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Sample records for implanted vx2 tumour

  1. Percutaneous Ultrasound Guided Implantation of VX2 for Creation of a Rabbit Hepatic Tumor Model

    PubMed Central

    White, Sarah B.; Chen, Jeane; Gordon, Andrew C.; Harris, Kathleen R.; Nicolai, Jodi R.; West, Derek L.; Larson, Andrew C.

    2015-01-01

    Creation of a VX2 tumor model has traditionally required a laparotomy and surgical implantation of tumor fragments. Open surgical procedures are invasive and require long procedure times and recovery that can result in post-operative morbidity and mortality. The purpose of this study is to report the results of a percutaneous ultrasound guided method for creation of a VX2 model in rabbit livers. A total of 27 New Zealand white rabbits underwent a percutaneous ultrasound guided approach, where a VX2 tumor fragment was implanted in the liver. Magnetic resonance imaging was used to assess for tumor growth and necropsy was performed to determine rates of tract seeding and metastatic disease. Ultrasound guided tumor implantation was successful in all 27 rabbits. One rabbit died 2 days following the implantation procedure. Two rabbits had no tumors seen on follow-up imaging. Therefore, tumor development was seen in 24/26 (92%) rabbits. During the follow-up period, tract seeding was seen in 8% of rabbits and 38% had extra-hepatic metastatic disease. Therefore, percutaneous ultrasound guided tumor implantation safely provides reliable tumor growth for establishing hepatic VX2 tumors in a rabbit model with decreased rates of tract seeding, compared to previously reported methods. PMID:25853660

  2. FDG-MicroPET and Diffusion-Weighted MR Image Evaluation of Early Changes After Radiofrequency Ablation in Implanted VX2 Tumors in Rabbits

    SciTech Connect

    Ohira, Tomohiro Okuma, Tomohisa; Matsuoka, Toshiyuki; Wada, Yasuhiro; Nakamura, Kenji; Watanabe, Yasuyoshi; Inoue, Yuichi

    2009-01-15

    The objective of this study was to evaluate the early changes after radiofrequency ablation (RFA) in VX2 rabbit tumors implanted into the back muscles by diffusion-weighted magnetic resonance (MR) imaging and {sup 18}F-2-fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG PET). Percutaneous CT-guided RFA was conducted in seven rabbits with implanted VX2 tumors. VX2 tumors on the other side were untreated and served as the control. MR imaging was performed with a clinical 1.5-T instrument 2 days after RFA, and FDG-PET, using a high-resolution PET scanner for small animals, was obtained 3 days after the procedure. The mean apparent diffusion coefficient (ADC) values and radioactivity count of untreated and ablated tumors were calculated. Untreated VX2 tumors showed hyperintensity on T1-, T2-, and diffusion-weighted MR images, ring-enhanced on contrast-enhanced T1-weighted imaging, and ring-shaped FDG accumulation on FDG-PET. Ablated VX2 tumors showed slight hyperintensity on T1-, T2-, and diffusion-weighed images, slight enhancement on contrast-enhanced T1-weighted images, and low accumulation on FDG-PET. The ADC value of ablated VX2 tumors (1.52 {+-} 0.24 x 10{sup -3} mm{sup 2}/s) was significantly higher than that of untreated tumors (1.09 {+-} 0.12 x 10{sup -3}; p < 0.05). The tumor/muscle ratio of ablated tumors (0.5 {+-} 0.3) was significantly lower than that of untreated tumors (11.6 {+-} 3.2; p < 0.05). Histopathological examination confirmed the lack of viable tumor cells in the ablated lesions. The results indicate that both ADC value and FDG-PET are potentially useful markers for monitoring the early effects of RFA.

  3. Role of MR-DWI and MR-PWI in the radiotherapy of implanted pulmonary VX-2 carcinoma in rabbits

    PubMed Central

    Zhang, Mingmin; Liu, Zhaoxin; Shi, Baoqi; Qi, Fuliang; Wang, Haijiang; Lv, Yuan; Jin, Haijiao; Zhang, Weijing

    2014-01-01

    Objective To detect the activity of tumor cells and tumor blood flow before and after the radiotherapy of implanted pulmonary VX-2 carcinoma in rabbit models by using magnetic resonance diffusion-weighted imaging (MR-DWI) and magnetic resonance perfusion weighted imaging (MR-PWI), and to evaluate the effectiveness and safety of the radiotherapy based on the changes in the MR-DWI and MR-PWI parameters at different treatment stages. Methods A total of 56 rabbit models with implanted pulmonary VX-2 carcinoma were established, and then equally divided into treatment group and control group. MR-DWI and MR-PWI were separately performed using a Philips Acheiva 1.5T MRI machine (Philips, Netherland). MRI image processing was performed using special perfusion software and the WORKSPACE advanced workstation for MRI. MR-DWI was applied for the observation of tumor signals and the measurement of apparent diffusion coefficient (ADC) values; whereas MR-PWI was used for the measurement of wash in rate (WIR), wash out rate (WOR), and maximum enhancement rate (MER). The radiation treatment was performed using Siemens PRIMUS linear accelerator. In the treatment group, the radiotherapy was performed 21 days later on a once weekly dosage of 1,000 cGy to yield a total dosage of 5,000 cGy. Results The ADC parameters in the region of interest on DWI were as follows: on the treatment day for the implanted pulmonary VX-2 carcinoma, the t values at the center and the edge of the lesions were 1.352 and 1.461 in the treatment group and control group (P>0.05). During weeks 0-1 after treatment, the t values at the center and the edge of the lesions were 1.336 and 1.137 (P>0.05). During weeks 1-2, the t values were 1.731 and 1.736 (P<0.05). During weeks 2-3, the t values were 1.742 and 1.749 (P<0.05). During weeks 3-4, the t values were 2.050 and 2.127 (P<0.05). During weeks 4-5, the t values were 2.764 and 2.985 (P<0.05). The ADC values in the treatment group were significantly higher than in

  4. Dynamic Evolutionary Changes in Blood Flow Measured by MDCT in a Hepatic VX2 Tumor Implant over an Extended 28-day Growth Period: Time-Density Curve Analysis1

    PubMed Central

    Wu, Hanping; Exner, Agata A.; Shi, Hong; Bear, Joshua; Haaga, John R.

    2012-01-01

    Rationale and Objectives The enhancement pattern of malignant tumors has been studied in short-term animal models (7–14 days), but the reported results have been variable and inconsistent. The purpose of this study was to investigate the changing blood flow characteristics of VX2 tumors implanted in rabbit livers with contrast-enhanced multidetector computed tomography (MDCT) to establish a predictable pattern of vascular evolution over an extended 28-day growth period. Materials and Methods VX2 carcinoma was implanted in livers of 10 male New Zealand White rabbits. Dynamic CT (2/seconds × 60 seconds) was conducted on days 7, 14, 21, and 28 after tumor implantation. Enhancement parameters of time-density curve (TDC), time to start (T0), time to peak (TP), maximum enhancement (ΔH), slope of enhancement (SLe), and washout (SLw) in tumor center, tumor rim, and normal liver were analyzed. Tumor samples corresponding to CT images of one tumor on days 14 and 21 and seven tumors on day 28 were stained with hematoxylin and eosin and anti-CD31 monoclonal antibody. The relationship between enhancement parameters and histology parameters (thickness of tumor border, extent of blood stasis, and luminar vessel density) was analyzed. Results Consistent growth, appearance, and vascular changes occurred in 7 of 10 animals over the 4-week observation period. Peripheral rim-like enhancement was noted in CT images. TDC analysis showed that tumor rim enhancement was pronounced and more rapid than normal liver initially but this difference diminished with tumor progression. The SLe, SLw, and ΔH decreased from 10.03 ± 3.25 Hu/second, 0.42 ± 0.25 Hu/sec, and 58.00 ± 25.27 Hu on day 7 to 5.86 ± 2.73 Hu/second, 0.10 ± 0.13 Hu/second, and 37.78 ± 8.89 Hu/second on day 28, respectively. TP increased from 12.71 ± 4.85 seconds on day 7 to 25.57 ± 7.75 seconds on day 28. No significant changes were noted on the TDC parameters in normal liver. The maximum density difference between

