelapse of first-line treatment with chemotherapy and/or radiationtherapy. Methods: The results of a retrospective analysis of 31patients submitted to autologous transplantation as second-linetreatment, between April 2000 and December 2008, were analyzed.Fourteen men and seventeen women, with a median age of 27 years,were submitted to autologous transplantation for relapsed (n = 21or refractory (n = 10 Hodgkin’s lymphoma. Results: Mortalityrelated to treatment in the first 100 days after transplant was 3.2%.With a mean follow-up period of 18 months (range: 1 to 88 months,the probability of global survival and progression-free survival in18 months was 84 and 80%, respectively. The probability of globalsurvival and progression-free survival at 18 months for patients withchemosensitive relapses (n = 21 was 95 and 90%, respectively,versus 60 and 45% for patients with relapses resistant to chemotherapy(n = 10 (p = 0.001 for global survival; p = 0.003 for progressionfreesurvival. In the multivariate analysis, absence of disease or pretransplant disease < 5 cm were favorable factors for global survival (p= 0.02; RR: 0.072; 95%CI: 0.01-0.85 and progression-free survival (p= 0.01; RR: 0.040; 95%CI: 0.007-0.78. Conclusion: Autologous transplantation of stem-cells is a therapeutic option for Hodgkin’s lymphoma patients after the first relapse. Promising results were observed in patients with a low tumor burden at transplant.

Study on construction of pEgr-hPTEN expression vector induced by irradiation and its anti-tumor effect in vitro

International Nuclear Information System (INIS)

Tian Mei; Jin Guanghui; Piao Chunji; Li Xiuyi; Liu Linlin

2003-01-01

Objective: To clone the cDNA of human tumor suppressor gene-PTEN, construct pEgr-hPTEN expression vector induced by irradiation and study its inhibitory effect on proliferation of malignant glioma cell line SHG-44 transfected steadily with pEgr-hPTEN after different doses of X-ray irradiation. Methods: A DNA fragment about 1200 bp, PTEN, was amplified from human placenta tissues by using RT-nested PCR and was cloned into pUCm-T vector after automatic sequencing, then the fragment was inserted into a vector pcD-NA3.1-Egr to construct an expression vector pEgr-hPTEN. pEgr-hPTEN was transfected into SHG-44 cells in vitro. Stably transfected cell line SHG-44-sPTEN was selected through G418. The inhibitor effect on SHG-44-sPTEN was observed after different doses of X-ray irradiation in vitro. Results: The PTEN cDNA has been cloned correctly and its expression vector pEgr-hPTEN was also constructed. Growth of SHG-44 cells was inhibited significantly by stable pEgr-hPTEN transfection combined with X-ray irradiation. With the increase of dose, the inhibitory effect was enhanced within 5 Gy. Conclusion: Human tumor suppressor gene-PTEN cDNA has been cloned and its expression vector has been constructed. The tumor was inhibited significantly by gene-radiotherapy in vitro. The result provides the theoretical and experimental basis for improvement of clinical radiotherapeutic effect on tumors

Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

Science.gov (United States)

Osada, Takuya; Nagaoka, Koji; Takahara, Masashi; Yang, Xiao Yi; Liu, Cong-Xiao; Guo, Hongtao; Roy Choudhury, Kingshuk; Hobeika, Amy; Hartman, Zachary; Morse, Michael A; Lyerly, H Kim

2015-05-01

Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optimized combination of reagents and loaded with tumor-derived antigens using a clinically feasible electroporation strategy would induce potent antitumor immunity. We first studied the effects on DC maturation and antigen presentation of the addition of picibanil (OK432) to a combination of zoledronic acid, tumor necrosis factor-α, and prostaglandin E2. Using DC matured with the optimized combination, we tested 2 clinically feasible sources of autologous antigen for electroloading, total tumor mRNA or total tumor lysate, to determine which stimulated more potent antigen-specific T cells in vitro and activated more potent antitumor immunity in vivo. The combination of tumor necrosis factor-α/prostaglandin E2/zoledronic acid/OK432 generated DC with high expression of maturation markers and antigen-specific T-cell stimulatory function in vitro. Mature DC electroloaded with tumor-derived mRNA [mRNA electroporated dendritic cell (EPDC)] induced greater expansion of antigen-specific T cells in vitro than DC electroloaded with tumor lysate (lysate EPDC). In a therapeutic model of MC38-carcinoembryonic antigen colon cancer-bearing mice, vaccination with mRNA EPDC induced the most efficient anti-carcinoembryonic antigen cellular immune response, which significantly suppressed tumor growth. In conclusion, mature DC electroloaded with tumor-derived mRNA are a potent cancer vaccine, especially useful when specific tumor antigens for vaccination have not been identified, allowing autologous tumor, and if unavailable, allogeneic cell lines to be used as an unbiased source of antigen. Our data support clinical testing of this strategy.

Recycling of extracorporeally irradiated autograft for malignant bone tumors: long-term follow-up.

Science.gov (United States)

Kotb, Samir Z; Mostafa, Mohamed F

2013-11-01

This study was conducted to evaluate the long-term oncological and functional outcomes. Forty-two patients (29 men and 13 women) with primary malignant bone tumors were included in this study. The procedure consisted of wide en bloc resection, clearing the extraosseous soft tissue and medullary content, extracorporeal irradiation with a single dose of 50 Gy using linear accelerator, and reimplantation using suitable fixation devices. The mean survivor follow-up was 54 months (24-174 months). There were 32 (76.2%) patients continuously disease free, 7 (16.7%) died of disease, and 3 (7.1%) alive with disease. Local recurrence was encountered in 4 (9.5%) patients. Nonunion occurred at 3 (6.4%) osteotomy sites. Deep infection developed in 4 (9.5%) cases. There were 13 patients rated excellent, 17 good, 10 fair, and 2 failures according to the Mankin scoring system. The mean ratings of the Musculoskeletal Tumor Society score and the Toronto Extremity Salvage Score were 77 and 81, respectively. The long-term oncological and functional results are encouraging and suggest that extracorporeal irradiation and reimplantation can be a long-lasting biological reconstructive technique in properly selected patients.

Re-irradiation associated to cetuximab and paclitaxel in the recurrences in irradiated field of upper aero-digestive ducts tumors resistant to platina salts; Re-irradiation associee au cetuximab et au paclitaxel dans les recidives en territoire irradie des tumeurs des voies aero-digestives superieures resistantes aux sels de platine

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Martin, L.M. [Centre Guillaume-Le-Conquerant, 76 - Le Havre (France); Moran, A.R.; Pavlovitch, J.M. [Clinique du Petit-Colmoulin, 76 - Harfleur (France); El Amarti, R. [Hopital Monod, 76 - Montivilliers (France); Damour, M. [CMC Ormeaux-Vauban, 76 - Le Havre (France)

2007-11-15

The objective of this study is to present the preliminary results of the toxicity and efficiency evaluation of the association 're-irradiation-cetuximab-paclitaxel' in the recurrences of upper aero-digestive ducts tumors in irradiated field resistant to platinum salts. (N.C.)

Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.

Science.gov (United States)

Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Hayashi, Katsuhiro; Yamamoto, Norio; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki

2017-05-01

There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas. Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed. In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively. Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society. © 2017 American Cancer Society.

Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

Science.gov (United States)

Pigott, J H; Ishihara, A; Wellman, M L; Russell, D S; Bertone, A L

2013-01-01

To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain. There were not any significant differences between autologous and genetically modified autologous MSC for synovial fluid total nucleated cell count, total protein, interleukin (IL)-6, IL-10, fetlock circumference, oedema score, pain-free range-of-motion, and soluble gene products that were detected for at least two days. Allogeneic and xenogeneic MSC produced a greater increase in peak of inflammation at 24 hours than either autologous MSC group. Genetically engineered MSC can act as vehicles to deliver gene products to the joint; further investigation into the therapeutic potential of this cell therapy is warranted. Intra-articular MSC injection resulted in a moderate acute inflammatory joint response that was greater for allogeneic and xenogeneic MSC than autologous MSC. Clinical management of this response may minimize this effect.

ELISA quantification of CCI-103F binding in canine tumors prior to and during irradiation

International Nuclear Information System (INIS)

Thrall, D.E.; McEntee, M.C.; Cline, J.M.; Raleigh, J.A.

1994-01-01

The purpose of this work was to evaluate injections of CCI-103F, a marker of hypoxia, as a method to quantify alterations in tumor hypoxia during irradiation. Twelve dogs with spontaneous solid tumors were given intravenous CCI-103F, and tumor biopsies were taken at various times after injection. CCI-103F antigen concentration was quantified by ELISA. Four of the dogs were given one injection of CCI-103F, and the other eight received two injections. In dogs receiving two injections, CCI-103F was administered before irradiation and 7 days later, following a total dose of 15.0 Gy. Plasma CCI-103F pharmacokinetics were assessed in dogs receiving two injections. CCI-103F antigen was detectable in the initial biopsy in each of the four dogs receiving one injection, and the amount of detectable antigen decreased in subsequent biopsies with an initial half life of approximately 19 h. This suggests that multiple injections of CCI-103F could be used in the same subject to monitor tumor hypoxia as a function of time or during a course of treatment. In the eight dogs receiving two injections of CCI-103F, the CCI-103F antigen concentration in the 24 h samples ranged from 4.66-151.9 μmole CCI-103F antigen/kg tumor, a difference of a factor of approximately 33. The ratio of maximum to minimum concentration of CCI-103F antigen in 51 paired biopsy samples ranged from 1.01-4.07, with a mean of 1.67. Seventy-five percent of the ratios were ≤ 2.02. There was no apparent relationship between the magnitude of the ratio, i.e., intratumoral variation, and tumor volume or the absolute tumor concentration of CCI-103F antigen in dogs given two injections of CCI-103F was consistent with little change in pretreatment oxygen status in six dogs, and an increase in tumor oxygenation in two dogs. It appears possible to obtain an estimate of the change in tumor hypoxia over time by assaying biopsies for CCI-103F concentration. 31 refs., 7 figs., 3 tabs

Head and neck tumors and impaired mental function following scalp irradiation

International Nuclear Information System (INIS)

Modan, B.; Ron, E.; Werner, A.; Yaar, I.

1977-01-01

This is a second report of a comprehensive case-control study of 11,000 individuals subjected to scalp x-irradiation in childhood between 1949 and 1960. Follow up was conducted through the following national records: Tumor, Registry, Central Population Registry, Mental Health Registry, Nationwide High School Aptitude Test, Police, Ministry of Welfare and the Army. In addition, a sample of the cases and of the controls was brought in for clinical examinations, psychological testing and computerized EEG. The mean dose delivered to the brain, as determined by dosimetric studies, was 140r and to the thyroid 6-9r. Specific topics to be presented and discussed are as follows: an increased risk of head and neck tumors and the presence of a dose response relationship. The implication of the marked increase in risk for thyroid tumors, in view of the low dose delivered to this organ. Radiation effect on brain function as evidenced by a lower educational achievement, a lower basic intelligence level, somewhat impaired mental ability, and an increased rate of admissions to mental hospitals among cases, as compared to each of the two control groups, as well as the presence of a hyperactivity pattern on EEG

Study on the induction of thyroid tumors in rats using x irradiation in conjunction with a goitrogen

International Nuclear Information System (INIS)

Mahler, P.

1979-01-01

The influence of acute localized thyroid x irradiation and chronic goitrogen administration, separately or combined, on thyroid tumor formation in mature female rats was studied. In the first experiment, the radiation doses were 0, 80, 160, 320, or 640 rads, and the dosages of goitrogen were 0, 4, or 40 parts per million (ppM) of 1 methyl - 2 mercaptoimidazole (MMI). The incidence of rats with thyroid tumors in any treated group receiving 0 or 4 ppM MMI was not significantly greater than the incidence in the nontreated control group. However, the incidence in any of the 40 ppM MMI groups was significantly greater than that in the nontreated control group. At all the radiation doses other than 80 rads, the incidence was significantly greater than that in the non-irradiated group. No significant difference was seen in the incidence of rats with thyroid tumors on the basis of radiation dose. The incidence was so high at 80 rads that there was little margin for further increase by increasing the radiation dose. The mean serum thyroxine levels at 40 ppM MMI, 4 ppM MMI, and 0 ppM MMI were 1.9, 3.5, and 3.7 μg/100 ml, respectively. No markedeffect of thyroid irradiation on mean serum thyroxine levels was seen. In the second experiment, rats receiving 200 ppM MMI and thyroid irradiation were sacrificed at 7-1/2 months after treatment. Nearly all rats in the 0 and 80 rad groups and all in the 160, the 320, and the 640 rad groups had thyroid tumors. In the third experiment, serum T 4 levels were measured in treated rats. Rats receiving 640 rads + 0 ppM MMI showed a slight decrease in serum T 4 , while no change in serum T 4 levels was seen in rats receiving 0 rads + 4 ppM MMI or 640 rads + 4 ppM MMI. All rats receiving 40 ppM MMI, regardless of radiation dose, showed decreased serum T 4 levels

Intraurethral Injection of Autologous Minced Skeletal Muscle

DEFF Research Database (Denmark)

Gräs, Søren; Klarskov, Niels; Lose, Gunnar

2014-01-01

noted. CONCLUSIONS: Intraurethral injection of minced autologous muscle tissue is a simple surgical procedure that appears safe and moderately effective in women with uncomplicated stress urinary incontinence. It compares well to a more complicated regenerative strategy using in vitro expanded muscle......PURPOSE: Intraurethral injection of in vitro expanded autologous skeletal muscle derived cells is a new regenerative therapy for stress urinary incontinence. We examined the efficacy and safety of a simpler alternative strategy using freshly harvested, minced autologous skeletal muscle tissue...... with its inherent content of regenerative cells. MATERIALS AND METHODS: A total of 20 and 15 women with uncomplicated and complicated stress urinary incontinence, respectively, received intraurethral injections of minced autologous skeletal muscle tissue and were followed for 1 year. Efficacy was assessed...

Influence of ICRF-159 and levamisole on the incidence of metastases following local irradiation of a solid tumor

Energy Technology Data Exchange (ETDEWEB)

Baker, D.; Constable, W.; Elkon, D.; Rinehart, L.

1981-11-15

Courses of irradiation consisting of 6000 rad in ten equal fractions over 12 days delivered to KHT sarcomas in mice controlled 55% of the local tumors but 83% of the mice died from metastases. Three strategies to reduce the risk of metastatic spread were tested. The fractionation scheme was changed to deliver the same total dose using a large initial fraction followed by seven equal portions with the same overall time. ICRF-159 was used with the intention of partially synchronizing the tumor growth fraction in a radiosensitive state of the growth cycle and of promoting normalization of the tumor vasculature. Levamisole was used to stimulate the immune system. The combination of ICRF-159 with the eight-fraction radiation course proved to be effective for both increasing local control and decreasing the incidence of metastases. The addition of levamisole did not improve the results obtained with a combination of ICRF-159 and irradiation.

Late health effects of childhood nasopharyngeal radium irradiation: nonmelanoma skin cancers, benign tumors, and hormonal disorders

NARCIS (Netherlands)

Ronckers, Cécile M.; Land, Charles E.; Hayes, Richard B.; Verduijn, Pieter G.; Stovall, Marilyn; van Leeuwen, Flora E.

2002-01-01

Nasopharyngeal radium irradiation (NRI) was widely used from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for benign tumors, nonmelanoma skin cancer, thyroid disorders, and conditions

Irradiation sequels of retinoblastomas

International Nuclear Information System (INIS)

Benk, V.; Habrand, J.L.; Bloch Michel, E.; Soussaline, M.; Sarrazin, D.

1993-01-01

From 1975 to 1985, 34 children with a non-metastatic retinoblastoma were irradiated at the Institut Gustave-Roussy. After enucleation, 19 bilateral tumors were irradiated by two lateral opposed fields and 15 unilateral tumors by one lateral and anterior field, in the case of optic nerve being histologically positive. Dose was 45 Gy, 1.8 Gy per fraction. The 10-year-survival rate for unilateral and bilateral retinoblastomas was 79%. Long term sequels were available for 25 patients: 88% retained one functional eye. Three children with bilateral retinoblastomas developed a cataract in the residual eye between 2 and 5 years after irradiation, none with unilateral tumor. Nine patients (36%), seven with unilateral and two with bilateral tumor developed a cosmetical problem that required multiple surgical rehabilitation between 3 and 14 years after irradiation. Nine children (36%), five with unilateral and four with bilateral tumors developed growth hormone deficit between 2 and 8 years after irradiation that required hormone replacement. Their pituitary gland received 22 to 40 Gy. No osteosarcoma occurred in this population. Among long-term sequels, following irradiation for retinoblastoma, cosmetical deformities represent disabling sequels that could justify new approaches in radiotherapy, as protontherapy combined with 3-D-treatment planning

Spermatogenesis in adult rhesus monkeys following irradiation with X-rays or fission neutrons

International Nuclear Information System (INIS)

Rooij, D.G. de; Sonneveld, P.; Bekkum, D.W. van

A group of male rhesus monkeys was exposed to total body irradiation followed by autologous bone marrow transplantation. The animals were irradiated in the period between 1965 and 1976 and received a dose of 8.5 Gy of X-rays (300 KVP) or 3.6 Gy of 1 MeV fission neutrons. Of this group, a total of 11 male monkeys proved to be evaluable for studying the effects of irradiation on spermatogenesis. (Auth.)

Influence of clinical and tumoral factors on the inter-fractions bones displacements during the treatment of gastric or esophagus cancers by external irradiation

International Nuclear Information System (INIS)

Quivrin, M.; Peignaux, K.; Truc, G.; Blanchard, N.; Ligey-Bartolomeu, A.; Maingon, P.; Crehange, G.; Liegard, M.; Bonnetain, F.; Petitfils, A.

2009-01-01

Purpose: to evaluate the influence of clinical and tumoral characteristics on the inter fractions bones displacements during the irradiation of eso gastric cancers. Conclusion: the local control of irradiated esophagus and gastric cancers stay not satisfying and could be improved by the individual adjustment of peritumoral margins in function of clinical and tumoral characteristics as age, sex, average weight at the beginning of the treatment, the index of the initial average body mass. (N.C.)

No effect of the hemoglobin solution HBOC-201 on the response of the rat R1H tumor to fractionated irradiation

International Nuclear Information System (INIS)

Raabe, A.

2005-01-01

Background and Purpose: Tumor hypoxia is regarded as one important underlying feature of radioresistance. The authors report on an experimental approach to improve tumor response to radiation by combining fractionated irradiation with HBOC-201, an ultrapurified polymerized hemoglobin solution, which is currently used in clinical phase II/III trials as alternative oxygen carrier and proved to be highly effective in tissue oxygenation (tpO 2 ). Material and Methods: Subcutaneously growing rhabdomyosarcoma R1H tumors of the rat were treated with either 40 Gy (2 Gy/fraction, 20 fractions in 2 weeks, ambient) followed by grade top-up doses (clamped) alone, or in combination with HBOC-201, or with HBOC-201 plus carbogen (95% O 2 +5% CO 2 ). Local tumor control (TCD50%) and growth delay were used as endpoints. In addition, the effect of HBOC-201 alone or in combination with carbogen on the tpO 2 of tumor and muscle was determined using a flexible stationary probe (Licox, GMS). Results: TCD50% values of 119 Gy (95% confidence interval 103; 135), 111 Gy (84; 138), and 102 Gy (83; 120) were determined for tumors irradiated alone, in combination with HBOC-201, and with HBOC-201 plus carbogen, respectively. Although the dose-response curves showed a slight shift to lower doses when HBOC-201 or HBOC-201 plus carbogen was added, the differences in TCD50% were not statistically significant. No effect was seen on the growth delay of recurrent tumors. HBOC-201 alone did not effect tumor or muscle tpO 2 . In combination with carbogen the mean tpO 2 muscle raised from 23.9 mmHg to 59.3 mmHg (p 2 by carbogen alone. Conclusion: Low-dose application of HBOC-201 does not improve the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation. (orig.)

Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

International Nuclear Information System (INIS)

Fokas, Emmanouil; Haenze, Joerg; Kamlah, Florentine; Eul, Bastian G.; Lang, Nico; Keil, Boris; Heverhagen, Johannes T.; Engenhart-Cabillic, Rita; An Hanxiang; Rose, Frank

2010-01-01

Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.

Synthesis of Specific Nanoparticles for Targeting and Imaging Tumor Angiogenesis Using Electron-Beam Irradiation

Energy Technology Data Exchange (ETDEWEB)

Rizza, G.; Deshayes, S.; Maurizot, V.; Clochard, M. -C.; Berthelot, T.; Baudin, C.; Déléris, G., E-mail: giancarlo.rizza@polytechnique.edu [Commissariat à l' énergie atomique (CEA), Institut Rayonnement Matière de Saclay (IRaMIS), B.P. 52, 91191 Gif Sur Yvette Cedex (France)

2010-07-01

We have succeeded to synthesize PVDF nanoparticles by nanoemulsion polymerization and their functionalization with a peptide that presents an anti-angiogenic activity. Resulted nanoparticles present a radius of 60 nm. From FESEM images and light scattering measurements, we deduced that they were spherical and monodisperse. The alkyl radicals induced from electron beam irradiation combine immediately with the oxygen to form peroxide radicals. Because of a high specific area and small crystallite size, the radical decay with time is evidenced from EPR measurements. Despite this radical decay, electron beam irradiation allows us to graft PAA by radical polymerization onto freshly irradiated PVDF nanoparticles and then to immobilize CBO-P11 by click chemistry via a spacer arm. Evidences of grafting were shown using HRMAS NMR and MALDI-TOF mass spectrometry. Nanoparticles functionalized with an angiogenesis-targeting agent are an attractive option for anti-tumor therapy.

Synthesis of Specific Nanoparticles for Targeting and Imaging Tumor Angiogenesis Using Electron-Beam Irradiation

International Nuclear Information System (INIS)

Rizza, G.; Deshayes, S.; Maurizot, V.; Clochard, M.-C.; Berthelot, T.; Baudin, C.; Déléris, G.

2010-01-01

We have succeeded to synthesize PVDF nanoparticles by nanoemulsion polymerization and their functionalization with a peptide that presents an anti-angiogenic activity. Resulted nanoparticles present a radius of 60 nm. From FESEM images and light scattering measurements, we deduced that they were spherical and monodisperse. The alkyl radicals induced from electron beam irradiation combine immediately with the oxygen to form peroxide radicals. Because of a high specific area and small crystallite size, the radical decay with time is evidenced from EPR measurements. Despite this radical decay, electron beam irradiation allows us to graft PAA by radical polymerization onto freshly irradiated PVDF nanoparticles and then to immobilize CBO-P11 by click chemistry via a spacer arm. Evidences of grafting were shown using HRMAS NMR and MALDI-TOF mass spectrometry. Nanoparticles functionalized with an angiogenesis-targeting agent are an attractive option for anti-tumor therapy

Tumor induction in mice after local irradiation with single doses of either carbon-ion beams or gamma rays.

Science.gov (United States)

Ando, Koichi; Koike, Sachiko; Ohmachi, Yasushi; Ando, Yutaka; Kobashi, Gen

2014-12-01

To determine the dose-dependent relative biological effectiveness (RBE) for tumor prevalence in mice receiving single localized doses to their right leg of either carbon ions (15, 45 or 75 keV/μm) or 137Cs gamma rays. A total of 1647 female C3H mice were irradiated to their hind legs with a localized dose of either reference gamma rays or 15, 45 or 75 keV/μm carbon-ion beams. Irradiated mice were evaluated for tumors twice a month during their three-year life span, and the dimensions of any tumors found were measured with a caliper. The tumor induction frequency was calculated by Kaplan-Meier analysis. The incidence of tumors from 50 Gy of 45 keV/μm carbon ions was marginally higher than those from 50 Gy of gamma rays. However, 60 Gy of 15 keV/μm carbon ions induced significantly fewer tumors than did gamma rays. RBE values of 0.87 + 0.12, 1.29 + 0.08 or 2.06 + 0.39 for lifetime tumorigenesis were calculated for 15, 45 or 75 keV/μm carbon-ion beams, respectively. Fibrosarcoma predominated, with no Linear Energy Transfer (LET)-dependent differences in the tumor histology. Experiments measuring the late effect of leg skin shrinkage suggested that the carcinogenic damage of 15 keV/μm carbon ions would be less than that of gamma rays. We conclude that patients receiving radiation doses to their normal tissues would face less risk of secondary tumor induction by carbon ions of intermediate LET values compared to equivalent doses of photons.

Harnessing naturally occurring tumor immunity: a clinical vaccine trial in prostate cancer.

Directory of Open Access Journals (Sweden)

Mayu O Frank

2010-09-01

Full Text Available Studies of patients with paraneoplastic neurologic disorders (PND have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC vaccine.We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002, decrease in prostate specific antigen (PSA slope (p = 0.016, and a two-fold increase in PSA doubling time (p = 0.003 were identified when we compared data before and after vaccination.An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine.ClinicalTrials.gov NCT00289341.

Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation

DEFF Research Database (Denmark)

Nielsen, D; Maare, C; Eriksen, J

2001-01-01

PURPOSE: To characterize irradiated murine tumor cells with respect to drug resistance, drug kinetics, and ATPase activity, and to evaluate the possible role of P-glycoprotein (PGP) and murine multidrug resistance associated protein (Mrp1) in the drug-resistant phenotype of these cells. METHODS...... AND MATERIALS: Sensitive Ehrlich ascites tumor cells (EHR2) were in vitro exposed to fractionated irradiation (60 Gy). Western blot analysis was performed for determination of PGP and Mrp1, reverse transcriptase-polymerase chain reaction (RT-PCR) for determination of mdr1a + b mRNA, and semiquantitative RT......-PCR for Mrp1 mRNA. The clonogenic assay was applied to investigate sensitivity, whereas the steady-state drug accumulation of daunorubicin (DNR), 3H-vincristine (VCR), and 3H-etoposide (VP16) was measured by spectrofluorometry and scintillation counting, respectively. For determining of ATPase activity...

Bone marrow transplantation in miniature swine: I. Autologous and SLA matched allografts

International Nuclear Information System (INIS)

Pennington, L.R.; Pescovitz, M.D.; Popitz, F.; Sachs, D.H.; Sakamoto, K.

1986-01-01

We developed a successful bone marrow transplant protocol in MHC-inbred miniature swine (MS). Three groups of MS were studied: irradiation controls, autologous bone marrow transplants and SLA matched bone marrow allografts. One day prior to irradiation, all animals underwent Hickman catheter placement via the external jugular vein. Bone marrow was harvested by direct mechanical removal of marrow from four long bones in Groups 2 and 3 one day prior to irradiation. All animals received 900 rads of midline body radiation from a Cobalt-60 source, were treated 1 g of cephalothin IV bid from day 1 to 14, 20 mg of genetamicin IV bid, from day 4 through 14 and 250 to 350 ml of fresh, irradiated whole blood from blood group identical donors on days 7, 11 and 14. Bone marrow was filtered, washed, stored overnight at 4 C and reinfused one to six hr after irradiation. Engraftment was defined by return of the peripheral WBC to 1000/mm 3 . All six animals in Group 1 died of aplasia between days 7 and 12. Marrow engrafted in eight of 12 animals in Group 2 and 7 of 10 animals in Group 3. This model provides a means to study the biological characteristics of bone marrow transplantation in immunologically well characterized large animals and should prove useful as a model for bone marrow transplants in man

Ultraviolet B irradiation induces expansion of intraepithelial tumor cells in a tissue model of early cancer progression.

Science.gov (United States)

Mudgil, Adarsh V; Segal, Nadav; Andriani, Frank; Wang, Youai; Fusenig, Norbert E; Garlick, Jonathan A

2003-07-01

Ultraviolet B irradiation is thought to enable skin cancer progression as clones of genetically damaged keratinocytes escape apoptosis and expand at the expense of adjacent normal cells. Mechanisms through which potentially malignant cells in human skin undergo clonal expansion, however, are not well understood. The goal of this study was to characterize the role of ultraviolet B irradiation on the intraepithelial expansion of early stage human tumor cells in organotypic skin cultures. To accomplish this, we have studied the effect of ultraviolet B irradiation on organotypic cultures that were fabricated by mixing normal human keratinocytes with beta-galactosidase-marked, intraepithelial tumor cells (HaCaT-ras, clone II-4), which bear mutations in both p53 alleles and harbor an activated H-ras oncogene. We found that when organotypic mixtures were exposed to an ultraviolet B dose of 50 mJ per cm2, intraepithelial tumor cells underwent a significant degree of proliferative expansion compared to nonirradiated cultures. To understand this response, organotypic cultures of nor-mal keratinocytes were exposed to ultraviolet B and showed a dose-dependent increase in numbers of sunburn cells and TUNEL-positive cells although their proliferation was suppressed. In contrast, neither the apoptotic nor the proliferative response of II-4 cells was altered by ultraviolet B in organotypic cultures. The differential response of these cell types suggested that II-4 cells were resistant to ultraviolet-B-induced alterations, which allowed these intraepithelial tumor cells to gain a selective growth and survival advantage relative to neighboring normal cells. These findings demonstrate that ultraviolet B exposure can induce the intraepithelial expansion of apoptosis-resistant, p53-mutant, and ras-activated keratinocytes, suggesting that this agent can act to promote the early stages of epithelial carcinogenesis.

Iatrogenic giant cell tumor at bone graft harvesting site

Directory of Open Access Journals (Sweden)

Zile S Kundu

2013-01-01

Full Text Available 30 year old female patient with giant cell tumor of the distal tibia initially treated at a peripheral nononcological center by curettage and autologous bone grafting from the ipsilateral iliac crest reported to us with local recurrence and an implantation giant cell tumor at the graft harvesting site which required extensive surgeries at both sites. The risk of iatrogenic direct implantation of tumor, often attributable to inadequate surgical planning or poor surgical techniques, and the steps to prevent such complication is reported here.

The influence of ICRF-159 and levamisole on the incidence of metastases following local irradiation of a solid tumor

Energy Technology Data Exchange (ETDEWEB)

Baker, D.; Constable, W.; Elkon, D.; Rinehart, L.

1981-11-15

Courses of irradiation consisting of 6000 rad in ten equal fractions over 12 days delivered to KHT sarcomas in mice controlled 55% of the local tumors but 83% of the mice died from metastases. Three strategies to reduce the risk of metastatic spread were tested. The fractionation scheme was changed to deliver the same total dose using a large initial fraction followed by seven equal portions with the same overall time. ICRF-159 was used with the intention of partially synchronizing the tumor growth fraction in a radiosensitive state of the growth cycle and of promoting normalization of the tumor vasculature. Levamisole was used to stimulate the immune system. The combination of ICRF-159 with the eight-fraction radiation course proved to be effective for both increasing local control and decreasing the incidence of metastases. The addition of levamisole did not improve the results obtained with a combination of ICRF-159 and irradiation.

Studies on the regeneration of the CFU-C population in blood and bone marrow or lethally irradiated dogs after autologous transfusion of cryopreserved mononuclear blood cells

International Nuclear Information System (INIS)

Nothdurft, W.; Bruch, C.; Fliedner, T.M.; Rueber, E.

1977-01-01

In a group of 8 lethally irradiated (1200 R) dogs, that were transfused autologously with cryopreserved mononuclear cells (MNC) derived from the peripheral blood by leucapheresis the concentration of colony-forming units in agar (CFU-C) in bone marrow and peripheral blood was estimated at regular intervals after irradiation and transfusion of MNC. The numbers of MNC transfused per kg body weight ranged from 0.32 x 10 9 to 1.63 x 10 9 with an incidence of CFU-C between 0.02 x 10 5 and 1.38 x 10 5 . In 6 dogs the CFU-C levels in the bone marrow reached the normal preirradiation values between days 15 and 20. But in 2 dogs that had received the lowest CFU-C numbers the regeneration of the bone marrow CFU-C was markedly delayed. In general the time course of the bone marrow repopulation by CFU-C for single dogs was reflected by a corresponding regeneration pattern of the blood CFU-C. The time course of the curves for the blood CFU-C levels on the other hand was of the same kind as for the granulocyte values in the peripheral blood, that reached the normal levels mainly around day 30 and thereafter. Considerable fluctuations were seen in the blood CFU-C levels of single dogs before irradiation and after mononuclear leucocyte transfusion. Despite of such limitations the blood CFU-C content appeared to be a useful indicator of haematopoietic regeneration of the bone marrow. (author)

Possibilities of the reduction of a dose of metronidazole during irradiation of tumor with subsequent induced hyperglycemia

International Nuclear Information System (INIS)

Vinskaya, N.P.; Voloshina, E.A.; Kozin, S.V.

1989-01-01

The therapeutic efficacy of a scheme of polyradiomodification with metronidazole (MZ) administration was investigated in experiments on mice with Ehrlich carcinoma before local irradiation of tumors and with subsequent induced hyperglycemia (IH) depending on a MZ dose. For equally effective potentiation of the effect of radiation on a tumor during a combined use of MZ and postradiation IH a 4-fold lower dose of the drug was required as combined to MZ used alone. The combined effect of the modifiers was superadditive. The use of IH in this scheme not only potentiated skin radiation reactions on a tumor growth zone but also slighly weakened their expression

Progress in radiotherapy of diencephalohypophyseal tumor

Energy Technology Data Exchange (ETDEWEB)

Takakura, Kintomo; Kubo, Osami [Tokyo Women`s Medical Coll. (Japan). Neurological Inst.

1997-12-01

The patients with hypophyseal adenoma (36 patients) were treated with peripheral irradiation (between 10 and 35 Gy) using gamma unit. The results are shown as follows: GH producing hypophyseal tumor (8 patients); tumor volume did not reduce rapidly. Growth hormone level fell, but it took more than 12 months to recover to normal level. PRL producing hypophyseal tumor (5 patients); five intractable patients were irradiated. Tumor contraction was not obvious, but the increase of tumor size was restrained. ACTH producing hypophyseal tumor (4 patients); ACTH level dropped gradually, and tumor size was reduced. However, there were 2 intractable cases. Non-functional hypophyseal tumor (19 patients); local tumor control rate was 100% in all patients and visual field was recovered. The size of craniopharyngioma was obviously reduced with peripheral irradiation of 10 Gy dimension about 10 months later. (K.H.)

Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial.

Science.gov (United States)

Rapp, Stephen R; Case, L Doug; Peiffer, Ann; Naughton, Michelle M; Chan, Michael D; Stieber, Volker W; Moore, Dennis F; Falchuk, Steven C; Piephoff, James V; Edenfield, William J; Giguere, Jeffrey K; Loghin, Monica E; Shaw, Edward G

2015-05-20

Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments. © 2015 by American Society of Clinical Oncology.

Biochemical and immunological alterations of 60 Co irradiated Bothrops jararacussu venom

International Nuclear Information System (INIS)

Spencer, Patrick J.

1995-01-01

Proteins irradiation leads to structural alterations resulting in activity and function loss. This process has been useful to detoxify animal venoms and toxins, resulting in low toxicity products which increased immunogenicity. The Bothrops jararacussu venom behaves as a weak immunogen and its lethal activity in not neutralized by either autologous, heterologous or bothropic polyvalent antisera. This venom is markedly myotoxic and and the commercial bothropic antiserum does not neutralize this activity, because of this low immunogenicity of the myotoxins. This present work was done in order to evaluate the possibility of irradiating Bothrops jararacussu, intending to increase the immunogenicity of the myotoxic components, leading to productions of myotoxins neutralizing antibodies. Bothrops jararacussu venom samples were irradiated with 500, 1000 and 2000 Gy of 60 Co gamma rays. A 2.3 folds decrease of toxicity was observed for the 1000 Gy irradiated samples while the 2000 Gy irradiated sample was at least 3.7 folds attenuated. On the other hand, the 500 Gy did not promote any detoxification. Electrophoresis and HPLC data indicate that the irradiation lead to the formation of high molecular weight products (aggregates). The proteolytic and phospholipasic activities decreased in a dose dependent manner, the phospholipases being more resistant than the proteases. Both the animals (rabbit) immunized with either native or 2000 Gy irradiated venom produced native venom binding antibodies, a slightly higher titer being obtained in the serum of the rabbit immunized with the irradiated samples. Western blot data indicate that the anti-irradiated venom Ig Gs recognised a greater amount of either autologous or heterologous venom bands, both sera behaving as genus specific. The anti-native serum did not neutralize the myotoxic activity of native venom, while the anti-irradiated one was able to neutralize this activity. (author)

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

Science.gov (United States)

Kuranishi, Fumito; Imaoka, Yuki; Sumi, Yuusuke; Uemae, Yoji; Yasuda-Kurihara, Hiroko; Ishihara, Takeshi; Miyazaki, Tsubasa; Ohno, Tadao

2018-01-01

No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988-2002) and in the nationwide population-based cohort study of Denmark (1999-2007). Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

Neurofibrosarcoma at irradiation site in a patient with neurofibromatosis and Wilms' tumor

International Nuclear Information System (INIS)

Chu, J.Y.; O'Connor, D.M.; Danis, R.K.