  5. Evaluation of a rabbit rectal VX2 carcinoma model using computed tomography and magnetic resonance imaging

    PubMed Central

    Liang, Xin-Mei; Tang, Guang-Yu; Cheng, Ying-Sheng; Zhou, Bi

    2009-01-01

    AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma. METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to observe tumor growth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded. RESULTS: Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density foci of the tumor in the rectum wall, while enhanced CT scanning demonstrated asymmetrical intensification in tumor foci. MRI scanning showed a low signal of the tumor on T1-weighted imaging and a high signal of the tumor on T2-weighted imaging. Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could be observed 6 wk after VX2 cell implantation, and a large area of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation. CONCLUSION: The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma. PMID:19418587

  6. Characteristics of liver on magnetic resonance diffusion-weighted imaging: Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

    PubMed Central

    Yuan, You-Hong; Xiao, En-Hua; Liu, Jian-Bin; He, Zhong; Jin, Ke; Ma, Cong; Xiang, Jun; Xiao, Jian-Hua; Chen, Wei-Jian

    2008-01-01

    AIM: To investigate dynamical and image pathological characteristics of the liver on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model. METHODS: Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1- and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21th d. Ten VX-2 tumor samples were studied pathologically. RESULTS: The rate of lump detected by DWI, T1WI and T2WI was 78.7%, 10.7% and 53.5% (χ2 = 32.61, P < 0.001) on the 7th d after implantation and 95.8%, 54.3% and 82.9% (χ2 = 21.50, P < 0.001) on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not decrease on the 7th d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21th d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually

  7. Histotripsy and metastasis: Assessment in a renal VX-2 rabbit tumor model

    NASA Astrophysics Data System (ADS)

    Styn, Nicholas R.; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2012-10-01

    Histotripsy is a non-invasive, pulsed ultrasound technology where controlled cavitation is used to homogenize targeted tissue. We sought to assess the possibility that histotripsy may increase metastatic spread of tumor by quantifying the number of lung metastasis apparent after histotripsy treatment of aggressive renal VX-2 tumor compared to nontreated controls. VX-2 tumor was implanted in the left kidneys of 28 New Zealand White rabbits. Twenty rabbits were treated with histotripsy (day 13 after implantation) while 8 served as controls. All rabbits underwent left nephrectomy (day 14) and then were euthanized (day 19). This study was powered to detect a doubling in metastatic rate. Homogenized tumor was seen in all treated nephrectomy specimens. Whole-mount, coronal lung sections were viewed to calculate number and density of metastases. Viable tumor was present in all 28 lungs examined. Histology confirmed fractionation of tumor in all treatment rabbits. There was not a statistical difference in total lung metastases (88.7 vs. 72.5; p=0.29) or metastatic density (8.9 vs. 7.0 mets/cm2; p=0.22) between treated and control rabbits. Further investigation is planned to validate these results in the VX-2 model and to assess metastatic rates in less aggressive tumors treated with histotripsy.

  8. Hepatic arterial administration of sorafenib and iodized oil effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX2 hepatocellular carcinoma model

    PubMed Central

    Zhang, Lin; Liu, Feng-Yong; Fu, Jin-Xin; Duan, Feng; Fan, Qing-Sheng; Wang, Mao-Qiang

    2014-01-01

    Aim: To investigate the therapeutic effect of the hepatic arterial administration of sorafenib in rabbit VX-2 hepatocellular carcinoma (HCC) model. Methods: Rabbit VX-2 HCC models were established via implanting VX-2 tumors into the livers, and randomly divided into four groups, respectively treated with (1) The hepatic arterial administration of iodized oil alone (TACE-i), (2) The hepatic arterial administration of iodized oil and pharmorubicin (TACE-ip), (3) The hepatic arterial administration of iodized and cis-DDP (TACE-ic), (4) The hepatic arterial administration of iodized and sorafenib (TACE-is). The growth rate and intrahepatic metastasis of implanted VX-2 tumor in each rabbit were measured. Microvessel density (MVD) in the adjacent tissues of implanted VX-2 tumor were estimated by detecting the expression of CD34 and VEGF level in tumor adjacent tissues were also examined by Immunohistochemistry. Results: Compared with other groups, TACE-is treatment group presented a better effect on inhibiting tumor growth rate and intrahepatic metastasis in rabbit VX-2 HCC model. The angiogenesis (assessed by MVD) in the adjacent tissues were suppressed more dramatically in TACE-is treated group. Moreover, TACE-is treatment did not significantly increase the levels of alanine transaminase and creatinine compared to the group with TACE-i treatment. Conclusion: The hepatic arterial administration of sorafenib and iodized oil (TACE-is) effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX-2 HCC model without obvious hepatic and renal toxicity. One of the related mechanisms may be due to the inhibition of angiogenesis in the adjacent tissues. Our data indicated that TACE-is may be a secure and effective treatment for HCC. PMID:25550815

  9. Effects of tumour cells on angiogenesis and vasoconstrictor responses in sponge implants in mice.

    PubMed

    Andrade, S P; Bakhle, Y S; Hart, I; Piper, P J

    1992-11-01

    The effects of tumour cells (Colon 26) on the development and response of new blood vessels to different vasoconstrictors (platelet activating factor; PAF, endothelin-1, angiotensin II, adrenalin and 5-hydroxytryptamine) have been investigated. Sponge implants in mice were used to host tumour cells while washout of 133Xe was employed to assess local blood flow in the implanted sponges. By 14 days after implantation the response of vessels in tumour-bearing implants to the various vasoconstrictors generally was decreased compared to that obtained in control sponge implants or adjacent normal skin. Thus at this time point the t1/2 for 133Xe washout from control sponges treated with adrenalin (0.5 micrograms) was 30 +/- 4 min whereas in tumour-bearing sponges it was 5 +/- 1 min. This decreased sensitivity in tumour vessels was probably not due to a complete lack of contractile elements since actin was demonstrated by immunohistochemistry around blood vessels in both types of implant. The results of the present study have shown that the pharmacological responses of blood vessels in a growing tumour, Colon 26, differed from the responses of vessels of a similar age in non-neoplastic tissue. These results appear to suggest that the different angiogenic stimuli released from tumour tissue may markedly influence pharmacological reactivity of newly formed blood vessels. PMID:1384642

  10. The Primary Implantation of Human Tumours to the Hamster Cheek Pouch

    PubMed Central

    Williams, Dorothy E.; Evans, D. M. D.; Blamey, R. W.