1981-01-01

A female patient with neurofibromatosis had nephrectomy performed because of Wilms' tumor at the age of four and a half. She received radiation therapy and chemotherapy (actinomycin D) after surgery. She had subsequent local recurrence and lung metastasis, which were surgically excised and successfully treated with additional radiation therapy and chemotherapy (vincristine and actinomycin D). However, neurofibrosarcoma at the irradiation site developed seven years after radiation therapy. She died 22 months later because of recurrence and metastasis of neurofibrosarcoma. Radiation therapy's association with malignant transformation of neurofibroma is discussed

Tumor bed delineation for external beam accelerated partial breast irradiation: A systematic review

International Nuclear Information System (INIS)

Yang, T. Jonathan; Tao, Randa; Elkhuizen, Paula H.M.; Vliet-Vroegindeweij, Corine van; Li, Guang; Powell, Simon N.

2013-01-01

In recent years, accelerated partial breast irradiation (APBI) has been considered an alternative to whole breast irradiation for patients undergoing breast-conserving therapy. APBI delivers higher doses of radiation in fewer fractions to the post-lumpectomy tumor bed with a 1–2 cm margin, targeting the area at the highest risk of local recurrence while sparing normal breast tissue. However, there are inherent challenges in defining accurate target volumes for APBI. Studies have shown that significant interobserver variation exists among radiation oncologists defining the lumpectomy cavity, which raises the question of how to improve the accuracy and consistency in the delineation of tumor bed volumes. The combination of standardized guidelines and surgical clips significantly improves an observer’s ability in delineation, and it is the standard in multiple ongoing external-beam APBI trials. However, questions about the accuracy of the clips to mark the lumpectomy cavity remain, as clips only define a few points at the margin of the cavity. This paper reviews the techniques that have been developed so far to improve target delineation in APBI delivered by conformal external beam radiation therapy, including the use of standardized guidelines, surgical clips or fiducial markers, pre-operative computed tomography imaging, and additional imaging modalities, including magnetic resonance imaging, ultrasound imaging, and positron emission tomography/computed tomography. Alternatives to post-operative APBI, future directions, and clinical recommendations were also discussed

Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

NARCIS (Netherlands)

Meyners, T.; Heisterkamp, C.; Kueter, J.D.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.; Rades, D.

2010-01-01

Background: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from

Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation

International Nuclear Information System (INIS)

Nielsen, Dorte; Maare, Christian; Eriksen, Jens; Litman, Thomas; Skovsgaard, Torben

2001-01-01

Purpose: To characterize irradiated murine tumor cells with respect to drug resistance, drug kinetics, and ATPase activity, and to evaluate the possible role of P-glycoprotein (PGP) and murine multidrug resistance associated protein (Mrp1) in the drug-resistant phenotype of these cells. Methods and Materials: Sensitive Ehrlich ascites tumor cells (EHR2) were in vitro exposed to fractionated irradiation (60 Gy). Western blot analysis was performed for determination of PGP and Mrp1, reverse transcriptase-polymerase chain reaction (RT-PCR) for determination of mdr1a + b mRNA, and semiquantitative RT-PCR for Mrp1 mRNA. The clonogenic assay was applied to investigate sensitivity, whereas the steady-state drug accumulation of daunorubicin (DNR), 3 H-vincristine (VCR), and 3 H-etoposide (VP16) was measured by spectrofluorometry and scintillation counting, respectively. For determining of ATPase activity, the release of inorganic phosphate from ATP was quantified using a colorimetric method. Results: Compared with EHR2, the irradiated cell line EHR2/irr showed increased expression of PGP (threefold), Mrp1 (eightfold), and Mrp1 mRNA (sixfold), and a slight reduction of mdr1b mRNA, whereas mdr1a was present in EHR2 but could not be detected in EHR2/irr. EHR2/irr developed sixfold resistance to VP16, twofold resistance to vincristine, but remained sensitive to DNR. Addition of the PGP inhibitor, verapamil (VER) or depletion of glutathione by buthionine sulfoximine (BSO) partly reversed the resistance in EHR2/irr. In EHR2/irr, the steady-state accumulation of 3 H-VCR and 3 H-VP16 was significantly decreased as compared with EHR2, whereas the accumulation of DNR was unchanged. The ATPase activity of plasma membrane vesicles prepared from EHR2/irr cells was similar to that of wild-type EHR2 cells. The ATPase activity was neither stimulated by vinblastine nor VER. Conclusion: Irradiation induced a multidrug-resistant phenotype in sensitive tumor cells. This phenotype was

One trial treatment for postoperative fistulas of irradiated malignant tumors in the head and neck

International Nuclear Information System (INIS)

Sakai, Noboru; Nagahashi, Tatsumi; Nakamaru, Yuji; Asai, Toshiyuki; Kurihara, Hideo; Katoh, Akio; Yokohama, Masaki; Gotohda, Hiroyuki; Inuyama, Yukio

1995-01-01

It is very difficult to treat postoperative fistulas of irradiated malignant tumors in the head and neck. These fistulas generally require either surgical or conservative therapy, but the poor healing induced by irradiation means that a long time is required to obtain a complete cure. As one of the conservative therapies for these wounds, we first applied alcloxa powder which had been used as the treatment of either decubitis or ulcers, and we thus were able to obtain a complete cure in 8 patients without the need for any reconstructive surgery. The number of days required to obtain a complete cure of the fistulas ranged from 9 to 84 days, with an average of 39.8 days. These results indicated that this powder had an excellent efficacy on wound healing, and it should thus be used frequently on incurable postoperative fistulas after irradiation in head and neck malignancies. (author)

One trial treatment for postoperative fistulas of irradiated malignant tumors in the head and neck

Energy Technology Data Exchange (ETDEWEB)

Sakai, Noboru; Nagahashi, Tatsumi; Nakamaru, Yuji; Asai, Toshiyuki; Kurihara, Hideo; Katoh, Akio; Yokohama, Masaki; Gotohda, Hiroyuki; Inuyama, Yukio [Hokkaido Univ., Sapporo (Japan). School of Medicine

1995-03-01

It is very difficult to treat postoperative fistulas of irradiated malignant tumors in the head and neck. These fistulas generally require either surgical or conservative therapy, but the poor healing induced by irradiation means that a long time is required to obtain a complete cure. As one of the conservative therapies for these wounds, we first applied alcloxa powder which had been used as the treatment of either decubitis or ulcers, and we thus were able to obtain a complete cure in 8 patients without the need for any reconstructive surgery. The number of days required to obtain a complete cure of the fistulas ranged from 9 to 84 days, with an average of 39.8 days. These results indicated that this powder had an excellent efficacy on wound healing, and it should thus be used frequently on incurable postoperative fistulas after irradiation in head and neck malignancies. (author).

Irradiation of the testes in radiotherapy of Hodgkin's disease and testicular tumors

International Nuclear Information System (INIS)

Bakyrdzhiev, S.; Ganchev, M.; Milchev, V.; Naumova, Ts.

1983-01-01

Direct measurements using TLD dosimeters permitted to calculate radiation doses delivered to the testes in radiotherapy for supradiaphragmatic forms of Hodgkin's disease, stages I and II; they were found to constitute from 1 to 2% of focal dose, that is, to amount to 40-80 cGy given in 20 nonuniform fractions. In radiotherapy for subdiaphragmatic forms of the disease, the dose to the testes varied from 360 to 400 cGy. Anthropomorphic, phantom measurements with ionization chambers placed within the phantom testes showed contributions to total testicular dose to vary with individual irradiation fields in these cases. Thus, for instance, 82% of total dose was due to irradiation of both iliac fields; shielding of the testes with lead caps (5mm) reduced this irradiation to one-half. Doses to the testes were relatively large in radiotherapy for testicular tumors (seminomas and teratocarcinomas). By combining radiotherapy with chemotherapy or surgical intervention, permanent cure or long-lasting remissions may be achieved in most cases. In this connection, there arises the question as to the potential risk of patients - mostly young males with maintained reproductive capacity - transmitting radiation - induced genetic damage to their progeny. An attempt was made to appraise such genetic risk from additional above-background exposure. (authors)

Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

NARCIS (Netherlands)

Meyners, Thekla; Heisterkamp, Christine; Kueter, Jan-Dirk; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.; Rades, Dirk

2010-01-01

This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the

Systematization of the Mechanism by Which Plasma Irradiation Causes Cell Growth and Tumor Cell Death

Science.gov (United States)

Shimizu, Nobuyuki

2015-09-01

New methods and technologies have improved minimally invasive surgical treatment and saved numerous patients. Recently, plasma irradiation has been demonstrated that might be useful in medical field and the plasma irradiation device is expected to become practically applicable. Mild plasma coagulator showed some advantages such as hemostasis and adhesion reduction in experimental animal model, but the mechanism of plasma irradiation remains unclear. Our study group aim to clarify the mechanism of plasma irradiation effects, mainly focusing on oxidative stress using cultured cell lines and small animal model. First, a study using cultured cell lines showed that the culture medium that was activated by plasma irradiation (we called this kind of medium as ``PAM'' -plasma activated medium-) induced tumor cell death. Although this effect was mainly found to be due to hydrogen peroxide, the remaining portion was considered as the specific effect of the plasma irradiation and we are now studying focusing on this effect. Second, we established a mouse intra-peritoneal adhesion model and checked biological reaction that occurred in the adhesion part. Histopathological study showed inflammatory cells infiltration into adhesion part and the expression of PTX3 that might involve tissue repair around adhesion part. We also confirmed that cytokines IL-6 and IL-10 might be useful as a marker of adhesion formation in this model. Applying ``PAM'' or mild plasma irradiation in this model, we examine the effects of plasma on inflamed cells. The samples in these experiments would be applied to targeted proteomics analysis, and we aim to demonstrate the systematization of the cell's reaction by plasma irradiation.

Chimeric autologous/allogeneic constructs for skin regeneration.

Science.gov (United States)

Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn

2014-08-01

The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Relative Biologic Effectiveness (RBE) of 50 kV X-rays Measured in a Phantom for Intraoperative Tumor-Bed Irradiation

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Liu, Qi; Schneider, Frank; Ma, Lin; Wenz, Frederik [Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany); Herskind, Carsten, E-mail: carsten.herskind@medma.uni-heidelberg.de [Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany)

2013-03-15

Purpose: Intraoperative radiation therapy (IORT) with low-energy x-rays is used to treat the tumor bed during breast-conserving surgery. The purpose was to determine the relative biologic effectiveness (RBE) of 50-kV x-rays for inactivation of cells irradiated in a tumor-bed phantom. Methods and Materials: The RBE was determined for clonogenic inactivation of human tumor and normal cells (MCF7, human umbilical vein endothelial cells, normal skin fibroblasts), and hamster V79 cells. The 50-kV x-rays from the Intrabeam machine (Carl Zeiss Surgical) with a spherical 4-cm applicator were used. Cells were irradiated in a water-equivalent phantom at defined distances (8.1-22.9 mm) from the applicator surface. The 50-kV x-rays from a surface therapy machine (Dermopan, Siemens) were included for comparison; 6-MV x-rays were used as reference radiation. Results: At 8.1-mm depth in the phantom (dose rate 15.1 Gy/h), mean RBE values of 50-kV x-rays from Intrabeam were 1.26 to 1.42 for the 4 cell types at doses yielding surviving fractions in the range of 0.01 to 0.5. Confidence intervals were in the range of 1.2 and 1.5. Similar RBE values were found for 50-kV x-rays from Dermopan for V79 (1.30, CI 1.25-1.36, P=.74) and GS4 (1.42, CI 1.30-1.54, P=.67). No significant dependence of RBE on dose was found for Intrabeam, but RBE decreased at a larger distance (12.7 mm; 9.8 Gy/h). Conclusions: An increased clinically relevant RBE was found for cell irradiation with Intrabeam at depths in the tumor bed targeted by IORT. The reduced RBE values at larger distances may be related to increased repair of sublethal damage during protracted irradiation or to hardening of the photon beam energy.

Anti-tumor effect of low dose radiation in mice

International Nuclear Information System (INIS)

Fan Zhengping; Lu Jiaben; Zhu Bingchai

1997-01-01

The author reports the effects of the total body irradiation of low dose radiation (LDR) and/or the local irradiation of large dose on average tumor weights and tumor inhibitory rates in 170 mice inoculated S 180 sarcoma cell, and the influence of LDR on average longevity in 40 tumor-bearing animals. Results show (1) LDR in the range of 75∼250 mGy can inhibit tumor growth to some extent; (2) fractionated irradiation of 75 mGy and local irradiation of 10 Gy may produce a synergism in tumor growth inhibition; and (3)LDR may enhance average longevity in ascitic tumor-bearing mice

Stereotaxic external irradiation for brain tumors

International Nuclear Information System (INIS)

Kim, Y.H.; Fayos, J.V.; Houdek, P.V.; Landy, H.; Van Buren, J.

1987-01-01

A system has been developed to deliver precision radiation therapy to a limited volume of brain tissue. A CT-compatible nonmetallic headband, or ''halo,'' is secured to the skull with screw pins. A metal frame attached to the CT couch and the patient's head is secured to the couch by temporarily affixing the halo to the frame. A CT scan is obtained to determine the x,y,z coordinates of the brain lesion. The same halo, frame, and coordinates are used in daily treatment with 10-MVX accelerator and a coplanar arc rotation technique. Field size is determined to cover the target volume with the 90% isodose line. Verification films are obtained twice a week. On completion of treatment, the halo is removed. From December 1982 to January 1986, 14 patients were treated with this system. Six had pituitary tumors, two had craniopharyngiomas, and six had astrocytomas. The dose delivered ranged from 3,600 rad in 12 fractions to 6,250 rad in 25 fractions at a rate of one fraction per day, 5 days a week. Judging from the verification films, daily administration of intended radiation was extremely good. Superficial infection of the screw-pin sites healed without sequelae. All patients were alive at the last follow-up. This system is relatively simple yet able to deliver precision irradiation without any remarkable complications

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 7

International Nuclear Information System (INIS)

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

1983-01-01

We have already reported the remarkable effect of the active specific immunotherapy utilizing cryopreserved tumor cells and infiltrating mononuclear cells prepared from a lowdose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, PSK combined with this active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor cells were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the fifth day after tumor inoculation. This active specific immunotherapy was performed on the twelveth day, and daily dose of 200 mg/kg of PSK was injected intraperitoneally from the sixth day to the tenth day. The more inhibition of the tumor growth was observed in the group which received this active specific immunotherapy combined with a biological response modifier, PSK compared with that received this active specific immunotherapy alone. (author)

Enhancement of tumor cell killing in vitro by pre- and post-irradiation exposure to aclacinomycin A

International Nuclear Information System (INIS)

Bill, C.A.; Mendoza, A.; Vrdoljak, E.; Tofilon, P.J.

1993-01-01

Aclacinomycin A (ACM), a potent inducer of leukemic cell differentiation, significantly enhances the radiosensitivity of a human colon tumor cell line (Clone A) when cultures are exposed to 15-nM concentrations for 3 days before irradiation. We now demonstrate that incubation with ACM after irradiation can also enhance Clone A cell killing. The maximum increase in cell killing, based on colony-forming ability, occurred when Clone A cells were exposed for 1 h to 5 μM ACM model added 1 or 2 h after irradiation. The post-irradiation ACM protocol reduced the terminal slope (as reflected by D o ) of the radiation cell survival curve with no change in the low-dose, shoulder region of the curve (D q value). In contrast, for pre-irradiation treatment with ACM (15 nM, 3 days), the shoulder region of the curve was reduced with no change in the terminal slope. For pre- and post-irradiation ACM treatment the dose enhancement factors at 0.10 survival were 1.22 and 1.28, respectively. When ACM was given both before and after irradiation both the shoulder and terminal slope values decreased to produce a dose enhancement factor at a surviving fraction of 0.10 of 1.50. These data suggest that the enhanced cell killing produced by pre- and post-irradiation treatment with ACM is achieved through different mechanisms. (author) 26 refs., 3 tabs., 2 figs

Effects of x-irradiation of young female beagles on life span and tumor incidence

International Nuclear Information System (INIS)

Rosenblatt, L.S.; Book, S.A.; Goldman, M.

1986-01-01

Causes of death and the occurrence of neoplasia in female beagle dogs were evaluated retrospectively for 57 unexposed and 296 exposed dogs given single or fractionated whole-body x-irradiation exposures of 100 or 300 R. Some dogs subsequently were bred, and all were observed for the duration of their lives. The pathology for these dogs was derived from clinical records, gross-necropsy reports, tissue slides, and Formalin-fixed tissues. The results of this study indicated dose-related shortening of life span was clearly evident; causes of death due to either neoplasia (50%) or nonneoplastic disease (50%), with few exceptions, were similar in control and irradiated dogs; the incidences of neoplasms were not significantly greater for irradiated dogs than for controls, but the latency period decreased as dose increased; protraction increased survival in dogs given 300 R but not 100 R, which is attributable solely to amelioration of incidence rates of nonmammary neoplasia; and the cumulative rates of death due to mammary tumors were the same in dogs exposed to 100 R and 300 R. 14 refs., 6 figs., 2 tabs

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 8

International Nuclear Information System (INIS)

Imanaka, Kazufumi; Gose, Kyuhei; Ichiyanagi, Akihiro

1983-01-01

The effectiveness of active specific immunotherapy prepared from a low-dose irradiated tumor tissue has already reported. The present study was designed to investigate the effect of Mitomycin C-treated active specific immunotherapy. Twelve-week-aged female C3H/He mice transplanted with MM 46 tumors were exposed to local electron radiotherapy with a dose of 3,000 rad on the 5th day after tumor inoculation. Tumor cells prepared for active specific immunotherapy were pretreated with Mitomycin C at concentration of 20 μg/10 7 cells in Eagle MEM Earle containing 100 IU/ml penicillin. The cell suspension was incubated at 37 0 C for 15 minutes. Mitomycin C-treated active specific immunotherapy was performed on the 12th day. Antitumor effect was evaluated by the regression of the tumor and survival curve. The remarkable regression of the tumor and significant elongation of the survival period were observed in the group which received Mitomycin C-treated active specific immunotherapy and the group which received active specific immunotherapy without the treatment of Mitomycin C. (author)

Cross-immunity among mammary carcinomas in C3H/HE mice immunized with gamma-irradiated tumor cells

International Nuclear Information System (INIS)

Waga, Takashi

1980-01-01

By immunization with gamma-irradiated (13,000 rad) tumor cells, cross-immunity between ascites mammary carcinomas and among solid mammary carcinomas in C3H/He mice was studied. The results were as follows: (1) Two ascites mammary carcinomas designated MM 46 (high vitality) and MM 48 (intermediate vitality) were used in this experiment. The immunization with the tumor of high vitality (MM 46) induced strong cross-immunity against the challenge of the tumor of intermediate vitality (MM 48). The immunization with the tumor of intermediate vitality (MM 48) induced weak cross-immunity against the challenge of the tumor of high vitality (MM 46). (2) Three solid mammary carcinomas designated MT 10 (intermediate vitality), MT 7 (high vitality) and MT X (the highest vitality) were used in this experiment. The immunization with the tumor of high vitality (MT 7) induced strong cross-immunity against the challenge of the tumor of intermediate vitality (MT 10), and induced moderate cross-immunity against the challenge of the tumor of the highest vitality (MT X). The immunization with the tumor of intermediate vitality (MT 10) induced moderate cross-immunity against the challenge of the tumor of high vitality (MT 7), but could not induce any cross-immunity against the challenge of the tumor of the highest vitality (MT X). (author)

Cell-mediated immunity in operable bronchial carcinoma: the effect of injecting irradiated autologous tumour cells and BCG

International Nuclear Information System (INIS)

Stack, B.H.R.; McSwan, N.; Stirling, J.M.

1979-01-01

In 52 patients undergoing tests of cell-mediated immunity before surgical resection of bronchial carcinoma a positive tuberculin test result was found in 71% compared with 68% of age - and sex-matched controls. Sensitization to DNCB occurred in 52% of 37 patients but in 78% controls. There was depression of lymphocyte transformation by PPD in 19 patients compared with controls (p=0.001), but there was no difference in lymphocyte transformation by PHA pr pokeweed mitogen between 34 patients and controls. In a pilot study patients were randomly allocated to autograft (eight) or non-autograft (seven) groups. The autograft group were given an intradermal injection of a suspension of irradiated autologous tumour-cells mixed with intradermal BCG on the day of operation. Tests of cell-mediated immunity were repeated two weeks after operation. Five patients in each group received a course of radiotherapy to the mediastinum three weeks after operation. There was a rise in a cutaneous tuberculin reactivity (p=0.08) and total leucocyte count (p=0.09) in the autograft group postoperatively with a fall in total lymphocyte and T lymphocyte counts in the non-autograft group (p<0.05). These differences, however, were not followed by any difference in the frequency of tumour recurrence or the survival rate two years after operation. The results show that the immunological surveillance mechanism is impaired even in patients with early bronchial carcinoma and that it is possible to overcome postoperative immunological depression with specific immunotherapy combined with BCG. This treatment did not produce any clinical advantage in this small number of patients and the skin lesions caused the patients considerable discomfort. (author)

Dosimetric investigation depending on tumor location in patient breast in partial breast irradiation

International Nuclear Information System (INIS)

Kim, Min Joo; Park, So Hyun; Jung, Joo Young; Woong, Cho; Suh, Tae Suk

2012-01-01

The Partial Breast Irradiation (PBI) technique, which involves radiation beam delivery techniques that use a limited range of treatment volumes, has been a challenging approach that is worthy of consideration compared to whole-breast radiation therapy (WBRT). Because of a small target volumes used in the PBI technique, the radiation dose can be safely delivered to the targeted tissue without the unwanted delivery of radiation to normal breast tissues and organ at risk (OAR), such as contralateral breast, lung and heart.Through PBI technique, better cosmetic outcomes and minimizing damages to OARs could be expected and also the daily dose can be increased with smaller number of fractionation in radiation therapy. The purpose of this study was to evaluate the dosimetric effects according to tumor locations in patient's breast for Partial Breast Irradiation (PBI) technique using three Dimensional Conformal Radiation Therapy (3DCRT), Electron Beam Radiation therapy (EBRT) and Helical-tomotherapy (H-TOMO). Dosimetric comparisons of PBI technique for 3DCRT, EBRT, and H-TOMO depending on the classified tumor locations were performed. H-TOMO delivered the low dose to lager volume to surrounding normal tissue, such as the heart and lungs compared to 3DCRT and EBRT although it had the same degree of target coverage as the other methods (3DCRT, EBRT). EBRT had a curative effect for early-stage breast cancers located in the lower and inner sections (LIQ-S, LIQ-D)

Treatment of blastic transformation of chronic granulocytic leukemia by chemotherapy, total body irradiation and infusion of cryopreserved autologous marrow

Energy Technology Data Exchange (ETDEWEB)

Buckner, C D; Stewart, P; Clift, R A; Fefer, A; Neiman, P E; Singer, J; Storb, R; Thomas, E D [Washington Univ., Seattle (USA). School of Medicine; The United States Public Health Service Hospital; Providence Medical Center, and the Fred Hutchinson Cancer Research Center, Seattle, Washington, USA)

1978-01-01

We have previously reported attempts to reestablish the chronic phase of chronic granulocytic leukemia (CGL), in two patients with blastic transrormation, utilizing intensive therapy followed by the infusion of cryopreserved autologous marrow. This approach has now been attempted in a total of seven patients. Marrow was harvested on single or multiple occasions during the chronic phase of CGL and cryopreserved in 10% dimethylsulfoxide. All patients were treated with cyclophosphamide, 120 mg/kg, plus 1,000 rad of total body irradiation followed by infusion of stored marrow. Two patients failed to achieve marrow repopulation and died of infection after 29 and 48 days. Three patients had partial marrow recovery. Two of these achieved repopulation of myeloid, erythroid, and lymphoid elements but did not recover platelet function; one died of hemorrhage on day 55, and one died of cytomegalovirus interstitial pneumonitis on day 58. A third patient had delayed engraftment of all cell elements, most prominently lymphocytes, and died after 84 days of an iodopathic interstitial pneumonitis. Two patients achieved prompt and complete reestablishment of the chronic phase of CGL. One died on day 72 with a fungal pheumonitis and one developed blastic transformation within 4 months. These preliminary results indicate that this approach to the treatment of blastic transformation of CGL is feasible but difficult. Improvements in results may be achieved by more frequent storage of marrow and pheripheral blood stem cells and lymphocytes and further advances in pretransplant therapy.

Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

International Nuclear Information System (INIS)

Bourke, Vincent A.; Zhao Dawen; Gilio, Joseph; Chang, C.-H.; Jiang Lan; Hahn, Eric W.; Mason, Ralph P.

2007-01-01

Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by 19 F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm 3 ) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO 2 ) than their smaller counterparts ( 3 ). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO 2 , and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO 2 > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy

Predeposit autologous blood transfusion: Do we require to promote it?

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Gurjit Singh

2015-01-01

Full Text Available Introduction: Safest blood a patient can receive is his own. Quest for safe blood transfusion has remained of prime concern. To meet this aspiration, various forms of autologous blood transfusions can be practiced. It is especially suitable for patients with rare blood groups and religious sects such as Jehovah′s witness autologous transfusion is extremely safe. Cross matching is not required; iso-immunization to a foreign body is excluded. Fear of transfusion transmissible disease can be ignored. Therefore, autologous blood transfusion is required to be revisited. Materials and Methods: This is a prospective study carried out at Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune between July 2010 and May 2012. Study comprised of 100 patients divided into two groups, autologous and homologous. Benefits of autologous transfusion were studied. Results: There was no significant change in hematocrit and blood parameters after blood donation. That is mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (P < 0.001 after blood donation. Only one complication of vasovagal syncope was observed at the time of blood donation. Conclusion: Autologous blood transfusion is safe. Easy alternative to be practiced in elective surgeries, especially in patients with rare blood group or believers of Jehovah′s witness faith. It helps to reduce the shortfall in national blood inventory. Autologous blood donation should be practiced whenever possible.

Subclinical hypothyroidism in children and adolescents after hematopoietic stem cells transplantation without irradiation

Directory of Open Access Journals (Sweden)

Milenković Tatjana

2014-01-01

Full Text Available Background/Aim. Although total body irradiation (TBI was considered to be the primary cause of thyroid dysfunction following hematopoietic stem cells transplantation (HSCT, a significant prevalence of subclinical hypothyroidism after HSCT with chemotherapy-only conditioning regimens has been observed in several studies. The aim of this study was to assess changes in thyroid stimulating hormone (TSH levels in children after HSCT, without the use of irradiation at any time in the course of the treatment. Methods. Our cohort consisted of 41 children and adolescents who underwent autologous or allogeneic HSCT and were available for follow-up for at least one year after transplantation. Irradiation was not performed in any of the subjects, neither during pretransplatation therapy, nor during conditioning. The median duration of follow-up was 2.9 years. The indications for HSCT were hematologic malignancy (41.5%, solid malignant tumor (34.1%, and other disorders (24.4%. The thyroid status of all the subjects was assessed prior to HSCT and after follow-up period. Results. Thyroid dysfunction after HSCT was present in 27 (65.8% subjects. Subclinical hypothyroidism was the most common abnormality, presenting in 23 (56.1% patients, primary hypothyroidism was present in one (2.4% patient, while 3 (7.3% subjects had low free T4 with normal TSH values. Significantly (p < 0.01 higher elevations in TSH levels were present in the patients who received chemotherapy for the underlying disease prior to HSCT. Conclusion. Our findings emphasize the need for long-term monitoring of thyroid function following HSCT, regardless of whether or not irradiation was used.

Pathogenesis of Cognitive Decline Following Therapeutic Irradiation for Head and Neck Tumors

International Nuclear Information System (INIS)

Abayomi, Olubunmi K.

2002-01-01

Cognitive decline is a significant but largely unrecognized sequela following irradiation for several head and neck tumors, particularly cancer of the nasopharynx and paranasal sinuses. In this article the cellular mechanisms of radiation-induced vascular damage in the temporal lobe and its effects on the medial temporal lobe memory systems are described. Recognition of the mechanisms and site of the injury should permit the use of treatment planning systems, such as 3-dimensional (3-D) conformal and intensity-modulated radiotherapy (IMRT) techniques, to spare large volumes of the temporal lobe from receiving a high dose. Furthermore, the emerging concepts of vascular irradiation damage as an inflammatory fibroproliferative response to endothelial injury may permit the application of measures directed at inhibiting the expression of proinflammatory genes and thus mitigate the inflammatory response. Moreover, comorbid factors such as hypertension, diabetes, lipidemia, obesity and smoking are known to promote atherogenesis and therefore may exacerbate radiation-induced vascular damage. Control of these factors may also reduce the incidence and severity of this sequela

Effects of X-irradiation on artificial blood vessel wall degradation by invasive tumor cells

International Nuclear Information System (INIS)

Heisel, M.A.; Laug, W.E.; Stowe, S.M.; Jones, P.A.

1984-01-01

Artificial vessel wall cultures, constructed by growing arterial endothelial cells on preformed layers of rat smooth muscle cells, were used to evaluate the effects of X-irradiation on tumor cell-induced tissue degradation. Bovine endothelial cells had radiation sensitivities similar to those of rat smooth muscle cells. Preirradiation of smooth muscle cells, before the addition of human fibrosarcoma (HT 1080) cells, did not increase the rate of degradation and destruction by the invasive cells. However, the degradation rate was decreased if the cultures were irradiated after the addition of HT 1080 cells. The presence of bovine endothelial cells markedly inhibited the destructive abilities of fibrosarcoma cells, but preirradiation of artificial vessel walls substantially decreased their capabilities to resist HT 1080-induced lysis. These findings suggest that the abilities of blood vessels to limit extravasation may be compromised by ionizing radiation

Radiation effects on tumor-specific DTH response, 2

International Nuclear Information System (INIS)

Nobusawa, Hiroshi; Hachisu, Reiko.

1991-01-01

Tumor-specific immunity was induced in C3H mice by immunizing with syngeneic MH134 hepatoma cells. Radiation sensitivity of anti-tumor activity of immunized spleen cells were examined and compared with the radiation sensitivity of the delayed-type hypersensitivity (DTH)-response. The spleen cells were irradiated in vitro, then mixed with the tumor cells. DTH-response intensity was determined from the footpad increment twenty-four hours after inoculation of tumor cells with immunized spleen cells. Anti-tumor activity of the spleen cells, based on growth inhibition of tumor cells, was measured by a cytostatic test in vivo with diffusion chambers. Tumor-specific DTH response was suppressed dose-dependently in the range of 12-24 Gy irradiation. No suppression was observed below 12 Gy. Without irradiation, growth of tumor cells was inhibited by immunized spleen cells more effectively than by normal spleen cells. Anti-tumor activity of immunized and normal spleen cells was diminished by irradiation doses of 20 Gy and 10 Gy, respectively. Comparing our report with others that analyzed the type of anti-tumor effector cells induced in this experimental system, we concluded that tumor-specific anti-tumor activity (tumor growth inhibition in vivo) that was radiosensitive at 10-20 Gy depended on a DTH-response. (author)

Carbon Ion irradiation in the treatment of grossly incomplete or unresectable malignant peripheral nerve sheaths tumors: acute toxicity and preliminary outcome

International Nuclear Information System (INIS)

Jensen, Alexandra D; Uhl, Matthias; Chaudhri, Naved; Herfarth, Klaus K; Debus, Juergen; Roeder, Falk

2015-01-01

To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST). We retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts). Median follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays). Carbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial

Transplantation of autologous bone marrow in three patients with acute myelogenous leukaemia during the first remission

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Loewenberg, B; Sizoo, W; Sintnicolaas, K; Hendriks, W D.H.; Poel, J van der [Rotterdams Radio Therapeutisch Inst. (Netherlands); Abels, J; Dzoljic, G [Akademisch Ziekenhuis Rotterdam-Dijkzigt (Netherlands); Bekkum, D.W. van; Wagemaker, G [Gezondheidsorganisatie TNO, Rijswijk (Netherlands). Radiobiologisch Inst. TNO

1983-07-23

A report is presented on the first results of transplantation of autologous bone marrow in 3 adult patients with acute myelogenous leukaemia. The treatment consisted of intensive chemotherapy and whole-body irradiation and was followed by transplantation of a limited number of non-purified bone-marrow cells that had previously been collected from the patient. In all three patients, transplantation was followed by a stable remission. One patient had a fatal recurrence after a total period of 21 months of remission. In 2 patients, the remissions continue. The clinical significance of these findings is discussed.

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine

Directory of Open Access Journals (Sweden)

Fumito Kuranishi

2018-01-01

Full Text Available Introduction. No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV. Patients and Methods. AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20 after comprehensive treatments including AFTV. The median overall survival time (60.0 months and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988–2002 and in the nationwide population-based cohort study of Denmark (1999–2007. Conclusion. Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

Cytokine-primed bone marrow stem cells vs. peripheral blood stem cells for autologous transplantation: a randomized comparison of GM-CSF vs. G-CSF.

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Weisdorf, D; Miller, J; Verfaillie, C; Burns, L; Wagner, J; Blazar, B; Davies, S; Miller, W; Hannan, P; Steinbuch, M; Ramsay, N; McGlave, P

1997-10-01

Autologous transplantation for non-Hodgkins lymphoma and Hodgkin's disease is widely used as standard therapy for those with high-risk or relapsed tumor. Peripheral blood stem cell (PBSC) collections have nearly completely replaced bone marrow stem cell (BMSC) harvests because of the perceived advantages of more rapid engraftment, less tumor contamination in the inoculum, and better survival after therapy. The advantage of PBSC, however, may derive from the hematopoietic stimulating cytokines used for PBSC mobilization. Therefore, we tested a randomized comparison of GM-CSF vs. G-CSF used to prime either BMSC or PBSC before collection for use in autologous transplantation. Sixty-two patients receiving transplants (31 PBSC; 31 BMSC) for non-Hodgkin's lymphoma (n = 51) or Hodgkin's disease (n = 11) were treated. All patients received 6 days of randomly assigned cytokine. Those with cellular marrow in morphologic remission underwent BMSC harvest, while those with hypocellular marrow or microscopic marrow tumor involvement had PBSC collected. Neutrophil recovery was similarly rapid in all groups (median 14 days; range 10-23 days), though two patients had delayed neutrophil recovery using GM-CSF primed PBSC (p = 0.01). Red cell and platelet recovery were significantly quicker after BMSC mobilized with GM-CSF or PBSC mobilized with G-CSF. This speedier hematologic recovery resulted in earlier hospital discharge as well. However, in multivariate analysis, neither the stem cell source nor randomly assigned G-CSF vs. GM-CSF was independently associated with earlier multilineage hematologic recovery or shorter hospital stay. Relapse-free survival was not independently affected by either the assigned stem cell source or the randomly assigned priming cytokine, though malignant relapse was more frequent in those assigned to PBSC (RR of relapse 3.15, p = 0.03). These data document that BMSC, when collected following cytokine priming, can yield a similarly rapid hematologic

Tumor control probability after a radiation of animal tumors

International Nuclear Information System (INIS)

Urano, Muneyasu; Ando, Koichi; Koike, Sachiko; Nesumi, Naofumi

1975-01-01

Tumor control and regrowth probability of animal tumors irradiated with a single x-ray dose were determined, using a spontaneous C3H mouse mammary carcinoma. Cellular radiation sensitivity of tumor cells and tumor control probability of the tumor were examined by the TD 50 and TCD 50 assays respectively. Tumor growth kinetics were measured by counting the percentage of labelled mitosis and by measuring the growth curve. A mathematical analysis of tumor control probability was made from these results. A formula proposed, accounted for cell population kinetics or division probability model, cell sensitivity to radiation and number of tumor cells. (auth.)

Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor

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Bourke, Vincent A [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Dawen, Zhao [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Gilio, Joseph [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Chang, C -H [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Lan, Jiang [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Hahn, Eric W [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States); Mason, Ralph P [Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX (United States)

2007-03-15

Purpose: To investigate the application of pretreatment oxygenation to the AT1 subline of the Dunning R3327 prostate tumor, which is more hypoxic and faster growing than the H1 subline previously studied. Methods and Materials: Dunning prostate R3327-AT1 tumors growing on Copenhagen rats were administered 30 Gy of X-ray radiation either with or without oxygen inhalation. Tumor oxygenation was sampled by {sup 19}F nuclear magnetic resonance echo planar imaging relaxometry of the reporter molecule hexafluorobenzene, no more than 24 h before irradiation. Results: Large tumors (>3.0 cm{sup 3}) exhibited significantly greater hypoxic fractions and lower mean partial pressure of oxygen (pO{sub 2}) than their smaller counterparts (<1.5 cm{sup 3}). However, unlike the R3327-HI subline, large AT1 tumors generally did not respond to oxygen inhalation in terms of altered hypoxic fraction or response to irradiation. Although the tumors did not respond to oxygen inhalation, each tumor had a different pO{sub 2}, and there was a clear trend between level of oxygenation at time of irradiation and tumor growth delay, with considerably better outcome when mean pO{sub 2} > 10 mm Hg. The comparatively small baseline hypoxic fraction in the group of small tumors was virtually eliminated by breathing oxygen, and the growth rate was significantly reduced for tumors on rats breathing oxygen during irradiation. Conclusions: These results further validate the usefulness of nuclear magnetic resonance oximetry as a predictor of response to radiation therapy.