    1971-01-01

    The hamster cheek pouch is an immunologically privileged site. The present study is of simple implantation of human tumours direct from operative specimen to cheek pouch, in particular to determine whether tumour type influences the rate of successful implant. All implants were studied 10 or 20 days later. The use of cortisone significantly improved the number of implants growing. Carcinomas of the cervix were found to show growth in 55% of implants, in animals conditioned with cortisone. Growth from tumours of the uterine body, or from colorectal carcinomas, occurred in 25-30% of implants. Breast cancer gave poor results. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:5144526

  11. Dynamical Observation on Biological Progression of VX2 Liver Tumors to Identify the Optimal Time for Intervention in Animal Models

    PubMed Central

    Wang, Zhenguang; Yang, Guangjie; Nie, Pei; Fu, Junhua; Wang, Xufu; Liu, Dan

    2013-01-01

    Purpose Based on practice guideline of “management of hepatocellular carcinoma (HCC): update” published by American Association for the Study of Liver Diseases (AASLD) and “Barcelona Clinic Liver Cancer staging system (BCLC),” this study investigated how to enroll the optimal VX2 liver tumor model for HCC researches by dynamically observing the biological progression of the tumor. Materials Thirty-two healthy New Zealand white rabbits were implanted VX2 liver tumor by cell suspension method (n=24) and tissue fragment method (n=8). All the rabbits underwent CT scans on day 7, 14, 21 and 28 after implantation to observe the size of the tumors, the time when metastases and ascites occurred and the survival time. Appropriate intervention times were estimated corresponding to different clinical HCC stages by using tumor diameter-time curve. Results The VX2 liver tumors grew rapidly within 28 days after implantation. And the tumors in the cell suspension group grew faster than those of the tissue fragment group. The appropriate intervention time corresponding to very early stage, early stage and intermediate stage were <11 days, 11–16.9 days and >16.9 days, respectively in the cell suspension group, and <19.9 days, 19.9–25.5 days and >25.5 days, respectively in the tissue fragment group. Conclusion Preclinical animal research needs to improve on different levels to yield best predictions for human patients. Researchers should seek for an individualized proposal to select optimal VX2 liver tumor models for their experiments. This approach may lead to a more accurate determination of therapeutic outcomes. PMID:23977399

  12. Terahertz spectroscopic imaging of a rabbit VX2 hepatoma model

    NASA Astrophysics Data System (ADS)

    Park, Jae Yeon; Choi, Hyuck Jae; Cho, Kyoung-Sik; Kim, Kyu-Rae; Son, Joo-Hiuk

    2011-03-01

    Terahertz (THz) spectroscopic imaging technique was applied to classify the tumor region in the rabbit liver with VX2 hepatocellular carcinoma. Within the measurement range of 0.1-2 THz, the average reflectance values for all tumor samples were more than 4% higher than those for healthy cells, and the terahertz measurements correlated well with histological analysis results. This study on paraffin-embedded tissues showed the alteration of cell density and protein content in tumors, excluding the effect of water.

  13. Focused ultrasound treatment of VX2 tumors controlled by local harmonic motion

    NASA Astrophysics Data System (ADS)

    Curiel, Laura; Huang, Yuexi; Vykhodtseva, Natalia; Hynynen, Kullervo

    2009-06-01

    The purpose of this study was to evaluate the feasibility of using localized harmonic motion (LHM) to monitor and control focused ultrasound surgery (FUS) in VX2 tumors in vivo. FUS exposures were performed on 13 VX2 tumors implanted in nine rabbits. The same transducer induced coagulation and generated a localized oscillatory motion by periodically varying the radiation force. A separate diagnostic ultrasound transducer tracked motion by cross-correlating echo signals at different instances. A threshold in motion amplitude was instituted to cease exposure. Coagulation was confirmed by T2-weighted MR images, thermal dose obtained through MR thermometry and histological examinations. For tumor locations achieving coagulation, the LHM amplitude was 9% (p = 0.04) to 57% (p < 0.0001) lower than that before exposure. Control was successful for 74 (69%) out of 108 cases, with 52 (48%) reaching the threshold and achieving coagulation and 22 (21%) never reaching threshold nor coagulating. For the 34 (31%) unsuccessful exposures, 16 (15%) never reached the threshold but coagulation occurred, and 18 (16%) reached threshold without coagulation confirmed. Noise or radio-frequency signal changes explained motion over- or underestimation in 24 (22%) cases; the remaining 10 (9%) had other causes of error. The control was generally successful, but sudden change or noise in the acquired echo signal caused failure. Coagulation after exposure could be validated by comparing amplitudes before and after exposure.

  14. Intraarterial versus intravenous adriamycin in the rabbit Vx-2 tumor system

    SciTech Connect

    Swistel, A.J.; Bading, J.R.; Raaf, J.H.

    1984-03-15

    Intraarterial (IA) chemotherapy can theoretically result in a high tissue level of the drug with reduced systemic toxicity compared with intravenous (IV) administration. The authors compared these two modes of therapy using Adriamycin (doxorubicin) in the rabbit Vx-2 tumor system. Vx-2 implanted in hind limb muscle, and silastic catheters were placed in the jugular vein and femoral artery. Nuclear imaging of technetium-99m-labeled autologous erythrocytes in nine animals was used to measure the kinetics of tumor blood flow. Presence of tumor increased flow through the involved limb up to threefold. One minute following injection there was no difference in concentration of /sup 99m/Tc in tumor whether labeled cells were introduced IA or IV. Twelve rabbits received IA or IV Adriamycin (3 mg/kg), while eight animals received normal saline IA or IV as controls. Tumor progressed in all control rabbits, whereas there was an objective or complete response in 83% of animals receiving adriamycin. One hundred percent of those treated IA responded compared with 67% for IV. Median time to initial response in animals treated IA was 7 days versus 21 days for those treated IV. Thus, IA Adriamycin achieves a more complete and more rapid response than the drug given IV. This occurs despite a large tumor blood flow and rapid equilibrium using both methods.

  15. Angiogenesis dependent characteristics of tumor observed on rabbit VX2 hepatic carcinoma

    PubMed Central

    Guan, Liming

    2015-01-01

    Objective: To evaluate angiogenesis dependent characteristics of carcinoma proliferation, metastasis and to found if there is tumor vascularity architecture defect. Methods: 36 rabbits were random divided into 2 groups: Experimental group: 18 rabbits liver were implanted with VX2 tumor by surgery operation; Control group: 18 experimental rabbits performed the same surgery operation without tumor implantation, the course of tumor growth and blood vessel invasion was observed by autopsy. One slide was used for hematoxylin-eosin (HE) staining, one slide was used for elastic fiber staining by Victoria blue and Ponceau’s histochemical staining, and one slide was used for vascular endothelial cell immunohistochemical staining with biotinylated-ulex europaeus agglutinin I (UEA I); all three slides were observed under an optical microscopic. One additional slide was systematically observed by electron microscopy. SPSS 19.0 software was used for the statistical analyses of the data. Results: The tumor grew acceleration after tumor angiogenesis, volume of original tumors was correlated with vascular caliber. The central tumor found necrosis without enough blood supply while tumor grew rapidly after tumor angiogenesis. The tumor infiltrated into liver blood sinus, blood vessels in hepatic interstitial tissue, the liver capsular vein and important organs metastasis such as lungs, kidneys, abdominal cavity caused rabbits died. The average vascular density count of 18 experimental rabbits under 400 times light microscope were 43.17 ± 8.68/vessels/High Power Field; Tumor vascular diameter all within 200 μm. Vascular elastic fiber staining presented tumor blood vessels internal, external elastic plate intact, vascular endothelial cells organelles of tumor were integrity without endothelial cells architecture defect found by pathologic observation. Conclusion: Proliferation and metastasis of rabbit VX2 hepatic carcinoma was correlated with tumor angiogenesis and no tumor

  16. Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

    PubMed Central

    Ibarra, R.; Dazard, J-E.; Sandlers, Y.; Rehman, F.; Abbas, R.; Kombu, R.; Zhang, G-F.; Brunengraber, H.; Sanabria, J.