Intracranial meningiomas after high-dose irradiation

International Nuclear Information System (INIS)

Soffer, D.; Gomori, J.M.; Siegal, T.; Shalit, M.N.

1989-01-01

Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with ''spontaneous'' meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.41 references

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 5

International Nuclear Information System (INIS)

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

1982-01-01

We have already reported the remarkable effect of the active specific immunotherapy utilizing cryopreserved tumor cells and infiltrating mononuclear cells prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, OK-432 combined with this active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor cells were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the sixth day after inoculation. This active specific immunotherapy was performed on the thirteenth day, and daily dose of 1.0 KE of OK-432 was injected intraperitoneally from the thirteenth day to the seventeenth day. The inhibition of the tumor growth was observed in the group which received this active specific immunotherapy combined with a biological response modifier, OK-432 compared with that received this active specific immunotherapy alone. (author)

Feasibility of Helical Tomotherapy for Debulking Irradiation Before Stem Cell Transplantation in Malignant Lymphoma

International Nuclear Information System (INIS)

Chargari, Cyrus; Vernant, Jean-Paul; Tamburini, Jerome; Zefkili, Sofia; Fayolle, Maryse; Campana, Francois; Fourquet, Alain; Kirova, Youlia M.

2011-01-01

Purpose: Preliminary clinical experience has suggested that radiation therapy (RT) may be effectively incorporated into conditioning therapy before transplant for patients with refractory/relapsed malignant lymphoma. We investigated the feasibility of debulking selective lymph node irradiation before autologous and/or allogeneic stem cell transplantation (SCT) using helical tomotherapy (HT). Methods and Materials: Six consecutive patients with refractory malignant lymphoma were referred to our institution for salvage HT before SCT. All patients had been previously heavily treated but had bulky residual tumor despite chemotherapy (CT) intensification. Two patients had received previous radiation therapy. HT delivered 30-40 Gy in the involved fields (IF), using 6 MV photons, 2 Gy per daily fraction. Total duration of treatment was 28 to 35 days. Results: Using HT, doses to critical organs (heart, lungs, esophagu, and parotids) were significantly decreased and highly conformational irradiation could be delivered to all clinical target volumes. HT delivery was technically possible, even in patients with lesions extremely difficult to irradiate in other conditions or in patients with previous radiation therapy. No Grade 2 or higher toxicity occurred. Four months after the end of HT, 5 patients experienced complete clinical, radiologic, and metabolic response and were subsequently referred for SCT. Conclusions: By more effectively sparing critical organs, HT may contribute to improving the tolerance of debulking irradiation before allograft. Quality of life may be preserved, and doses to the heart may be decreased. This is particularly relevant in heavily treated patients who are at risk for subsequent heart disease. These preliminary results require further prospective assessment.

A case of hyperkalemia after transfusion of irradiated red cell concentrate in mannitol-adenine-phosphate (RC-MAP)

International Nuclear Information System (INIS)

Fukui, Akira; Yokota, Kimio; Aoki, Masanori; Sari, Atsuo

1998-01-01

A 72-year-old male, 45 kg in weight, underwent anterior and posterior fixations of the lumbar vertebra. Preanesthetic blood chemistry was within normal range. Following transfusion of 400 ml of RC-MAP in two hours (11 days after blood collection and 2 days after irradiation at a dose of 20 Gy), and then another 100 ml of 400 ml RC-MAP (12 days after blood collection and 2 days after irradiation at a dose of 20 Gy), the patient's serum kalium value increased from 4.8 to 5.5 mEq/l. Even though the transfusion was immediately discontinued, the level continued to rise to 6.0 mEq/l. It subsequently fell to the normal level with glucose-insulin therapy. The hyperkalemia in this case could have been attributable to the period of storage after irradiation, the transfusion of salvaged autologous blood, and the storage state of RC-MAP. However, since the kalium values of RC-MAP and the salvaged autologous blood were not measured in this case, the exact cause was unknown. In conclusion, hyperkalemia can occur in patients during transfusion of irradiated blood. Therefore, kalium levels should be monitored carefully. (author)

Tumor radiobiology studies with heavy charged-particle beams

International Nuclear Information System (INIS)

Curtis, S.B.; Tenforde, T.S.; Tenforde, S.D.; Parr, S.S.; Flynn, M.J.

1981-01-01

The response of tumor-cell systems to irradiation with carbon, neon, and argon beams at various positions in the plateau and extended peak regions of the Bragg ionization (dose versus depth) curve is being evaluated from experiments conducted both in vivo and in vitro. The radiobiological end points being studied include: tumor volume response, cellular survival after tumor irradiation in situ, cell-kinetic parameters measured by flow cytofluorometry and time-lapse cinematography, and survival of oxic and hypoxic cells irradiated in suspension. One focus of the research effort during the past year has been on the combined effect of radiosensitizing drugs and charged-particle irradiation. In this article, the results are presented of studies on combined drug and radiation treatment of a rat rhabdomyosarcoma tumor and a human melanoma tumor growing in athymic (thymus-less) nude mice

Irradiation strongly reduces tumorigenesis of human induced pluripotent stem cells

International Nuclear Information System (INIS)

Inui, Shoki; Minami, Kazumasa; Ito, Emiko; Imaizumi, Hiromasa; Mori, Seiji; Koizumi, Masahiko; Fukushima, Satsuki; Miyagawa, Shigeru; Sawa, Yoshiki; Matsuura, Nariaki

2017-01-01

Induced pluripotent stem (iPS) cells have demonstrated they can undergo self-renewal, attain pluripotency, and differentiate into various types of functional cells. In clinical transplantation of iPS cells, however, a major problem is the prevention of tumorigenesis. We speculated that tumor formation could be inhibited by means of irradiation. Since the main purpose of this study was to explore the prevention of tumor formation in human iPS (hiPS) cells, we tested the effects of irradiation on tumor-associated factors such as radiosensitivity, pluripotency and cell death in hiPS cells. The irradiated hiPS cells showed much higher radiosensitivity, because the survival fraction of hiPS cells irradiated with 2 Gy was < 10%, and there was no change of pluripotency. Irradiation with 2 and 4 Gy caused substantial cell death, which was mostly the result of apoptosis. Irradiation with 2 Gy was detrimental enough to cause loss of proliferation capability and trigger substantial cell death in vitro. The hiPS cells irradiated with 2 Gy were injected into NOG mice (NOD/Shi-scid, IL-2 Rγnull) for the analysis of tumor formation. The group of mice into which hiPS cells irradiated with 2 Gy was transplanted showed significant suppression of tumor formation in comparison with that of the group into which non-irradiated hiPS cells were transplanted. It can be presumed that this diminished rate of tumor formation was due to loss of proliferation and cell death caused by irradiation. Our findings suggest that tumor formation following cell therapy or organ transplantation induced by hiPS cells may be prevented by irradiation.

Preoperative autologous plateletpheresis in patients undergoing open heart surgery.

Directory of Open Access Journals (Sweden)

Tomar Akhlesh

2003-01-01

Full Text Available Blood conservation is an important aspect of care provided to the patients undergoing cardiac operations with cardiopulmonary bypass (CPB. It is even more important in patients with anticipated prolonged CPB, redo cardiac surgery, patients having negative blood group and in patients undergoing emergency cardiac surgery. In prolonged CPB the blood is subjected to more destruction of important coagulation factors, in redo surgery the separation of adhesions leads to increased bleeding and difficulty in achieving the haemostasis and in patients with negative blood group and emergency operations, the availability of sufficient blood can be a problem. Harvesting the autologous platelet rich plasma (PRP can be a useful method of blood conservation in these patients. The above four categories of patients were prospectively studied, using either autologous whole blood donation or autologous platelet rich plasma (PRP harvest in the immediate pre-bypass period. Forty two patients were included in the study and randomly divided into two equal groups of 21 each, control group (Group I in which one unit of whole blood was withdrawn, and PRP group (Group II where autologous plateletpheresis was utilised. After reversal of heparin, autologous whole blood was transfused in the control group and autologous PRP was transfused in the PRP group. The chest tube drainage and the requirement of homologous blood and blood products were recorded. Average PRP harvest was 643.33 +/- 133.51 mL in PRP group and the mean whole blood donation was 333.75 +/- 79.58 mL in the control group. Demographic, preoperative and intra operative data showed no statistically significant differences between the two groups. The PRP group patients drained 26.44% less (p<0.001 and required 38.5% less homologous blood and blood products (p<0.05, in the postoperative period. Haemoglobin levels on day zero (day of operation and day three were statistically not different between the two groups. We

Development of a Novel Preclinical Pancreatic Cancer Research Model: Bioluminescence Image-Guided Focal Irradiation and Tumor Monitoring of Orthotopic Xenografts1

OpenAIRE

Tuli, Richard; Surmak, Andrew; Reyes, Juvenal; Hacker-Prietz, Amy; Armour, Michael; Leubner, Ashley; Blackford, Amanda; Tryggestad, Erik; Jaffee, Elizabeth M; Wong, John; DeWeese, Theodore L; Herman, Joseph M

2012-01-01

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. B...

Autologous fat transplantation for labia majora reconstruction.

Science.gov (United States)

Vogt, P M; Herold, C; Rennekampff, H O

2011-10-01

A case of autologous fat transplantation for labia majora augmentation after ablative surgery is presented. The patient reported pain and deformity of the left labium majus after resection for Bowen's disease. The symptoms had not been solved by classic plastic surgical reconstructions including a pudendal thigh fasciocutaneous flap. Use of autologous fat transplantation facilitated an improved aesthetic result while preserving residual sensation to the external genitalia and improving symptoms of mucosal exposure and dryness.

Autologous bone marrow purging with LAK cells.

Science.gov (United States)

Giuliodori, L; Moretti, L; Stramigioli, S; Luchetti, F; Annibali, G M; Baldi, A

1993-12-01

In this study we will demonstrate that LAK cells, in vitro, can lyse hematologic neoplastic cells with a minor toxicity of the staminal autologous marrow cells. In fact, after bone marrow and LAK co-culture at a ratio of 1/1 for 8 hours, the inhibition on the GEMM colonies resulted to be 20% less compared to the untreated marrow. These data made LAK an inviting agent for marrow purging in autologous bone marrow transplantation.

Radiotherapy of pineal tumors

International Nuclear Information System (INIS)

Danoff, B.; Sheline, G.E.

1984-01-01

Radiotherapy has universally been used in the treatment of pineal tumors and suprasellar germinomas. Recently however, major technical advances related to the use of the operating microscope and development of microsurgical techniques have prompted a renewed interest in the direct surgical approach for biopsy and/or excision. This interest has resulted in a controversy regarding the role of surgery prior to radiotherapy. Because of the heterogeneity of tumors occurring in the pineal region (i.e., germ cell tumors, pineal parenchymal tumors, glial tumors, and cysts) and their differing biological behavior, controversy also surrounds aspects of radiotherapy such as: the optimal radiation dose, the volume to be irradiated, and indications for prophylactic spinal irradiation. A review of the available data is presented in an attempt to answer these questions

High-dose treatment with autologous stem cell transplantation versus sequential chemotherapy: the GELA experience.

Science.gov (United States)

Bosly, A; Haioun, C; Gisselbrecht, C; Reyes, F; Coiffier, B

2001-07-01

Autologous stem-cell transplantation (ASCT) has permitted to deliver high-dose therapy (HDT). In aggressive lymphomas, the GELA group conducted prospective and retrospective studies comparing HDT + ASCT to conventional sequential chemotherapy. In relapsing patients and in partial remission, retrospective studies showed a survival advantage for HDT + ASCT over sequential chemotherapy. In complete response, advantage for HDT + ASCT was demonstrated in a prospective trial only for patients with high intermediate or high risk in the IPI score. The attainment of a maximal reduction of the tumoral mass before going HDT is very important either in first line or in relapsing patients.

Role of Interleukin-6 in the Radiation Response of Liver Tumors

International Nuclear Information System (INIS)

Chen, Miao-Fen; Hsieh, Ching-Chuan; Chen, Wen-Cheng; Lai, Chia-Hsuan

2012-01-01

Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6–neutralizing antibody for 24 hours or stably transfected with IL-6–silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6–silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma

International Nuclear Information System (INIS)

Franzius, Ch.; Eckardt, J.; Sciuk, J.; Schober, O.; Bielack, S.; Flege, S.; Juergens, H.

2001-01-01

Purpose: Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Patients and Methods: Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. Results: No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors. (orig.)

Experimental study on an active specific immunotherapy modified with irradiation, 1

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Takashima, Hitoshi; Imanaka, Kazufumi

1982-01-01

Active specific immunotherapy using low-dose-irradiated tumor cells and activated mononuclear cells was studied on the transplanted MM 46 tumor of female C3H/He mice aged 12 weeks, after radiotherapy was performed. Local irradiation with the dose of 3,000 rads by high energy electron beam was performed on the fifth day after 5 x 10 6 tumor cells were inoculated in the right hind paws. Tumor cells and mononuclear cells were separated from the tumor tissue which was irradiated with the dose of 2,000 rads on the fifth day and were injected subcutaneously into the left hind paws of the tumor burden mice on the eleventh day. Anti-tumor effect was evaluated by the changes of the tumor volume and survival curves. Tumor growth was significantly inhibited in the group which received irradiation combined with active specific immunotherapy compared with the control group (p < 0.01). Survival rate was significantly higher in the group which received irradiation combined with active specific immunotherapy than the control group (p < 0.025). (author)

The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice

International Nuclear Information System (INIS)

Allam, Ayman; Perez, Luis A.; Huang, Peigen; Taghian, Alphonse; Azinovic, Ignacio; Freeman, Jill; Duffy, Michael; Efird, Jimmy; Suit, Herman D.

1995-01-01

Purpose: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (T pot ) of this tumor to the effective doubling time (T eff ) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. Methods and Materials: The TCP was assessed using the TCD 50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The T pot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to T eff . Results: The TCD 50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD 50 values was significant (p pot (2.4 days) was longer than the calculated T eff in groups 2 and 3 (1.35 days). Conclusion: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment T pot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen

The ultrastructure of tumor cells in patients with rectal cancer after pre-operative irradiation and intra-operative cryotherapy

International Nuclear Information System (INIS)

Vyinnik, Yu.O.; Kotenko, O.Je.; Nevzorov, V.P.; Chyibyisov, L.P.

2000-01-01

Electronic microscopy of the tumor cells was performed to confirm the efficacy of combined pre-operative gamma-therapy and intraoperative cryotherapy (CT). Pre-operative irradiation at the dose of 20 Gy accompanied by intra-operative cryotherapy caused the changes in the ultrastructure, the depth and degree of which allow to consider them destructive and irreversible

Investigation into the incorporation of H3-labelled thymidine into the DNA of a C3H-tumor after irradiation with 35 MeV electrons

International Nuclear Information System (INIS)

Pfersdorff, J.

1978-01-01

The radiation effect on the DNA synthesis of an injected tumor in C 3 H-mice is studied. The tumor is a mammary adenocarcinoma injected into the neck of the animals. A betatron of Brown, Boverie and Cie. of the type Asklepitton 35 is used as radiation source for the generation of fast electrons with an energy of 35 MeV applied to the tumor in the animals through an annular tube of 4 cm in diameter, in the given doses. The tumor-doubling rate during the exponential growth phase is computed to be td = 3.65 days. During irradiation of the tumor, the DNA synthesis is determined by measuring the incorporation of H 3 TdR into the DNA. The results show that the radiation effect on the DNA synthesis is enhanced by every exposure, whereas the additional damage decreases and a recovery can be detected after the first two exposures according to the damage. This study confirms the results of former investigations on tissue cultures. The decisive effect of the radiation is the disturbance of DNA synthesis. Analogous effects can be expected in the irradiation of human tumor cells, though no conclusions can be drawn with regard to fractionation, due to the fast tumor doubling rate of 3.7 days. (orig./MG) [de

Cross-reactivity and phospholipase A2 neutralization of anti-irradiated Bothrops jararaca venom antibodies

International Nuclear Information System (INIS)

Spencer, P.J.; Nascimento, N. do; Paula, R.A. de; Cardi, B.A.; Rogero, J.R.

1995-01-01

The detoxified Bothrops jararaca venom, immunized rabbits with the toxoid obtained and investigated cross-reactivity of the antibodies obtained against autologous and heterelogous venoms was presented. It was also investigated the ability of the IgGs, purified by affinity chromatography, from those sera to neutralize phospholipase. A 2 , an ubiquous enzyme in animal venoms. Results indicate that venom irradiation leads to an attenuation of toxicity of 84%. Cross-reactivity was investigated by ELISA and Western blot and all venoms were reactive to the antibodies. On what refers to phospholipase A 2 activity neutralization, the antibodies neutralized autologous venoms efficiently and, curiously, other venoms from the same genus were not neutralized, while Lachesis muta venom, a remote related specier, was neutralized by this serum. These data suggest that irradiation preserve important epitopes for induction of neutralizing antibodies and that these epitopes are not shared by all venoms assayed. (author). 8 refs, 2 figs, 3 tabs

Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

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Alexander RW

2013-04-01

Full Text Available Robert W Alexander,1 David Harrell2 1Department of Surgery, School of Medicine and Dentistry, University of Washington, Seattle, WA, USA; 2Harvest-Terumo Inc, Plymouth, MA, USA Objectives: Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG with use of disposable, microcannula systems. Design: Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results: Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion: Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are

High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

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Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Willis, Callen [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Banerjee, Debarshi [Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Mitchell, Jason [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Hernandez, Sonia L. [Department of Surgery, University of Chicago, Chicago, Illinois (United States); Hei, Tom [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Kadenhe-Chiweshe, Angela [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Yamashiro, Darrell J. [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York (United States); Connolly, Eileen P., E-mail: epc2116@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States)

2016-04-01

Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 9

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji

1983-01-01

We have already reported the remarkable effect of an active specific immunotherapy using cryopreserved tumor cells and infiltrating mononuclear cells prepared from a low-dose irradiated tumor tissue after cytoreductive radiotherapy. In the present study, the effect of a biological response modifier, OK-432 combined with the active specific immunotherapy was investigated. Twelve-week-aged female C3H/He mice transplanted with MM 46 tumor cells were received local radiotherapy with a dose of 3,000 rads by high energy electron beams on the fifth day after inoculation. The tumor cells and infiltrating mononuclear cells cryopreserved for two months were thawed and treated with mitomycin-C at concentration of 20 μg/10 7 cells at 37 0 C for 30 min. Then, these cells were injected subcutaneously into the left hind paws as a mitomycin C-treated, cryopreserved active specific immunotherapy on the thirteenth day, and daily dose of 1 KE of OK-432 was injected intraperitoneally from the sixth to the tenth days. The inhibition of the tumor growth was similarly observed in the group which received this active specific immunotherapy combined with a biological response modifier, OK-432. (author)

Metastasis and growth of friend tumor cells in irradiated syngeneic hosts

International Nuclear Information System (INIS)

Matioli, G.

1974-01-01

Friend tumor cells (FTC) have been studied by growing them in lethally irradiated syngeneic mice. After establishing the FTC dilution factor (delta), extinction factor (Q), and the optimal time for colony counts, the FTC kinetic was analyzed by the recovery curve method. It was found that FTC growth is different from that experienced by normal or leukemic Friend stem cells when tested by the same in vivo assay. The most interesting differences were the high metastatic activity, the lack of differentiation, the deterministic growth, and the independence from the spleen microenvironment experienced by the FTC, in contrast with the normal and leukemic stem cells. In addition, the estimate of the critical size the FTC colony has to reach before releasing the first metastatic cells is presented. (U.S.)

Effects of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in tumor-bearing mice

International Nuclear Information System (INIS)

Yu Hongsheng; Lu Yanda

2001-01-01

Objective: To study the effect of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in the tumor-bearing mice. Methods: Kunming strain male mice were implanted with S 180 sarcoma cells in the right inguen subcutaneously as an experimental in situ animal model. Six hours before implantation the mice were given 75 mG whole-body X-ray irradiation and tumor-formation rate was counted 5 days late. From then, every two days the tumor volume was measured to draw a tumor growth curve. Fifteen days later, all mice were killed to measure the tumor weight, observe the necrosis area and the tumor-infiltration lymphoreticular cells (TIL) in the tumor pathologically. At the same time, erythrocyte immune function and activity of SOD were tested. Results: (1) The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without a pre-exposed (P < 0.05). (2) The tumor growth slowed down significantly in mice receiving a low does irradiation; The average tumor weight in mice receiving a low dose irradiation was lighter too (P < 0.05). (3) The tumor necrosis areas were larger and TILs were more in the irradiation group than those of the control group. (4) The erythrocyte immune function and activity of SOD in the irradiation group were all higher significantly than those of the control group ( P < 0.05). Conclusion: Low dose radiation could markedly increase anti-tumor ability of the organism and improve the erythrocyte immune function and activity of SOD in red cells, suggesting it could be useful in clinical cancer treatment

Preoperative autologous plateletpheresis in patients undergoing open heart surgery.

Science.gov (United States)

Tomar, Akhlesh S; Tempe, Deepak K; Banerjee, Amit; Hegde, Radhesh; Cooper, Andrea; Khanna, S K

2003-07-01

Blood conservation is an important aspect of care provided to the patients undergoing cardiac operations with cardiopulmonary bypass (CPB). It is even more important in patients with anticipated prolonged CPB, redo cardiac surgery, patients having negative blood group and in patients undergoing emergency cardiac surgery. In prolonged CPB the blood is subjected to more destruction of important coagulation factors, in redo surgery the separation of adhesions leads to increased bleeding and difficulty in achieving the haemostasis and in patients with negative blood group and emergency operations, the availability of sufficient blood can be a problem. Harvesting the autologous platelet rich plasma (PRP) can be a useful method of blood conservation in these patients. The above four categories of patients were prospectively studied, using either autologous whole blood donation or autologous platelet rich plasma (PRP) harvest in the immediate pre-bypass period. Forty two patients were included in the study and randomly divided into two equal groups of 21 each, control group (Group I) in which one unit of whole blood was withdrawn, and PRP group (Group II) where autologous plateletpheresis was utilised. After reversal of heparin, autologous whole blood was transfused in the control group and autologous PRP was transfused in the PRP group. The chest tube drainage and the requirement of homologous blood and blood products were recorded. Average PRP harvest was 643.33 +/- 133.51 mL in PRP group and the mean whole blood donation was 333.75 +/- 79.58 mL in the control group. Demographic, preoperative and intra operative data showed no statistically significant differences between the two groups. The PRP group patients drained 26.44% less (pblood products (pconservation in terms of better haemostasis, and less requirement of blood and blood products in the postoperative period as compared with the autologous whole blood donation. This technique can be especially useful in the

Biological Reconstruction Following the Resection of Malignant Bone Tumors of the Pelvis

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Frank Traub

2013-01-01

Full Text Available Background. Surgical treatment of malignant pelvic bone tumors can be very challenging. The objective of this retrospective study was to evaluate the oncological as well as the clinical and functional outcome after limb salvage surgery and biological reconstruction. Methods. The files of 27 patients with malignant pelvic bone tumors, who underwent surgical resection at our department between 2000 and 2011, were retrospectively analyzed (9 Ewing's sarcoma, 8 chondrosarcoma, 4 osteosarcoma, 1 synovial sarcoma, 1 malignant fibrous histiocytoma, and 4 carcinoma metastases. Results. After internal hemipelvectomy reconstruction was performed by hip transposition (, using autologous nonvascularised fibular graft ( or autologous iliac crest bone graft (. In one patient a proximal femor prothetis and in three patients a total hip prosthesis was implanted at the time of resection. The median follow-up was 33 months. Two- and five-year disease-specific survival rates of all patients were 86.1% and 57.7%, respectively. The mean functional MSTS score was 16.5 (~55% for all patients. Conclusion. On the basis of the oncological as well as the clinical and functional outcome, biological reconstruction after internal hemipelvectomy seems to be a reliable technique for treating patients with a malignant pelvic bone tumor.

Lysis of autologous human macrophages by lymphokine-activated killer cells: interaction of effector cell and target cell conjugates analyzed by scanning electron microscopy.

Science.gov (United States)

Streck, R J; Helinski, E H; Ovak, G M; Pauly, J L

1990-09-01

Lymphokine (i.e., interleukin 2; IL-2)-activated killer (LAK) cells derived from normal human blood are known to destroy human tumor target cells. Accordingly, immunotherapy modalities using IL-2, either alone or in combination with LAK cells, have been evaluated for eradicating metastatic cancer. In studies conducted to characterize receptors on LAK cell membrane ultrastructures, we observed that LAK cells kill autologous human monocyte-derived macrophages (M phi). In these experiments, peripheral blood mononuclear cells of a healthy adult donor were cultured to generate LAK cells and autologous non-adherent M phi. Thereafter, conjugates were prepared by incubating for 3 h autologous populations of LAK cells and M phi. Examination of the conjugates by scanning electron microscopy (SEM) identified LAK cell-mediated killing of M phi. Moreover, SEM analysis of the LAK cell membrane architecture identified microvilli-like ultrastructures that provided a physical bridge that joined together the LAK cell and M phi. The immunological mechanism(s) underling LAK cell killing of autologous M phi is not known; nevertheless, these conjugates will provide a useful model to study membrane receptors on ultrastructures that mediate the initial stages of cytolysis that include target cell recognition and cell-to-cell adhesion. The results of our observations and the findings of other investigators who have also demonstrated LAK cell killing of autologous normal human leukocytes are discussed in the context of the association of IL-2 and IL-2-activated killer cells with side effects observed in ongoing clinical trials and with autoimmune disorders.

Studies of skin cancer and thyroid tumors after irradiation of the head and neck

International Nuclear Information System (INIS)

Shore, R.E.; Moseson, M.; Hildreth, N.

1992-01-01

Two longitudinal studies of children given medical X-irradiation to the head and neck are described, one of 2,650 infants who received x-ray treatment for enlarged thymus glands and the other of 2,200 children who received x-ray treatment for tinea capitis (ringworm of the scalp). The thymus study showed a dose-related excess of thyroid cancer and a long period of excess risk. The tinea study also showed an excess of thyroid tumors even though the thyroid dose was only about 0.06 Gy. An excess of non-melanotic skin cancers has also occurred in the tinea study, but no evidence for excess malignant melanomas. The skin cancer excess is not evident among blacks in the study, and, among Caucasians, it is more prominent among those with a light complexion. This suggests that host-susceptibility to ultraviolet effects is an important modifier of skin cancer risk from ionizing irradiation. (author)

Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

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Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Yoo, Young-Choon [Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Hwang, Young-Jeong [Division of Food Science, International University of Korea, Jinju 660-759 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

2009-07-15

Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-{alpha} and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX (P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

International Nuclear Information System (INIS)

Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il; Yoo, Young-Choon; Byun, Myung-Woo; Hwang, Young-Jeong; Lee, Ju-Woon

2009-01-01

Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-α and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX (P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

Transplantation of autologous bone marrow in three patients with acute myelogenous leukaemia during the first remission

International Nuclear Information System (INIS)

Loewenberg, B.; Sizoo, W.; Sintnicolaas, K.; Hendriks, W.D.H.; Poel, J. van der; Abels, J.; Dzoljic, G.; Bekkum, D.W. van; Wagemaker, G.

1983-01-01

A report is presented on the first results of transplantation of autologous bone marrow in 3 adult patients with acute myelogenous leukaemia. The treatment consisted of intensive chemotherapy and whole-body irradiation and was followed by transplantation of a limited number of non-purified bone-marrow cells that had previously been collected from the patient. In all three patients, transplantation was followed by a stable remission. One patient had a fatal recurrence after a total period of 21 months of remission. In 2 patients, the remissions continue. The clinical significance of these findings is discussed. (Auth.)

Case report: long-term survival of an infant syndromic patient affected by atypical teratoid-rhabdoid tumor

International Nuclear Information System (INIS)

Modena, Piergiorgio; Maestro, Roberta; Giangaspero, Felice; Massimino, Maura; Sardi, Iacopo; Brenca, Monica; Giunti, Laura; Buccoliero, Anna Maria; Pollo, Bianca; Biassoni, Veronica; Genitori, Lorenzo; Antonelli, Manila

2013-01-01

Atypical teratoid rhabdoid tumor (ATRT) patients display a dismal median overall survival of less than 1 year. A consistent fraction of cases carries de-novo SMARCB1/INI1 constitutional mutations in the setting of the “rhabdoid tumor predisposition syndrome” and the outcome is worst in infant syndromic ATRT patients. We here describe a patient affected by mosaic Klinefelter syndrome and by rhabdoid tumor predisposition syndrome caused by constitutional SMARCB1/INI1 heterozygous mutation c.118C>T (Arg40X). Patient’s ATRT primary tumor occurred at 2 years of age concurrent with metastatic lesions. The patient was rendered without evidence of disease by combined surgery, high-dose poli-chemotherapy and craniospinal irradiation, followed by autologous hematopoietic stem cell transplantation. At the onset of a spinal lesion 5.5 years later, both tumors were pathologically and molecularly evaluated at the national central pathology review board and defined as ATRT in a syndromic patient, with strong evidence of a clonal origin of the two lesions. The patient was then treated according to SIOP guidelines and is now alive without evidence of disease 24 months after the detection of metastatic disease and 90 months after the original diagnosis. The report underscores the current utility of multiple comprehensive approaches for the correct diagnosis and clinical management of patients affected by rare and atypical brain neoplasms. Successful local control of disease and achievement of long-term survival is possible in ATRT patients even in the setting of rhabdoid tumor predisposition syndrome, infant age at diagnosis and metastatic spread of disease, thus justifying the efforts for the management of this severe condition

Cost effectiveness of autologous blood transfusion – A developing ...

African Journals Online (AJOL)

An autologous blood donation program was set up at National Orthopaedic Hospital, Igbobi Lagos in 1992 in response to the rising sero prevalence of HIV observed in our “relative replacement” donors. A retrospective batch analysis of patients who received autologous transfusion and those who received homologous ...

Studies on anti-tumor effect of electromagnetic waves

International Nuclear Information System (INIS)

Kadota, Ikuhito; Wakabayashi, Toshio; Ogoshi, Kyoji; Kamijo, Akemi

1995-01-01

Hyperthermia have treated cancer with thermal effect of electromagnetic waves for biological systems, but the expected effect is not shown. Also non-thermal effect of electromagnetic waves is out of consideration. If irradiation conditions of electromagnetic waves with non-thermal anti-tumor effect are obtained, we can expect newly spread in cancer therapy. We had in vivo experiments that electromagnetic waves were irradiated to mice. In some irradiation conditions, the non-thermal anti-tumor effect of electromagnetic waves showed. In order to specify the irradiation conditions, we had in vitro experiments. We found that activity ratio of tumor cells which was measured by MTT method depended on irradiation time and power of electromagnetic waves. These results are useful for the cancer therapy. (author)

Mechanism of suppression of normal hemopoietic activity by lymphokine-activated killer cells and their products

International Nuclear Information System (INIS)

Gibson, F.M.; Malkovska, V.; Myint, A.A.; Meager, A.; Gordon-Smith, E.C.

1991-01-01

Interleukin 2 (IL-2)-activated lymphocytes (lymphokine-activated killer [LAK] cells) have been shown to inhibit the formation of autologous human granulocyte-macrophage hemopoietic progenitors (granulocyte-macrophage colony-forming units, CFU-GM) in vitro. Effects of LAK cells on these progenitors may include a number of different mechanisms. LAK cells are potent cytotoxic lymphocytes capable of lysing certain normal autologous cells. They also produce cytokines known to inhibit hemopoiesis (interferon gamma [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]) or enhance it (granulocyte-macrophage colony-stimulating factor, GM-CSF). In the authors' current study they analyzed the mechanism of suppression of autologous CFU-GM by LAK cells. Their results suggest that LAK cells are not directly cytotoxic to normal CFU-GM. They show that it is possible to abolish the hemopoiesis-inhibiting activity of LAK cells without abrogating their cytotoxicity against tumor cell lines using inhibitors of DNA synthesis, namely hydroxyurea or irradiation

Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels

International Nuclear Information System (INIS)

Loevey, J.; Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J.; Dobos, J.; Vago, A.; Kasler, M.; Doeme, B.; Tovari, J.

2008-01-01

Background and purpose: tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPOα on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. Material and methods: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPOα at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPOα on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1α expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPOα and irradiation were also tested in vitro. Results: in vitro, rHuEPOα treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPOα administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1α expression but had no effect on tumor growth. At the same time rHuEPOα treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 ± 4.7 mg and 34.9 ± 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. Conclusion: rHuEPOα treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1α expression, but also by destroying tumoral vessels. (orig.)

Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors.

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Young Bae Choi

Full Text Available We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs. During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant, bacteremia, urinary tract infection (UTI, respiratory virus infection, and varicella zoster virus (VZV reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant, bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection. Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.

Autologous patch graft in tube shunt surgery.

Science.gov (United States)

Aslanides, I M; Spaeth, G L; Schmidt, C M; Lanzl, I M; Gandham, S B

1999-10-01

To evaluate an alternate method of covering the subconjunctival portion of the tube in aqueous shunt surgery. Evidence of tube erosion, graft-related infection, graft melting, or other associated intraocular complications were evaluated. A retrospective study of 16 patients (17 eyes) who underwent tube shunt surgery at Wills Eye Hospital between July 1991 and October 1996 was conducted. An autologous either "free" or "rotating" scleral lamellar graft was created to cover the subconjunctival portion of the tube shunt. All patients were evaluated for at least 6 months, with a mean follow-up of 14.8 months (range 6-62 months). All eyes tolerated the autologous graft well, with no clinical evidence of tube erosion, or graft-related or intraocular complications. Autologous patch graft in tube shunt surgery appears--in selected cases--to be an effective, safe and inexpensive surgical alternative to allogenic graft materials. It also offers ease of availability, and eliminates the risk of transmitting infectious disease.

Experimental study on active specific immunotherapy utilizing the immune reaction of low-dose irradiated tumor tissue, 4

International Nuclear Information System (INIS)

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

1982-01-01

We have already reported that the effectiveness of active specific immunotherapy using low-dose irradiated tumor cells and infiltrating mononuclear cells. The present study was designed to investigate the effect of non-specific immunopotentiator combined with the active specific immunotherapy. Twelve-week-aged female C3H/He mice transplanted with MM46 tumor were received local radiotherapy with the dose of 3,000 rads by high energy electron beam on the sixth day after inoculation. Active specific immunotherapy was performed on the 13th day, and daily dose of 1.0 KE of OK-432 was injected intraperitoneally from the 13th day to the 17th day. The inhibition of the tumor growth and the elongation of survival period were noted in the group which received active specific immunotherapy combined with non-specific immunopotentiator, OK-432 compared with that active specific immunotherapy alone. (author)

Study on the induction of thyroid tumors in rats using x irradiation in conjunction with a goitrogen. [1 methyl--2 mercaptoimidazole (methimazole)

Energy Technology Data Exchange (ETDEWEB)

Mahler, P.

1979-01-01

The influence of acute localized thyroid x irradiation and chronic goitrogen administration, separately or combined, on thyroid tumor formation in mature female rats was studied. In the first experiment, the radiation doses were 0, 80, 160, 320, or 640 rads, and the dosages of goitrogen were 0, 4, or 40 parts per million (ppM) of 1 methyl - 2 mercaptoimidazole (MMI). The incidence of rats with thyroid tumors in any treated group receiving 0 or 4 ppM MMI was not significantly greater than the incidence in the nontreated control group. However, the incidence in any of the 40 ppM MMI groups was significantly greater than that in the nontreated control group. At all the radiation doses other than 80 rads, the incidence was significantly greater than that in the non-irradiated group. No significant difference was seen in the incidence of rats with thyroid tumors on the basis of radiation dose. The incidence was so high at 80 rads that there was little margin for further increase by increasing the radiation dose. The mean serum thyroxine levels at 40 ppM MMI, 4 ppM MMI, and 0 ppM MMI were 1.9, 3.5, and 3.7 ..mu..g/100 ml, respectively. No markedeffect of thyroid irradiation on mean serum thyroxine levels was seen. In the second experiment, rats receiving 200 ppM MMI and thyroid irradiation were sacrificed at 7-1/2 months after treatment. Nearly all rats in the 0 and 80 rad groups and all in the 160, the 320, and the 640 rad groups had thyroid tumors. In the third experiment, serum T/sub 4/ levels were measured in treated rats. Rats receiving 640 rads + 0 ppM MMI showed a slight decrease in serum T/sub 4/, while no change in serum T/sub 4/ levels was seen in rats receiving 0 rads + 4 ppM MMI or 640 rads + 4 ppM MMI. All rats receiving 40 ppM MMI, regardless of radiation dose, showed decreased serum T/sub 4/ levels.

Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (2). Combination effect on MM102 syngeneic tumor

Energy Technology Data Exchange (ETDEWEB)

Shiio, Tsuyoshi; Ohishi, Kazuo; Tsuchiya, Yoshiharu; Niitsu, Iwayasu; Hayashibara, Hiromi; Yoshihama, Takashi; Moriyuki, Hirobumi

1988-03-01

C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation.