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+/LG−). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using principal component analysis (PCA) and a mixed-effect two-way ANOVA model. Results. Animals recovered from surgery uneventfully. Analyses identified a metabolite profile that significantly differs in experimental conditions after controlling the False Discovery Rate (FDR). 16 metabolites concentrations differed significantly when comparing samples from (LT+/LT−) to samples from (LG+/LG−) livers. A significant difference was also shown in 20 metabolites when comparing samples from (LT+) liver lobes to samples from (LT−) liver lobes. Conclusion. Normal liver tissue harboring malignancy had a distinct metabolic signature. The role of metabolic profiles on liver biopsies for the detection of early liver cancer remains to be determined. PMID:24723740

  17. Intraprocedural Diffusion-Weighted PROPELLER MRI to Guide Percutaneous Biopsy Needle Placement within Rabbit VX2 Liver Tumors

    PubMed Central

    Deng, Jie; Virmani, Sumeet; Yang, Guang-Yu; Tang, Richard; Woloschak, Gayle; Omary, Reed A.; Larson, Andrew C.

    2010-01-01

    Purpose To test the hypothesis that diffusion-weighted (DW)-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) magnetic resonance imaging (MRI) can be used to guide biopsy needle placement during percutaneous interventional procedures to selectively target viable and necrotic tissues within VX2 rabbit liver tumors. Materials and Methods Our institutional Animal Care and Use Committee approved all experiments. In six rabbits implanted with 15 VX2 liver tumors, baseline DWPROPELLER images acquired prior to the interventional procedure were used for apparent diffusion coefficient (ADC) measurements. Next, intraprocedural DW-PROPELLER scans were performed with needle position iteratively adjusted to target viable, necrotic, or intermediate border tissue regions. DW-PROPELLER ADC measurements at the selected needle tip locations were compared with the percentage of tumor necrosis qualitatively assessed at histopathology. Results DW-PROPELLER images demonstrated intratumoral tissue heterogeneity and clearly depicted the needle tip position within viable and necrotic tumor tissues. Mean ADC measurements within the region-of-interest encompassing the needle tip were highly correlated with histopathologic tumor necrotic tissue assessments. Conclusion DW-PROPELLER is an effective method to selectively position the biopsy needle tip within viable and necrotic tumor tissues. The DW-PROPELLER method may offer an important complementary tool for functional guidance during MR-guided percutaneous procedures. PMID:19629976

  18. Focused Ultrasound Surgery Control Using Local Harmonic Motion: VX2 Tumor Study

    NASA Astrophysics Data System (ADS)

    Curiel, Laura; Chopra, Rajiv; Goertz, David; Hynynen, Kullervo

    2009-04-01

    The objective of this study was to develop a real-time method for controlling focused ultrasound surgery using ultrasound imaging. The approach uses measurements of localized harmonic motion (LHM) in order to perform controlled FUS exposures by detecting changes in the elastic properties of tissues during coagulation. Methods: Nine New Zealand rabbits with VX2 tumors implanted in the thigh were used for this study. LHM was generated within the tumors by periodic induction of radiation force using a FUS transducer (80-mm focal length, 100-mm diameter, 20-mm central hole, 1.485-MHz). Tissue motion was tracked by collecting and cross-correlating RF signals during the motion using a separate diagnostic transducer (3-kHz PRF, 5-MHz). After locating the tumor in MR images, a series of sonications were performed to treat the tumors using a reduction in LHM amplitude to control the exposure. Results: LHM was successfully used to control the sonications. A LHM amplitude threshold value was determined at which changes were considered significant and then the exposure was started and stopped when the LHM amplitude dropped below the threshold. The appearance of a lesion was then verified by MRI. The feasibility of LHM measurements to control FUS exposure was validated.

  19. Focused Ultrasound Surgery Control Using Local Harmonic Motion: VX2 Tumor Study

    SciTech Connect

    Curiel, Laura; Chopra, Rajiv; Goertz, David; Hynynen, Kullervo

    2009-04-14

    The objective of this study was to develop a real-time method for controlling focused ultrasound surgery using ultrasound imaging. The approach uses measurements of localized harmonic motion (LHM) in order to perform controlled FUS exposures by detecting changes in the elastic properties of tissues during coagulation. Methods: Nine New Zealand rabbits with VX2 tumors implanted in the thigh were used for this study. LHM was generated within the tumors by periodic induction of radiation force using a FUS transducer (80-mm focal length, 100-mm diameter, 20-mm central hole, 1.485-MHz). Tissue motion was tracked by collecting and cross-correlating RF signals during the motion using a separate diagnostic transducer (3-kHz PRF, 5-MHz). After locating the tumor in MR images, a series of sonications were performed to treat the tumors using a reduction in LHM amplitude to control the exposure. Results: LHM was successfully used to control the sonications. A LHM amplitude threshold value was determined at which changes were considered significant and then the exposure was started and stopped when the LHM amplitude dropped below the threshold. The appearance of a lesion was then verified by MRI. The feasibility of LHM measurements to control FUS exposure was validated.

  20. Delayed and Aberrant Presentation of VX2 Carcinoma in a Rabbit Model of Hepatic Neoplasia.

    PubMed

    Hansen, Sarah A; Fink, Michael K; Upendran, Anandhi; Besch-Williford, Cynthia L; Livingston, Robert S; Amos-Landgraf, James M; Lattimer, Jimmy C; Kannan, Raghuraman

    2015-10-01

    A socially-housed New Zealand white rabbit presented with a large subcutaneous mass on the ventral thorax approximately 11 mo after the intrahepatic delivery of a suspension of VX2 carcinoma cells to induce hepatocellular carcinoma as part of a nanoparticle study. The mass and closely associated axillary lymph node were removed en bloc. Immunohistochemical staining identified the mass as an undifferentiated carcinoma. The rabbit demonstrated no appreciable pathology at the study end point at 16 mo after VX2 inoculation. An additional rabbit from the same VX2 injection cohort was found at necropsy to have an unanticipated intraabdominal mass, also identified as an undifferentiated carcinoma. This case report summarizes the molecular analysis of both tumors through a novel PCR assay, which identified the delayed and aberrant onset of VX2 carcinoma in an extended timeframe not previously reported. PMID:26473347

  1. Delayed and Aberrant Presentation of VX2 Carcinoma in a Rabbit Model of Hepatic Neoplasia

    PubMed Central

    Hansen, Sarah A; Fink, Michael K; Upendran, Anandhi; Besch-Williford, Cynthia L; Livingston, Robert S; Amos-Landgraf, James M; Lattimer, Jimmy C; Kannan, Raghuraman

    2015-01-01

    A socially-housed New Zealand white rabbit presented with a large subcutaneous mass on the ventral thorax approximately 11 mo after the intrahepatic delivery of a suspension of VX2 carcinoma cells to induce hepatocellular carcinoma as part of a nanoparticle study. The mass and closely associated axillary lymph node were removed en bloc. Immunohistochemical staining identified the mass as an undifferentiated carcinoma. The rabbit demonstrated no appreciable pathology at the study end point at 16 mo after VX2 inoculation. An additional rabbit from the same VX2 injection cohort was found at necropsy to have an unanticipated intraabdominal mass, also identified as an undifferentiated carcinoma. This case report summarizes the molecular analysis of both tumors through a novel PCR assay, which identified the delayed and aberrant onset of VX2 carcinoma in an extended timeframe not previously reported. PMID:26473347

  2. Treatment precision of image-guided liver SBRT using implanted fiducial markers depends on marker-tumour distance

    NASA Astrophysics Data System (ADS)

    Seppenwoolde, Y.; Wunderink, W.; Wunderink-van Veen, S. R.; Storchi, P.; Méndez Romero, A.; Heijmen, B. J. M.