Four-dimensional treatment planning and fluoroscopic real-time tumor tracking radiotherapy for moving tumor

International Nuclear Information System (INIS)

Shirato, Hiroki; Shimizu, Shinichi; Kitamura, Kei; Nishioka, Takeshi; Kagei, Kenji; Hashimoto, Seiko; Aoyama, Hidefumi; Kunieda, Tatsuya; Shinohara, Nobuo; Dosaka-Akita, Hirotoshi; Miyasaka, Kazuo

2000-01-01

Purpose: To achieve precise three-dimensional (3D) conformal radiotherapy for mobile tumors, a new radiotherapy system and its treatment planning system were developed and used for clinical practice. Methods and Materials: We developed a linear accelerator synchronized with a fluoroscopic real-time tumor tracking system by which 3D coordinates of a 2.0-mm gold marker in the tumor can be determined every 0.03 second. The 3D relationships between the marker and the tumor at different respiratory phases are evaluated using CT image at each respiratory phase, whereby the optimum phase can be selected to synchronize with irradiation (4D treatment planning). The linac is triggered to irradiate the tumor only when the marker is located within the region of the planned coordinates relative to the isocenter. Results: The coordinates of the marker were detected with an accuracy of ± 1 mm during radiotherapy in the phantom experiment. The time delay between recognition of the marker position and the start or stop of megavoltage X-ray irradiation was 0.03 second. Fourteen patients with various tumors were treated by conformal radiotherapy with a 'tight' planning target volume (PTV) margin. They were surviving without relapse or complications with a median follow-up of 6 months. Conclusion: Fluoroscopic real-time tumor tracking radiotherapy following 4D treatment planning was developed and shown to be feasible to improve the accuracy of the radiotherapy for mobile tumors

Cyclophosphamide-induced cardiomyopathy in a patient with seminoma and a history of mediastinal irradiation

International Nuclear Information System (INIS)

Kamezaki, Kenjirou; Fukuda, Takahiro; Makino, Shigeyoshi; Harada, Mine

2005-01-01

A 17-year-old man with mediastinal seminoma was treated with chemotherapy and mediastinal irradiation therapy. Then he received high-dose chemotherapy containing cyclophosphamide (CY) followed by autologous peripheral blood stem cell transplantation. He suffered from CY-induced cardiomyopathy beginning six days after the administration of high-dose CY. The predictable factors associated with the onset of CY-induced cardiomyopathy are not precisely known. It is suggested that the history of mediastinal irradiation was responsible for the onset of cardiomyopathy. (author)

Myelopoiesis in whole-body-irradiated beagles

International Nuclear Information System (INIS)

Stevenson, A.F.G.

1985-01-01

The influence of dose-rate (DR) (either 5.2 or 52 cGy/min.) on the regeneration of bone marrow (BM) myelopoietic progenitor cells was studied in beagles after exposure to whole-body-irradiation (235, 375 and 1500 cGy + autologous BM-transplantation). Myelopoietic progenitor cells were assayed as colony-forming units in agar cultures (GM-CFU), in correlation with the colony-stimulation activity (CSA) in serum. At 235 cGy, the influence of DR on the recovery of GM-CFU was insignificant. However, at 375 cGy, the recovery was critically dependent on the DR. Depletion of GM-CFU numbers elevated CSA levels above pre-irradiation values. The DR determines the regenerative ability when the dose itself is critical to survival of the least number of hematopoietic stem cells (HSC) necessary for restitution. (author)

Investigation of change of tumor optical properties after laser-induced plasmon-resonant photothermal treatment of transplanted tumors in rats

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Genin, Vadim D.; Genina, Elina A.; Bucharskaya, Alla B.; Tuchin, Valery V.; Khlebtsov, Nikolay G.; Terentyuk, Georgy S.; Bashkatov, Alexey N.

2018-04-01

The paper presents the investigation of change of tumor optical properties of the rat tumor doped by gold nanoparticles after laser-induced plasmon-resonant photothermal treatment. To obtain the model tumors the rats have been implanted by suspension of alveolar kidney cancer cells. An hour before the experiment the animals have been injected by the suspension of gold nanorods intratumorally. For irradiation a diode laser with wavelength 808 nm has been used. After the irradiation the tumor has been removed and sliced. Spectra of total and collimated transmission and diffuse reflectance of the samples of different layers of the tumors have been measured in the wavelength range 350-2500 nm. Absorption, scattering, reduced scattering coefficients and scattering anisotropy factor of tumor tissues have been calculated with inverse adding-doubling method. The results of the experiment have shown that after doping the tumor tissue by the plasmon resonant nanoparticles and NIR laser irradiating, there is the decreases of absorption as well as scattering properties of the tumor and surrounding tissues. However, despite the sufficiently high temperature on the surface (about 80°C), the changes in the center of the tumor are insignificant.

Validated Outcomes in the Grafting of Autologous Fat to the Breast: The VOGUE Study. Development of a Core Outcome Set for Research and Audit.

Science.gov (United States)

Agha, Riaz A; Pidgeon, Thomas E; Borrelli, Mimi R; Dowlut, Naeem; Orkar, Ter-Er K; Ahmed, Maziyah; Pujji, Ojas; Orgill, Dennis P

2018-05-01

Autologous fat grafting is an important part of the reconstructive surgeon's toolbox when treating women affected by breast cancer and subsequent tumor extirpation. The debate over safety and efficacy of autologous fat grafting continues within the literature. However, work performed by the authors' group has shown significant heterogeneity in outcome reporting. Core outcome sets have been shown to reduce heterogeneity in outcome reporting. The authors' goal was to develop a core outcome set for autologous fat grafting in breast reconstruction. The authors published their protocol a priori. A Delphi consensus exercise among key stakeholders was conducted using a list of outcomes generated from their previous work. These outcomes were divided into six domains: oncologic, clinical, aesthetic and functional, patient-reported, process, and radiologic. In the first round, 55 of 78 participants (71 percent) completed the Delphi consensus exercise. Consensus was reached on nine of the 13 outcomes. The clarity of the results and lack of additional suggested outcomes deemed further rounds to be unnecessary. The VOGUE Study has led to the development of a much-needed core outcome set in the active research front and clinical area of autologous fat grafting. The authors hope that clinicians will use this core outcome set to audit their practice, and that researchers will implement these outcomes in their study design and reporting of autologous fat grafting outcomes. The authors encourage journals and surgical societies to endorse and encourage use of this core outcome set to help refine the scientific quality of the debate, the discourse, and the literature. Therapeutic, V.

Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. V. Bleomycin

International Nuclear Information System (INIS)

Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

1979-01-01

Experiments have been carried out to determine the effect of different time intervals between the administration of x-radiation (1200 rad) and bleomycin (20 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered by the intraperitoneal route either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For a single administration at this dose level, bleomycin alone did not produce a significant growth delay in any of the tumors. In the RIF-1 tumor, growth delays following combination treatments were equal to the addition of the single agent growth delays. In two experiments with EMT6, contrary results were obtained, one producing longer delays following combination treatments than predicted and the other producing shorter delays. This is apparently due to the variability in the growth delay after treatment with radiation alone for this tumor. For the KHT tumor, only small differences from the addition of single agent delays were seen

Cord Blood Banking Standards: Autologous Versus Altruistic.

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Armitage, Sue

2015-01-01

Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards.

In vivo tumor radiobiology of heavy charged particles

International Nuclear Information System (INIS)

Curtis, S.B.; Tenforde, T.S.

1980-01-01

The response of tumor cells systems to irradiation with carbon, neon and argon beams at various positions in the plateau and extended-peak regions of the Bragg ionization curve is being evaluated from experiments conducted both in vivo and in vitro. The radiobiological end points being studied include: tumor volume response, cellular survival after tumor irradiation in situ, and cell-kinetic parameters

Equivalence of hyperfractionated and continuous brachytherapy in a rat tumor model and remarkable effectiveness when preceded by external irradiation

International Nuclear Information System (INIS)

Veninga, Theo; Visser, Andries G.; Berg, Ad P. van den; Hooije, Christel van; Geel, Cornelis A.J.F. van; Levendag, Peter C.

2001-01-01

Purpose: In clinical brachytherapy, there is a tendency to replace continuous low-dose-rate (LDR) irradiation by either single-dose or fractionated high-dose-rate (HDR) irradiation. In this study, the equivalence of LDR treatments and fractionated HDR (2 fractions/day) or pulsed-dose-rate (PDR, 4 fractions/day) schedules in terms of tumor cure was investigated in an experimental tumor model. Methods and Materials: Tumors (rat rhabdomyosarcoma R1M) were grown s.c. in the flank of rats and implanted with 4 catheters guided by a template. All interstitial radiation treatment (IRT) schedules were given in the same geometry. HDR was given using an 192 Ir single-stepping source. To investigate small fraction sizes, part of the fractionated HDR and PDR schedules were applied after an external irradiation (ERT) top-up dose. The endpoint was the probability of tumor control at 150 days after treatment. Cell survival was estimated by excision assay. Results: Although there was no fractionation effect for fractionated HDR given in 1 or 2 fractions per day, TCD 50 -values were substantially lower than that for LDR. A PDR schedule with an interfraction interval of 3 h (4 fractions/day), however, was equivalent to LDR. The combination of ERT and IRT resulted in a remarkably increased tumor control probability in all top-up regimens, but no difference was found between 2 or 4 fractions/day. Catheter implantation alone decreased the TCD 50 for single-dose ERT already by 17.4 Gy. Cell viability assessed at 24 h after treatment demonstrated an increased effectiveness of interstitial treatment, but, after 10 Gy ERT followed by 10 Gy IRT (24-h interval), it was not less than that calculated for the combined effect of these treatments given separately. Conclusion: In full fractionation schedules employing large fractions and long intervals, the sparing effect of sublethal damage repair may be significantly counteracted by reoxygenation. During 3-h intervals, however, repair may be

Production of a Dendritic Cell-Based Vaccine Containing Inactivated Autologous Virus for Therapy of Patients with Chronic Human Immunodeficiency Virus Type 1 Infection▿

Science.gov (United States)

Whiteside, Theresa L.; Piazza, Paolo; Reiter, Amanda; Stanson, Joanna; Connolly, Nancy C.; Rinaldo, Charles R.; Riddler, Sharon A.

2009-01-01

In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8+ and CD4+ T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4+ T cells with the virus; (iii) inactivation of the virus in CD4+ T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4+ T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4+ T cells. CD4+ T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID50; which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4+ T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID50 of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 μg/ml) and UVB irradiation (312 nm) reduced the TCID50 of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4+ T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137). PMID:19038780

Production of a dendritic cell-based vaccine containing inactivated autologous virus for therapy of patients with chronic human immunodeficiency virus type 1 infection.

Science.gov (United States)

Whiteside, Theresa L; Piazza, Paolo; Reiter, Amanda; Stanson, Joanna; Connolly, Nancy C; Rinaldo, Charles R; Riddler, Sharon A

2009-02-01

In preparation for a pilot clinical trial in patients with chronic human immunodeficiency virus type 1 (HIV-1) infection, a novel dendritic cell (DC)-based vaccine is being manufactured. The trial will test the hypothesis that isolated endogenous virus presented by DCs serves as a potent immunogen for activation of CD8(+) and CD4(+) T cells specific for a broad range of autologous HIV-1 antigens. Production of the vaccine under good manufacture practice conditions involves (i) autologous virus isolation; (ii) superinfection of CD4(+) T cells with the virus; (iii) inactivation of the virus in CD4(+) T cells, T-cell apoptosis, and coincubation of T cells with autologous DCs; and (iv) product testing and release. Endogenous virus was isolated from peripheral blood-derived CD4(+) T cells of three HIV-1-positive subjects by coincubation with autologous OKT-3-stimulated CD4(+) T cells. CD4(+) T-cell supernatants were tested for p24 levels by enzyme-linked immunosorbent assay (>25 ng/ml) and for the 50% tissue culture infective doses (TCID(50); which ranged from 4,642 to 46,416/ml on day 19 of culture). Autologous CD4(+) T cells that were separated on immunobeads (>95% purity) and superinfected with virus-expressed p24 (28 to 54%) had TCID(50) of >400/ml on days 5 to 10. Virus inactivation with psoralen (20 microg/ml) and UVB irradiation (312 nm) reduced the TCID(50) of the supernatants from 199,986 to 11/ml (>99%). 7-Amino-actinomycin D-positive, annexin V-positive CD4(+) T cells were fed to autologous DCs generated by using the Elutra cell separation system and the Aastrom system. Flow analysis showed that DC loading was complete in 24 h. On the basis of these translational results and experience with the generation of DCs from HIV-1-infected patients in a previous clinical trial, the Investigational New Drug application for clinical vaccination was submitted and approved by the FDA (application no. BB-IND-13137).

Preoperative irradiation of hypernephroid carcinoma

International Nuclear Information System (INIS)

Akbar, D.

1982-01-01

Since 1969, preoperative irradiation of hypernephiroid carcinoma has been a routine measure at the Steglitz medical clinic: It consists in the application of a focal dose of 30 Gy, fractionated into doses of 2.5 Gy, as Betatron pendulum irradiation (42 MeV photons) covering the para-aortic lymph nodes. After a treatment-free interval of 3 weeks, radical nephrectomy is carried through. Of 178 patients, 47 were in tumor stage I, 15 in stage II, 83 in stage III and 33 in stage IV. In 99 patients the treatment dated back longer than 5 years; the survival rate was 52%. 67% of the patients had survived longer than 3 years. Operation lethality was 3%. The preoperative irradiation pursues the following aims: 1. Devitalization of potentially proliferating cells in the tumor periphery, and thus prevention of displaced tumor cells growing on and postoperative local recidivations; 2. Shrinking of the tumor, facilitating the surgical intervention. In a third of the cases a measurable alteration of the tumor was confirmed by X-ray. The low operation lethality of 3% is attributed to this. (orig./MG) [de

Irradiation of metastatic carcinoma parotid

International Nuclear Information System (INIS)

Jack, G.A.

1981-01-01

Acinic cell carcinomas of the parotid should be considered distinct malignancies despite descriptions of low-grade malignant potential and innocuous histologic patterns. Benign-appearing tumors frequently have a clinically malignant course. Blood-borne metastases may oocur early despite gross and microscopic innocence. Indolent growth may be a characteristic of local disease, which may then be approached with less than radical parotidectomy and sacrifice of the facial nerve. These tumors prove to be radiosensitive. More agressive postoperative irradiation and palliative irradiation is recommended. Two cases of successful palliation of spinal metastases are presented as examples of radiosensitivity of this tumor

Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

International Nuclear Information System (INIS)

Garbe, Yvette; Klier, Ulrike; Linnebacher, Michael

2011-01-01

Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells. Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells. We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays. The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4 + , activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested) could be observed. Cellular fusions of MSI + carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These hybrid cells may have great potential for cellular immunotherapy and

HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

Directory of Open Access Journals (Sweden)

Andrea Pession

2011-06-01

Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

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)

Time course of development of metastasis in irradiated Lewis lung carcinoma

International Nuclear Information System (INIS)

Ohizumi, Yukio; Maezawa, Hiroshi; Mori, Tomoyuki

1988-01-01

The influence of local irradiation on the development of metastases and primary tumor volume was studied in Lewis lung carcinoma growing intramuscularly in the hind leg of C57BL/6 mice. The time course of development of metastases was determined from the size of the lung colonies at autopsy by determining the growth rate of the colonies. Irradiation within five days after tumor cell injection inhibited the incidence of metastases in accordance with irradiation dose. For irradiation more than seven days after the injection, promotion of metastases was observed around the time of the experiment as a function of irradiation dose and tumor volume. After the irradiation phase, the development of metastases was inhibited in accordance with radiation dose. When delay in metastasis was defined as additional days needed to develop two or ten colonies compared with controls, the relationship between delay and dose was linear. At the regrowth phase of the primary tumor, the incidence of metastases from the irradiated tumor was reduced in comparison with that from unirradiated tumors of the same size. Inhibition of metastases was observed only at 5 Gy and showed slight dose-dependency. Mechanisms in the development of metastases as they related to these findings are also discussed. (autho)

Radiation induction of drug resistance in RIF-1 tumors and tumor cells

International Nuclear Information System (INIS)

Hopwood, L.E.; Moulder, J.E.

1989-01-01

The RIF-1 tumor cell line contains a small number of cells (1-20 per 10(6) cells) that are resistant to various single antineoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), and adriamycin (ADR). For 5FU the frequency of drug resistance is lower for tumor-derived cells than for cells from cell culture; for MTX the reverse is true, and for ADR there is no difference. In vitro irradiation at 5 Gy significantly increased the frequency of drug-resistant cells for 5FU, MTX, and ADR. In vivo irradiation at 3 Gy significantly increased the frequency of drug-resistant cells for 5FU and MTX, but not for ADR. The absolute risk for in vitro induction of MTX, 5FU, and ADR resistance, and for in vivo induction of 5FU resistance, was 1-3 per 10(6) cells per Gy; but the absolute risk for in vivo induction of MTX resistance was 54 per 10(6) cells per Gy. The frequency of drug-resistant cells among individual untreated tumors was highly variable; among individual irradiated tumors the frequency of drug-resistant cells was significantly less variable. These studies provide supporting data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be due to radiation-induced drug resistance

Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs.

Science.gov (United States)

Henderson, Ian; Lavigne, Patrick; Valenzuela, Herminio; Oakes, Barry

2007-02-01

Information regarding the quality of autologous chondrocyte implantation repair is needed to determine whether the current autologous chondrocyte implantation surgical technology and the subsequent biologic repair processes are capable of reliably forming durable hyaline or hyaline-like cartilage in vivo. We report and analyze the properties and qualities of autologous chondrocyte implantation repairs. We evaluated 66 autologous chondrocyte implantation repairs in 57 patients, 55 of whom had histology, indentometry, and International Cartilage Repair Society repair scoring at reoperation for mechanical symptoms or pain. International Knee Documentation Committee scores were used to address clinical outcome. Maximum stiffness, normalized stiffness, and International Cartilage Repair Society repair scoring were higher for hyaline articular cartilage repairs compared with fibrocartilage, with no difference in clinical outcome. Reoperations revealed 32 macroscopically abnormal repairs (Group B) and 23 knees with normal-looking repairs in which symptoms leading to arthroscopy were accounted for by other joint disorders (Group A). In Group A, 65% of repairs were either hyaline or hyaline-like cartilage compared with 28% in Group B. Autologous chondrocyte repairs composed of fibrocartilage showed more morphologic abnormalities and became symptomatic earlier than hyaline or hyaline-like cartilage repairs. The hyaline articular cartilage repairs had biomechanical properties comparable to surrounding cartilage and superior to those associated with fibrocartilage repairs.

What is the role of autologous blood transfusion in major spine surgery?