    2011-09-01

    The purpose of this study is to assess the accuracy of day-to-day predictions of liver tumour position using implanted gold markers as surrogates and to compare the method with alternative set-up strategies, i.e. no correction, vertebrae and 3D diaphragm-based set-up. Twenty patients undergoing stereotactic body radiation therapy (SBRT) with abdominal compression for primary or metastatic liver cancer were analysed. We determined the day-to-day correlation between gold marker and tumour positions in contrast-enhanced CT scans acquired at treatment preparation and before each treatment session. The influence of marker-tumour distance on the accuracy of prediction was estimated by introducing a method extension of the set-up error paradigm. The distance between gold markers and the centre of the tumour varied between 5 and 96 mm. Marker-guidance was superior to guiding treatment using other surrogates, although both the random and systematic components of the prediction error SD depended on the tumour-marker distance. For a marker-tumour distance of 4 cm, we observed σ = 1.3 mm and Σ = 1.6 mm. The 3D position of the diaphragm dome was the second best predictor. In conclusion, the tumour position can be predicted accurately using implanted markers, but marker-guided set-up accuracy decreases with increasing distance between implanted markers and the tumour.

  3. Assessment of hepatic VX2 tumors with combined percutaneous transhepatic lymphosonography and contrast-enhanced ultrasonographic imaging

    PubMed Central

    Liu, Cun; Liang, Ping; Wang, Yang; Zhou, Pei; Li, Xin; Han, Zhi-Yu; Liu, Shao-Ping

    2008-01-01

    AIM: To evaluate the feasibility and efficacy of percutaneous transhepatic lymphosonography (PTL) as a novel method for the detection of tumor lymphangiogenesis in hepatic VX2 of rabbits and to evaluate combined PTL and routine contrast-enhanced ultrasonographic imaging for the diagnosis of liver cancer. METHODS: Ten rabbits with VX2 tumor were included in this study. SonoVue (0.1 mL/kg) was injected into each rabbit via an ear vein for contrast-enhanced ultrasonographic imaging, and 0.5 mL SonoVue was injected into the normal liver parenchyma near the VX2 tumor for PTL. Images and/or movie clips were stored for further analysis. RESULTS: Ultrasonographic imaging showed VX2 tumors ranging 5-19 mm in the liver of rabbits. The VX2 tumor was hyperechoic and hypoechoic to liver parenchyma at the early and later phase, respectively. The hepatic lymph vessels were visualized immediately after injection of contrast medium and continuously visualized with SonoVue® during PTL. The boundaries of VX2 tumors were hyperechoic to liver parenchyma and the tumors. There was a significant difference in the values for the boundaries of VX2 tumors after injection compared with the liver normal parenchyma and the tumor parenchyma during PTL. CONCLUSION: PTL is a novel method for the detection of tumor lymphangiogenesis in hepatic VX2 of rabbits. Combined PTL and contrast-enhanced ultrasonographic imaging can improve the diagnosis of liver cancer. PMID:18609718

  4. Augmentation of Chemotherapeutic Infusion Effect by TSU-68, an Oral Targeted Antiangiogenic Agent, in a Rabbit VX2 Liver Tumor Model

    SciTech Connect

    Kim, Hyo-Cheol; Chung, Jin Wook Choi, Seung Hong; Im, Seock-Ah; Yamasaki, Yasundo; Jun, Suryoung; Jae, Hwan Jun; Park, Jae Hyung

    2012-02-15

    Purpose: This study was designed to investigate the in vivo effects of combination therapy with TSU-68 and chemotherapeutic infusion in a rabbit VX2 liver tumor model. Methods: This study was approved by the animal care committee at our institute. Three weeks before chemotherapeutic infusion, VX2 carcinoma was implanted into the livers of 32 rabbits. One week after chemotherapeutic infusion, vehicle was administered orally for 3 weeks in the control group (n = 16), and TSU-68 was administered orally at a daily dose of 200 mg/kg for 3 weeks in the treated group (n = 16). Computed tomography (CT) was performed before and 1, 2, 3, and 4 weeks after chemotherapeutic infusion. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) on CT scan. The maximum thickness of viable tumor was measured on microscopic sections. Results: According to the RECIST, stable disease was observed in 9 (56%) rabbits and progressive disease in 7 (44%) in the control group, whereas partial response was observed in 1 (6%) rabbit and stable disease in 15 (94%) in the treated group. On pathologic examination, a viable lesion was present in 12 (75%) rabbits in the control group and in 6 (38%) rabbits in the treated group (P = 0.073). The mean maximum thickness of viable tumor in the treated group was significantly smaller than that in the control group (0.74 mm vs. 3.39 mm; P = 0.02). Conclusions: Oral administration of TSU-68 augmented the effect of chemotherapeutic infusion in a rabbit VX2 liver tumor model.

  5. Feedback control of temperature evolution in rabbit kidney in vivo using MRI guided focused ultrasound. Application to renal VX2 carcinoma ablation

    NASA Astrophysics Data System (ADS)

    Delemazure, A. S.; Salomir, R.; Grenier, N.; Palussière, J.; Deminière, C.; Mougenot, C.; Moonen, C. W.

    2005-03-01

    A significant number of patients with small renal tumours may get benefit from in situ thermo-ablation techniques. Focused ultrasound is a non-invasive approach which offers excellent flexibility. On the other hand, real time MR thermometry is a valuable tool for monitoring and controlling therapy. In this study, coupling of focused ultrasound with PRF-based, respiratory-gated MR thermometry was used to provide temperature feedback control for local hyperthermia in the rabbit kidney. Two heating protocols were initially used in healthy kidneys (medulla and cortex): 1. fixed focal point heating; 2. spiral trajectories of the focal point. Further, five VX2 renal carcinomas were treated with multiple focal point heating in each tumour. Post-treatment MRI follow up and post mortem histology were performed. The shape and size of the lesions (MRI, histology) were compared to the calculated thermal dose map. The standard deviation of the MR thermometry ranged from 0.5°C to 1°C. The temperature controller matched the objective curve with approximately 1°C precision (fixed focal point mode). Several technical and physiological difficulties for spiral heating could not be overcome with the available setup. Thermal ablation with temperature feedback control in healthy and tumour bearing kidney was demonstrated to be feasible and effective, despite specific challenges (deep seated organ, respiratory motion, high blood perfusion).

  6. Indirect computed tomography lymphography identifies lymph node metastasis in rabbit pyriform sinus VX2 carcinoma

    PubMed Central

    SHEN, NA; XU, XIUYIN; SHA, YAN; WU, HAITAO

    2015-01-01

    Indirect computed tomography lymphography (CT-LG) could be used to determine the regional spread of cancer and assess lymphatic function by the interstitial delivery of diagnostic agents. Few studies have been reported on its use in pyriform sinus carcinoma. The aim of the present study was to establish the rabbit VX2 tumor as a model for pyriform sinus carcinoma and to observe its neck lymph node metastasis by indirect CT-LG. VX2 tumor tissue suspension was transplanted into the pyriform sinus submucosa of 15 rabbits under direct laryngoscope. Rabbits were randomly placed into one of three groups, each comprised of five rabbits. Observation of the tumor growth and neck lymph node metastases were taken on days 14 (group 1), 21 (group 2) and 28 (group 3) following transplantation using the method of indirect CT-LG. VX2 tumors were transplanted successfully in all rabbits. Deep cervical lymph nodes were enhanced clearly in indirect CT-LG. The contrast agent filling defected appeared on the metastasis nodes while the lymph node without metastasis was smooth. The metastasis rates of deep cervical lymph nodes were 100% in all three groups on CT-LG. The CT attenuation value of CT-LG reached peak values of 400 and 600 Hu at 1 and 3 min after the injection, which then decreased gradually. In this study, CT-LG could demonstrate the internal architecture of lymph nodes and their lymphatic vessels, and therefore may have the advantages of radiological methods such as B ultrasound, CT, magnetic resonance imaging and positron emission tomography. PMID:25789046

  7. Radio-frequency ablation-based studies on VX2rabbit models for HCC treatment.

    PubMed

    Bimonte, Sabrina; Leongito, Maddalena; Piccirillo, Mauro; de Angelis, Cristina; Pivonello, Claudia; Granata, Vincenza; Izzo, Francesco

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide with high morbidity, mortality and increasing incidence. It is of note that the main curative therapies for HCC are hepatic resection and transplantation although the majority of patients at the time of presentation are not eligible for resection or orthotopic liver transplantation (OLT) due to the underlying cirrhosis. Currently, a variety of loco-regional therapies, including radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), microwave coagulation therapy (MCT), transarterial chemoembolization (TACE) and others, have been developed as alternative treatment options for HCC. Among these techniques, RFA is currently the most widely used treatment, due to its several advantages, such as safety and efficacy. To date, the effectiveness of RFA for HCC is reduced by the presence of residual tumor as a consequence of insufficient treatment. In order to ameliorate the effects of RFA on HCC, several in vivo studies, have been performed on its application as single or in combination treatment with drugs or others loco-regional therapies, by using rabbit VX2 liver model. This represents an ideal model of liver cancers and is widely used for imaging and other experimental studies due to the rapid growth of these tumors and their similarity to human hepatocellular carcinoma. In order to elucidate the therapeutic potential of RFA with adjuvant treatments for HCC, we reviewed the latest findings on the RFA-based studies in rabbit VX2 hepatocarcinoma models. PMID:27525037

  8. Transarterial oily chemoembolization with lidamycin shows potent therapeutic efficacy in VX2 rabbit liver tumor

    PubMed Central

    Zhong, Genshen; Qi, Jinsong; Huo, Shuhua; Xue, Huichao; Xu, Zhishan; Li, Jinsong; Zhou, Yanjun; Wu, Minna; Li, Liang

    2015-01-01

    Transarterial oily chemoembolization (TOCE) is one of the most effective approaches for the treatment of patients with hepatocellular carcinoma (HCC), who are not suitable for surgical therapy. Lidamycin (LDM), a potent antitumor antibiotic, demonstrates good antitumor efficacy in various tumor types, both in vitro and in vivo. In this study, the antitumor efficacy of LDM combined with TOCE against the rabbit VX2 tumor was assessed. A toxicity assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) demonstrated that a combination of LDM with lipiodol did not impair the cytotoxicity of LDM against HepG2 cells in vitro. Using TOCE in rabbit VX2 tumor models, LDM showed a more powerful inhibitory effect against the tumor and lowered the expression levels of proliferating cell nuclear antigen (PCNA), cluster of differentiation 31 (CD31), and vascular endothelial growth factor (VEGF) compared to Adriamycin (ADM); moreover, this improvement was not accompanied by an increase of hepatotoxicity as shown by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. These results suggested that LDM combined with TOCE may be a feasible strategy in HCC therapy in the future. PMID:26543376

  9. Inflammation and cancer: inhibiting the progression of residual hepatic VX2 carcinoma by anti-inflammatory drug after incomplete radiofrequency ablation

    PubMed Central

    Jiang, Tao; Zhang, Xianjie; Ding, Jing; Duan, Bingwei; Lu, Shichun

    2015-01-01

    Background: Accelerated progression of residual hepatocellular carcinoma (HCC) after incomplete radiofrequency ablation (RFA) has been reported more frequently. Recent data have redefined the concept of inflammation as a critical component of tumor progression. However, there has been little understanding regarding the relationship between progression of residual HCC and the inflammation induced by thermal destruction of the tumor after RFA. The present study was designed to determine whether inflammation facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms. Methods: Forty-eight rabbits were each implanted with two VX2 hepatic tumors via supraumbilical median laparotomy. One of the tumors in two different lobes was ablated by RFA. All the rabbits were then randomly divided into four groups (12 rabbits in each group) receiving anti-inflammatory treatment with different doses of aspirin: control group, AS-L group (aspirin, 5 mg/kg/d), AS-M group (aspirin, 20 mg/kg/d), and AS-H group (aspirin, 100 mg/kg/d). The levels of serum interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) were detected to evaluate the effect of the anti-inflammation. Tumor growth, lung and kidney metastasis, and survival were assessed. The expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and cysteinyl aspartate specific proteinase 3 (caspase-3) in residual tumor was examined by immunohistochemistry and Western-blotting. Results: The levels of serum IL-6, hs-CRP, and TNF-α in the AS-H group decreased significantly in comparison with those of the control group (P<0.05). The focal tumor volume and lung and kidney metastases of rabbits in the AS-H group were less significant compared with those of the control group (P<0.05). The expression of PCNA, MMP-9, and VEGF in the AS-H group decreased

  10. Relevance of Rabbit VX2 Tumor Model for Studies on Human Hepatocellular Carcinoma: A MicroRNA-Based Study

    PubMed Central

    Aravalli, Rajagopal N.; Cressman, Erik N. K.

    2015-01-01

    MicroRNAs are small (~22 nt), noncoding RNA molecules that have critical cellular functions in proliferation, differentiation, angiogenesis and apoptosis. miRNA expression profiling has been used to create signatures of solid tumors and, in many cases, it has been shown to correlate with the severity of the disease. The rabbit VX2 tumor model has been used widely to study a number of human cancers. Our objective in this study is to generate an miRNA signature of the VX2 tumor and to identify miRNAs that are highly expressed in this aggressive tumor. In this study, we performed miRNA profiling of the rabbit VX2 tumor using a microarray that has probes for 1292 unique miRNAs. Their expression in tumor samples was quantified and analyzed. We found that 35 miRNAs were significantly up-regulated in the VX2 tumor. Among these, 13 human miRNAs and eight members of the let-7 family were previously identified in cancers. In addition, we show that the expression of three miRNAs (miR-923, miR-1275, and miR-1308) is novel for the rabbit VX2 tumor, and their expression was not previously shown to be associated with any type of cancer. For the first time, we show the miRNA signature profile for a solid tumor in a rabbit model. miRNAs highly expressed in the VX2 tumor may serve as novel candidates for molecular biomarkers and as potential drug targets. PMID:26690234

  11. Low contrast medium and radiation dose for hepatic computed tomography perfusion of rabbit VX2 tumor

    PubMed Central

    Zhang, Cai-Yuan; Cui, Yan-Fen; Guo, Chen; Cai, Jing; Weng, Ya-Fang; Wang, Li-Jun; Wang, Deng-Bin