Science.gov (United States)

Kumar, Naresh; Chen, Yongsheng; Nath, Chinmoy; Liu, Eugene Hern Choon

2012-06-01

Major spine surgery is associated with significant blood loss, which has numerous complications. Blood loss is therefore an important concern when undertaking any major spine surgery. Blood loss can be addressed by reducing intraoperative blood loss and replenishing perioperative blood loss. Reducing intraoperative blood loss helps maintain hemodynamic equilibrium and provides a clearer operative field during surgery. Homologous blood transfusion is still the mainstay for replenishing blood loss in major spine surgery across the world, despite its known adverse effects. These significant adverse effects can be seen in up to 20% of patients. Autologous blood transfusion avoids the risks associated with homologous blood transfusion and has been shown to be cost-effective. This article reviews the different methods of autologous transfusion and focuses on the use of intraoperative cell salvage in major spine surgery. Autologous blood transfusion is a proven alternative to homologous transfusion in major spine surgery, avoiding most, if not all of these adverse effects. However, autologous blood transfusion rates in major spine surgery remain low across the world. Autologous blood transfusion may obviate the need for homologous transfusion completely. We encourage spine surgeons to consider autologous blood transfusion wherever feasible.

Bystander effect in human hepatoma HepG2 cells caused by medium transfers at different times after high-LET carbon ion irradiation

International Nuclear Information System (INIS)

Wu Qingfeng; Li Qiang; Jin Xiaodong; Liu Xinguo; Dai Zhongying

2011-01-01

Although radiation-induced bystander effects have been well documented in a variety of biological systems, whether irradiated cells have the ability to generate bystander signaling persistently is still unclear and the clinical relevance of bystander effects in radiotherapy remains to be elucidated. This study examines tumor cellular bystander response to autologous medium from cell culture irradiated with high-linear energy transfer (LET) heavy ions at a therapeutically relevant dose in terms of clonogenic cell survival. In vitro experiments were performed using human hepatoma HepG2 cell line exposed to 100 keV/μm carbon ions at a dose of 2 Gy. Two different periods (2 and 12 h) after irradiation, irradiated cell conditioned medium (ICCM) and replenished fresh medium were harvested and then transferred to unirradiated bystander cells. Cellular bystander responses were measured with the different medium transfer protocols. Significant higher survival fractions of unirradiated cells receiving the media from the irradiated cultures at the different times post-irradiation than those of the control were observed. Even replenishing fresh medium for unirradiated cells which had been exposed to the ICCM for 12 h could not prevent the bystander cells from the increased survival fraction. These results suggest that the irradiated cells could release unidentified signal factor(s), which induced the increase in survival fraction for the unirradiated bystander cells, into the media sustainedly and the carbon ions triggered a cascade of signaling events in the irradiated cells rather than secreting the soluble signal factor(s) just at a short period after irradiation. Based on the observations in this study, the importance of bystander effect in clinical radiotherapy was discussed and incorporating the bystander effect into the current radiobiological models, which are applicable to heavy ion radiotherapy, is needed urgently.

Regeneration of Tissues and Organs Using Autologous Cells

Energy Technology Data Exchange (ETDEWEB)

Anthony Atala

2010-04-28

The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the cure that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the

Cancer-Associated Fibroblasts from lung tumors maintain their immuno-suppressive abilities after high-dose irradiation

Directory of Open Access Journals (Sweden)

Laia eGorchs

2015-05-01

Full Text Available Accumulating evidence supports the notion that high-dose (>5 Gy radiotherapy (RT regimens are triggering stronger pro-immunogenic effects than standard low-dose (2 Gy regimens. However, the effects of RT on certain immunoregulatory elements in tumors remain unexplored. In this study we have investigated the effects of high-dose irradiation (HD-RT on the immunomodulating functions of cancer-associated fibroblasts (CAFs. Primary CAF cultures were established from lung cancer specimens derived from patients diagnosed for non-small cell lung cancer. Irradiated and non-irradiated CAFs were examined for immunomodulation in experiments with peripheral blood mononuclear cells from random, healthy donors. Regulation of lymphocytes behavior was checked by lymphocyte proliferation assays, lymphocyte migration assays and T-cell cytokine production. Additionally, CAF-secreted immuno-regulatory factors were studied by multiplex protein arrays, ELISAs and by LC-MS/MS proteomics. In all functional assays we observed a powerful immuno-suppressive effect exerted by CAF-conditioned medium on activated T-cells (p>0,001, and this effect was sustained after a single radiation dose of 18 Gy. Relevant immuno-suppressive molecules such as prostaglandin E2, interleukin-6 and -10, or transforming growth factor-β were found in CAF conditioned medium, but their secretion was unchanged after irradiation. Finally, immunogenic cell death responses in CAFs were studied by exploring the release of high motility group box-1 and ATP. Both alarmins remained undetectable before and after irradiation. In conclusion, CAFs play a powerful immuno-suppressive effect over activated T-cells, and this effect remains unchanged after HD-RT. Importantly, CAFs do not switch on immunogenic cell death responses after exposure to HD-RT.

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).

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).

Regulation of tumor invasion by interstitial fluid flow

International Nuclear Information System (INIS)

Shieh, Adrian C; Swartz, Melody A

2011-01-01

The importance of the tumor microenvironment in cancer progression is undisputed, yet the significance of biophysical forces in the microenvironment remains poorly understood. Interstitial fluid flow is a nearly ubiquitous and physiologically relevant biophysical force that is elevated in tumors because of tumor-associated angiogenesis and lymphangiogenesis, as well as changes in the tumor stroma. Not only does it apply physical forces to cells directly, but interstitial flow also creates gradients of soluble signals in the tumor microenvironment, thus influencing cell behavior and modulating cell–cell interactions. In this paper, we highlight our current understanding of interstitial fluid flow in the context of the tumor, focusing on the physical changes that lead to elevated interstitial flow, how cells sense flow and how they respond to changes in interstitial flow. In particular, we emphasize that interstitial flow can directly promote tumor cell invasion through a mechanism known as autologous chemotaxis, and indirectly support tumor invasion via both biophysical and biochemical cues generated by stromal cells. Thus, interstitial fluid flow demonstrates how important biophysical factors are in cancer, both by modulating cell behavior and coupling biophysical and biochemical signals

Radiobiological effect of different irradiation fractionated regimens in human brain glioma

International Nuclear Information System (INIS)

Gai Xue; Yang Weizhi; Gao Li; Jiang Heng; Wang Mianrong; Shi Huizhen

2010-01-01

Objective: To evaluate the radiobiological effect of different irradiation fractionated regimens in human glioma cells (BT 325 cell line). Methods: The xenografts in Balb/c-nude mice were irradiated with different single and fractionated regimens. The single fraction dose was 10, 20, 30, 40 and 60 Gy, respectively. The fractionated regimens were 2 Gy x 5 fractions ( irradiated every day), and 3 Gy x 3 fractions (irradiated every other day), 3 Gy x 5 fractions (irradiated every day) and 4 Gy x 3 fractions (irradiated every other day), with total doses of 125 Gy, 114 Gy, 126 Gy and 112 Gy, respectively. The growth curve was used to evaluate the tumor doubling time. clonogenic assays was performed to draw the cell survival curve and analyze the radiobiological parameters with doses of 1, 2, 4, 6, 8 and 10 Gy. T 1/2 was measured by comet assay. Results: Tumor regression were not observed by single fraction irradiation, 2 Gy x 5 fractions and 3 Gy x 3 fractions irradiation regimens. The tumor regress was more significant with the increas of fraction dose. The 4 Gy x 3 fractions inhibited tumor more though not curing tumor. The cell doubling time of the BT 325 cell was 30. 16 h and the tumor doubling time of the xenograft was 43 days.When fitted with L-Q model, α was 0. 36 Gy -1 and β was 0. 057 Gy -2 . When fitted with the single-hit multi target model, D 0 was 1. 394 Gy, Dq was 2. 127 Gy and SF 2 was 0.714, respectively. The T 1/2 was 9.999 min. Conclusions: Glioma is a radioresistant tumor. Increase of the fraction dose improves recent effect.Further study is needed to control the tumor stem cells. (authors)

Experimental study on anti-tumor effect of pcEgr-IFNγ gene-radiotherapy

International Nuclear Information System (INIS)

Wu Congmei; Li Xiuyi; Liu Shuzheng

2001-01-01

Objective: To study the anti-tumor effect of IFN γ gene-radiotherapy to murine melanoma and its immunologic mechanism. Methods: pcEgr-IFNγ plasmids were injected locally into tumor, and 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different time, IFN γ expression 3 days later and immunologic indexes 15 days later were detected. Results: At 3-15 days after pcEgr-IFNγ gene-radiotherapy, the tumor growth rate was lower than that of irradiation alone group. It was also lower than that of gene therapy alone group and control plasmid combined with X-ray irradiation group significantly. Day 3 tumor IFN γ expression was higher than that of plasmid treatment alone group. NK activity, IL-2 and IFN γ secretion activities were higher than those of gene therapy alone and irradiation alone groups significantly. Conclusion: The antitumor effect of IFN γ gene-radiotherapy is better than that of either of them applied solely. Its mechanism might be concerned with the higher expression of IFN γ induced by irradiation in tumors and activation of anti-tumor immunologic functions

In vitro irradiation system for radiobiological experiments

International Nuclear Information System (INIS)

Tesei, Anna; Zoli, Wainer; D’Errico, Vincenzo; Romeo, Antonino; Parisi, Elisabetta; Polico, Rolando; Sarnelli, Anna; Arienti, Chiara; Menghi, Enrico; Medri, Laura; Gabucci, Elisa; Pignatta, Sara; Falconi, Mirella; Silvestrini, Rosella

2013-01-01

Although two-dimensional (2-D) monolayer cell cultures provide important information on basic tumor biology and radiobiology, they are not representative of the complexity of three-dimensional (3-D) solid tumors. In particular, new models reproducing clinical conditions as closely as possible are needed for radiobiological studies to provide information that can be translated from bench to bedside. We developed a novel system for the irradiation, under sterile conditions, of 3-D tumor spheroids, the in vitro model considered as a bridge between the complex architectural organization of in vivo tumors and the very simple one of in vitro monolayer cell cultures. The system exploits the same equipment as that used for patient treatments, without the need for dedicated and highly expensive instruments. To mimic the passage of radiation beams through human tissues before they reach the target tumor mass, 96-multiwell plates containing the multicellular tumor spheroids (MCTS) are inserted into a custom-built phantom made of plexiglass, the material most similar to water, the main component of human tissue. The system was used to irradiate CAEP- and A549-derived MCTS, pre-treated or not with 20 μM cisplatin, with a dose of 20 Gy delivered in one session. We also tested the same treatment schemes on monolayer CAEP and A549 cells. Our preliminary results indicated a significant increment in radiotoxicity 20 days after the end of irradiation in the CAEP spheroids pre-treated with cisplatin compared to those treated with cisplatin or irradiation alone. Conversely, the effect of the radio- chemotherapy combination in A549-derived MCTS was similar to that induced by cisplatin or irradiation alone. Finally, the 20 Gy dose did not affect cell survival in monolayer CAEP and A549 cells, whereas cisplatin or cisplatin plus radiation caused 100% cell death, regardless of the type of cell line used. We set up a system for the irradiation, under sterile conditions, of tumor cells

Radiation therapy in leukemia (total body irradiation excluded); Irradiations pour leucemie a l`exclusion de l`irradiation corporelle totale

Energy Technology Data Exchange (ETDEWEB)

Peiffert, D.; Hoffstetter, S. [Centre Alexis-Vautrin, 54 - Vandoeuvre-les-Nancy (France). Dept. de Radiotherapie

1999-03-01

Radiation techniques and indications in leukemias have been described in detail, yet prophylactic cranial irradiation in acute leukemia still has few indications. Cerebrospinal and testicular irradiation are reserved for relapsing disease. Radiation usually results in rapid functional improvement when used in neurologic emergencies and symptomatic neurologic or gross tumors relapses. Nevertheless, the improvements recently obtained by systemic chemotherapy have resulted in the reduction in the use of irradiation, especially in children, where it was considered deleterious with neuropsychological sequelae. Splenic irradiation remains useful for symptomatic myelo-proliferative syndrome. (authors)

Life shortening, tumor induction, and tissue dose for fission-neutron and gamma-ray irradiations

International Nuclear Information System (INIS)

Grahn, D.; Duggal, K.; Lombard, L.S.

1985-01-01

The primary focus of this program is to obtain information on the late effects of whole body exposure to low doses of a high linear-energy-transfer (LET) and a low-LET ionizing radiation in experimental animals to provide guidance for the prediction of radiation hazards to man. The information obtained takes the form of dose-response curves for life shortening and for the induction of numerous specific types of tumors. The animals are irradiated with fission neutrons from the Janus reactor and with 60 Co gamma rays, delivered as single, weekly, or duration-of-life exposures covering the range of doses and dose rates. 6 refs

Irradiated large segment allografts in limb saving surgery for extremity tumor - Philippine experience

International Nuclear Information System (INIS)

Wang, E.H.M.; Agcaoili, N.; Turqueza, M.S.

1999-01-01

Limb saving surgery has only recently become an option in the Phillipines. This has given a better comprehension of oncologic principles and from the refinement of bone-reconstruction procedures. Foremost among the latter is the use of large segment bone allografts. Large-segment allografts (LSA) are available from the Tissue and Bone Bank of the University of the Philippines (UP). After harvest, these bones are processed at the Bank, radiation-sterilized at the Philippine Nuclear Research Institute, and then stored in a -80 degree C deep freezer. We present our 4-year experience (Jan 93 - Dec 96) with LSA for limb saving surgery in musculoskeletal tumors. All patients included had: (1) malignant or aggressive extremity tumors; (2) surgery performed by the UP - Musculoskeletal Tumor Unit (UP-MUST Unit); (3) reconstructions utilizing irradiated large-segment allografts from the UP Tissue and Bone Bank; and (4) follow-up of at least one year or until death. Tumors included osteosarcoma (6) giant cell tumors (11), and metastatic lesions (3). Age ranged from 16-64 years old; 13 males and 7 females. Bones involved were the femur (12) tibia (5) and humerus (3). Average defect length was 15 cm and surgeries performed were intercalary replacement (5), resection arthrodesis (11), hemicondylar allograft (3), and allograft-prosthesis-composite (1). Follow-up ranged was from 17- 60 months or until death. Fifteen (1 5) were alive with NED (no evidence of disease), 3 were dead (2 of disease 1 of other causes), and 2 were AWED (alive with evidence of disease). Functional evaluation using the criteria of the International Society of Limb Salvage (ISOLS) was performed on 18 patients. This averaged 27.5 out of 30 points (92%) for 15 patients. Many having returned to their previous work and recreation. The 3 failures were due to infections in 2 cases (both of whom opted for amputations but who have not been fit with prostheses), and a fracture (secondary to a fall) in one case. Limb

Antitumor bystander effect induced by radiation-inducible target gene therapy combined with α particle irradiation

International Nuclear Information System (INIS)

Liu Hui; Jin Chufeng; Wu Yican; Ge Shenfang; Wu Lijun; FDS Team

2012-01-01

In this work, we investigated the bystander effect of the tumor and normal cells surrounding the target region caused by radiation-inducible target gene therapy combined with α-particle irradiation. The receptor tumor cell A549 and normal cell MRC-5 were co-cultured with the donor cells irradiated to 0.5 Gy or the non-irradiated donor cells, and their survival and apoptosis fractions were evaluated. The results showed that the combined treatment of Ad-ET and particle irradiation could induce synergistic antitumor effect on A549 tumor cell, and the survival fraction of receptor cells co-cultured with the irradiated cells decreased by 6%, compared with receptor cells co-cultured with non-irradiated cells, and the apoptosis fraction increased in the same circumstance, but no difference was observed with the normal cells. This study demonstrates that Ad-ET combined with α-particle irradiation can significantly cause the bystander effect on neighboring tumor cells by inhibiting cell growth and inducing apoptosis, without obvious toxicity to normal cells. This suggests that combining radiation-inducible TRAIL gene therapy and irradiation may improve tumor treatment efficacy by specifically targeting tumor cells and even involving the neighboring tumor cells. (authors)

Efficacy of autologous platelets in macular hole surgery.

Science.gov (United States)

Konstantinidis, Aristeidis; Hero, Mark; Nanos, Panagiotis; Panos, Georgios D

2013-01-01

The introduction of optical coherence tomography has allowed accurate measurement of the size of macular holes. A retrospective consecutive review was performed of 21 patients undergoing macular hole repair with vitrectomy, gas tamponade, and autologous platelet injection and we assessed the effect of macular hole parameters on anatomic and functional outcomes. We looked at the demographic features, final visual outcome, and anatomical closure. Twenty-one patients were included in the study. They underwent routine vitrectomy with gas tamponade (C3F8) and injection of autologous platelets. All patients were advised to maintain a facedown posture for 2 weeks. Anatomical closure was confirmed in all cases and 20 out of 21 of patients had improved postoperative visual acuity by two or more lines. In our series, the macular hole dimensions did not have much effect on the final results. The use of autologous platelets and strict facedown posture seems to be the deciding factor in good anatomical and visual outcome irrespective of macular hole dimensions.

Stereotactic irradiation of tumors

International Nuclear Information System (INIS)

Reinbacher, L.

1989-01-01

In the Federal German Cancer Research Center in Heidelberg, a specific brain tumor localization system has been developed. The system offers precise and easy manipulation, and pin-pointed application for diagnostic evaluation and therapy. The radiation source for radiotherapy are 125 J-seeds. The method so far is applied primarily for treatment of astrocytomas in children. The article reviews applications and results. (MG) [de

Repair of potentially lethal damage following irradiation with x rays or cyclotron neutrons: response of the EMT-6/UW tumor system treated under various growth conditions in vitro and in vivo

International Nuclear Information System (INIS)

Rasey, J.S.; Nelson, N.J.

1981-01-01

Postirradiation potentially lethal damage (PLD) repair was examined in the EMT-6/UW tumor system under a variety of in vitro and in vivo growth conditions. Following x irradiation, surviving fraction increased in fed and unfed plateau cultures if subculture and plating were delayed; in exponentially growing cultures if they were covered with depleted medium for the first 6 h postirradiation; and in tumors in vivo if excision for preparation of a cell suspension was delayed. Following irradiation with 21.5 meV (d + → Be) neutrons, PLD repair was measurable only in unfed plateau cultures when subculture was delayed and in exponentially growing cells exposed to depleted culture medium immediately after irradiation. In x-irradiated EMT-6/UW cells, the greatest repair capacity and the highest surviving fraction ratios were measured in unfed plateau cultures; the least repair was observed in exponentially growing cells exposed to depleted medium. Thus post-neutron repair was not limited to situations where the amount of repair of photon PLD is large. The demonstration of PLD repair in tumors irradiated in vivo with X rays and the absence of such repair after neutrons could have important implications in radiotherapy if this is a general phenomenon