    2015-01-01

    AIM: To evaluate the feasibility of low contrast medium and radiation dose for hepatic computed tomography (CT) perfusion of rabbit VX2 tumor. METHODS: Eleven rabbits with hepatic VX2 tumor underwent perfusion CT scanning with a 24-h interval between a conventional tube potential (120 kVp) protocol with 350 mgI/mL contrast medium and filtered back projection, and a low tube potential (80 kVp) protocol with 270 mgI/mL contrast medium with iterative reconstruction. Correlation and agreement among perfusion parameters acquired by the conventional and low dose protocols were assessed for the viable tumor component as well as whole tumor. Image noise and tumor-to-liver contrast to noise ratio during arterial and portal venous phases were evaluated. RESULTS: A 38% reduction in contrast medium dose (360.1 ± 13.3 mgI/kg vs 583.5 ± 21.5 mgI/kg, P < 0.001) and a 73% decrease in radiation dose (1898.5 mGy • cm vs 6951.8 mGy • cm) were observed. Interestingly, there was a strong positive correlation in hepatic arterial perfusion (r = 0.907, P < 0.001; r = 0.879, P < 0.001), hepatic portal perfusion (r = 0.819, P = 0.002; r = 0.831, P = 0.002), and hepatic blood flow (r = 0.945, P < 0.001; r = 0.930, P < 0.001) as well as a moderate correlation in hepatic perfusion index (r = 0.736, P = 0.01; r = 0.636, P = 0.035) between the low dose protocol with iterative reconstruction and the conventional protocol for the viable tumor component and the whole tumor. These two imaging protocols provided a moderate but acceptable agreement for perfusion parameters and similar tumor-to-liver CNR during arterial and portal venous phases (5.63 ± 2.38 vs 6.16 ± 2.60, P = 0.814; 4.60 ± 1.27 vs 5.11 ± 1.74, P = 0.587). CONCLUSION: Compared with the conventional protocol, low contrast medium and radiation dose with iterative reconstruction has no significant influence on hepatic perfusion parameters for rabbits VX2 tumor. PMID:25954099

  12. An implantable and controlled drug-release silk fibroin nanofibrous matrix to advance the treatment of solid tumour cancers.

    PubMed

    Xie, Maobin; Fan, Dejun; Chen, Yufeng; Zhao, Zheng; He, Xiaowen; Li, Gang; Chen, Aizheng; Wu, Xiaojian; Li, Jiashen; Li, Zhi; Hunt, John A; Li, Yi; Lan, Ping

    2016-10-01

    The development of more effective cancer therapeutic strategies are still critically required. The maximization of the therapeutic effect in combination with avoiding the severe side effects on normal tissues when using chemotherapy drugs is still an urgent problem that requires improvements urgently. Here we provide implantable and controllable drug-release that utilises silk fibroin (SF) as a nanofibrous drug delivery system (DDS) for cancer treatment. A nanofibrous structure with controllable fibre diameter (<100 nm) was produced. The drug release rate of the SF DDS was controlled by applying a post-treatment process. In vitro anti-cancer (HCT116) results indicated that curcumin (CM)-SF nanofibrous matrix had a superior anti-cancer potential when the concentration was >5 μg/mL. The mechanism could be explained by the cell cycle being held in the S phase. The toxic effect on normal cells (NCM460) was minimized by using a treatment concentration range (5-20 μg/mL). Implantation of this DDS into the tumour site inhibited the growth of solid tumour; this offers an alternative approach for novel cancer therapy. PMID:27376557

  13. Combination Therapy of Transcatheter Arterial Chemoembolization and Arterial Administration of Antiangiogenesis on VX2 Liver Tumor

    SciTech Connect

    Deng Gang; Zhao DenglLing; Li Guangchao; Yu Hui; Teng Gaojun

    2011-08-15

    Purpose: This study was designed to evaluate the antitumorigenic efficiency of Endostar (an antiangiogenic agent) arterially administrated combined with transcatheter arterial chemoembolization (TACE) on liver tumor, and validation of perfusion CT for quantitative measurements of the results.Experimental DesignThirty rabbits bearing VX2 liver tumors were randomly and equally distributed into three groups. One of the following treatment protocols was performed in each group: 1) group 1 was treated with TACE and simultaneously arterially administrated Endostar; 2) group 2 with TACE alone, and 3) a control group that had saline injected through hepatic artery. Routine CT scan was performed before treatment, and perfusion CT imaging was performed 2 weeks after treatment. Immunohistochemical biomarkers of microvascular density (MVD) and the expression of vascular endothelial growth factor (VEGF) were measured for assessments of angiogenesis. Results: We observed a statistically significant reduction from the control in the volume, growth rate, and size of the tumor 2 weeks after treatment with both TACE plus Endostar and with TACE alone (P < 0.01). Although there was no statistically significant difference in tumor size between the group with TACE plus Endostar and the group with TACE alone (P > 0.05), MVD and VEGF were significantly less expressed in the TACE plus Endostar group than both groups with TACE alone and the control group (P < 0.01). Blood flow (BF), blood volume (BV), and permeability-surface area products (PS) in the group with TACE plus Endostar on perfusion CT were significantly higher than other two groups (P < 0.05), which were positively correlated with the MVD and VEGF values (P < 0.05). Conclusions: TACE with arterial administration of Endostar simultaneously significantly inhibited the angiogenesis biomarkers associated with TACE in a rabbit model bearing VX2 liver tumor, which indicates that the combined treatment protocol may have potential

  14. Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants - a bio-mathematical model

    NASA Astrophysics Data System (ADS)

    Yue, Ning; Chen, Zhe; Nath, Ravinder

    2002-04-01

    Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both 125I and 103Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T) = Vp (1 + M exp(-0.693T/Te)) where Vp is the prostate volume before implantation, M is the edema magnitude and Te is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. Λg(r) αBED), where α is the linear coefficient of the survival curve. The tumour cell survival was calculated for both 125I and 103Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days and a magnitude of 50%, the edema increased tumour cell survival by about 1 and 2 orders of magnitude for 125I and 103Pd seed implants respectively. At the extreme (95% edema magnitude and an edema half-life of 30 days), the increase was more than 3 and 5 orders of magnitude for 125I and 103Pd seed implants respectively. The absolute increases were almost independent of TPDT and the prostate edema did not significantly change the effective treatment time. Tumour cell survival for prostate undergoing CLDRI using 125I or 103Pd seeds may be increased substantially due to the presence of edema caused by surgical trauma. This effect appears to be more pronounced for

  15. A small interfering RNA targeting vascular endothelial growth factor efficiently inhibits growth of VX2 cells and VX2 tumor model of hepatocellular carcinoma in rabbit by transarterial embolization-mediated siRNA delivery

    PubMed Central

    Zou, Yu; Guo, Chuan-Gen; Yang, Zheng-Gang; Sun, Jun-Hui; Zhang, Min-Ming; Fu, Cai-Yun

    2016-01-01

    Introduction Hepatocellular carcinoma is currently the second leading cause of cancer-related deaths worldwide with an increasing incidence. Objective The objective of this study is to investigate the effect of vascular endothelial growth factor small interfering RNA (VEGF-siRNA) on rabbit VX2 carcinoma cell viability in vitro and the effect of transarterial embolization (TAE)-mediated VEGF-siRNA delivery on the growth of rabbit VX2 liver-transplanted model in vivo. Methods Quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot technologies were used to detect the expression level of VEGF. TAE and computed tomography scan were used to deliver the VEGF-siRNA and detect the tumor volume in vivo, respectively. Microvessel density was detected by immunohistochemistry with CD34 antibody. A biochemical autoanalyzer was used to evaluate the hepatic and renal toxicity. Results The designed VEGF-siRNAs could effectively decrease the expression levels of VEGF mRNA and protein in vitro and in vivo. In vitro, the viability of rabbit VX2 carcinoma cells was reduced by 38.5%±7.3% (VEGF-siRNA no 1) and 30.0%±5.8% (VEGF-siRNA no 3) at 48 hours after transfection. Moreover, in rabbit VX2 liver-transplanted model, the growth ratios of tumors at 28 days after TAE-mediated siRNA delivery were 155.18%±19.42% in the control group, 79.67%±19.63% in the low-dose group, and 36.09%±15.73% in the high-dose group, with significant differences among these three groups. Microvessel density dropped to 34.22±4.01 and 22.63±4.07 in the low-dose group and high-dose group, respectively, compared with the control group (57.88±5.67), with significant differences among these three groups. Furthermore, inoculation of VX2 tumor into the liver itself at later stage induced significant increase in alanine aminotransferase and aspartate aminotransferase, indicating an obvious damage of liver functions, while treatment of VX2 tumor via TAE

  16. Antitumoral Effect of Sunitinib-eluting Beads in the Rabbit VX2 Tumor Model.

    PubMed

    Bize, Pierre; Duran, Rafael; Fuchs, Katrin; Dormond, Olivier; Namur, Julien; Decosterd, Laurent A; Jordan, Olivier; Doelker, Eric; Denys, Alban

    2016-08-01

    Purpose To measure plasmatic sunitinib concentration (PSC) and intratumoral sunitinib concentration (ITSC) after transcatheter arterial chemoembolization (TACE) with two different sizes of sunitinib-eluting beads (SEBs) in rabbits with VX2 hepatic allografts and to investigate treatment effects on vascular endothelial growth factor receptor type 2 (VEGFR2) phosphorylation, tumor volume, and histopathologic changes. Materials and Methods The protocol was approved by the French Ethics Committee for Animal Experiments (Comité d'Ethique en Expérimentation Animale du Centre INRA de Jouy-en-Josas et AgroParisTech, or COMETHEA, approval no. 11/028). Two experiments were performed. In the first, seven animals received 0.05 mL of 100-300-μm SEBs (1.5 mg of sunitinib) in the hepatic artery, and six animals received saline injections. In the second, eight animals received 0.05 mL of 70-150-μm SEBs (1.5 mg of sunitinib), seven received 0.05 mL of 70-150-μm unloaded beads, and seven received oral sunitinib (6 mg every day). Tumor size was monitored with ultrasonography. PSC, ITSC, and phosphorylation of VEGFR2 were assessed on days 1 and 14. After the animals were sacrificed, histopathologic analysis was performed. The Kruskal-Wallis test, Mann-Whitney U test, and Fisher exact test were used to look for statistically significant differences between groups. Results Maximum PSC after TACE with 100-300-μm SEBs was 0.002 μg/mL on day 1. ITSC was 17.8 μg/g on day 1 and 0.16 μg/g on day 14. After TACE with 70-150-μm SEBs, ITSC was 40.4 μg/g on day 1 and 27.4 μg/g on day 14. Phosphorylation of VEGFR2 was inhibited until day 14 after TACE with both sizes of SEBs. The size of VX2 tumors treated with 70-150-μm SEB TACE increased less (-2%) than that of tumors treated with unloaded beads (+42%) and oral sunitinib (6 mg every day; +1853%; P = .044). Conclusion SEB TACE resulted in minimal PSC, high ITSC, and sustained VEGFR2 phosphorylation inhibition until day 14. (©) RSNA

  17. Quantum Phase Transitions and Multicriticality in Ta(Fe1-xVx)2

    NASA Astrophysics Data System (ADS)

    Brando, Manuel; Kerkau, Alexander; Todorova, Adriana; Yamada, Yoshihiro; Khuntia, Panchanan; Förster, Tobias; Burkhard, Ulrich; Baenitz, Michael; Kreiner, Guido

    2016-08-01

    We present a comprehensive study of synthesis, structure analysis, transport and thermodynamic properties of the C14 Laves phase Ta(Fe1-xVx)2. Our measurements confirm the appearance of spin-density wave (SDW) order within a dome-like region of the x-T phase diagram with vanadium content 0.02 < x < 0.3. Our results indicate that on approaching TaFe2 from the vanadium-rich side, ferromagnetic (FM) correlations increase faster than the antiferromagnetic (AFM) ones. This results in an exchange-enhanced susceptibility and in the suppression of the SDW transition temperature for x < 0.13 forming the dome-like shape of the phase diagram. This effect is strictly related to a significant lattice distortion of the crystal structure manifested in the c/a ratio. At x = 0.02 both FM and AFM energy scales have similar strength and the system remains paramagnetic down to 2 K with an extremely large Stoner enhancement factor of about 400. Here, spin fluctuations dominate the temperature dependence of the resistivity ρ ∝ T3/2 and of the specific heat C/T ∝ -log(T) which deviate from their conventional Fermi liquid forms, inferring the presence of a quantum critical point of dual nature.

  18. Efficacy of MR-guided Focused Ultrasound Thermal Ablation of Rabbit VX2 Tumors

    NASA Astrophysics Data System (ADS)

    Yin, Xiangtao; Zhang, Yongzhi; Tam, Karen; McDannold, Nathan; Hynynen, Kullervo

    2006-05-01

    This animal study addresses the treatment efficacy of the MR-guided thermal ablation technique and temperature monitoring in rabbit tumors. Specifically, the relationship between the thermal dose coverage in the tumors and the rabbit survival rate was investigated. Two groups of rabbits (14 in back tumor group and 12 in thigh tumor group) were treated with the ExAblate-2000 MR-guided focused ultrasound thermal ablation system one week after being injected VX2 tumor cells into their back muscle or thigh muscle. Sonication was repeated twice in a planned location in the tumor region and monitored in the coronal and sagittal planes respectively to ensure volumetric thermal dose monitoring. MR T1 Gad-enhanced contrast images of the tumors were obtained immediately after treatment and post-treatment at 2, 4, 8 and 12 weeks (or before sacrificing the rabbits). In the thigh tumor rabbits group, tumor recurrence was observed for only one and the other eleven rabbits survived without tumor recurrence at 4 weeks. Aiming at a longer survival time, the rabbits with back tumors had up to 12 weeks survival time. Three rabbits survived to 12 weeks without tumor recurrence in the back tumor group, yielding less promising survival rate than that of the thigh tumor group survival test. Successful thermal ablation (i.e. lack of recurrence) was demonstrated when the tumors received full thermal dose coverage.

  19. Visualisation of liver tumours using hand-held real-time strain imaging: results of animal experiments

    PubMed Central

    Melodelima, D; Chenot, J; Souchon, R; Rivoire, M; Chapelon, J-Y

    2012-01-01

    Objective Surgical resection is the only curative option for colorectal hepatic metastases. Intra-operative localisation of these metastases during hepatic resection is performed by intra-operative B-mode imaging and palpation. Because liver metastases are stiffer than normal tissues, elastography may be a useful complement to B-mode imaging. This paper reports quantitative measures of the image quality attained during intra-operative real-time elastographic visualisation of liver metastasis. Methods VX2 tumours were implanted in the liver of eight rabbits and were scanned in vivo. Measurements of the tumour dimensions obtained via elastography were compared with those obtained using B-mode imaging and with gross pathology. Results Measurements of tumour diameters were similar when obtained by intra-operative elastography and pathological measurement methods (mean difference±standard deviation, 0.1±0.9 mm). The contrast between tumours and normal tissues was significantly higher (p<0.05) in elastograms (26±10 dB contrast) than in sonograms (1±1 dB contrast). Sensitivity and specificity for detecting tumours using intra-operative elastography were 100% and 88%, respectively, and positive and negative predictive values were 89% and 100%, respectively. In two cases elastograms were able to detect a tumour that was ambiguous in B-mode images. Conclusion Combined hand-held B-mode/strain imaging may provide additional information that is relevant for detection of liver metastases that may be missed by standard B-mode imaging alone, such as small and/or isoechoic tumours. PMID:22253340

  20. Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model

    SciTech Connect

    Rao, Pramod P.; Pascale, Florentina; Seck, Atman; Auperin, Anne; Drouard-Troalen, Laurence; Deschamps, Frederic; Teriitheau, Christophe; Paci, Angelo; Denys, Alban; Bize, Pierre; Baere, Thierry de

    2012-12-15

    Purpose: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. Material and Methods: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.ResultsTwelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). Conclusion: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

  1. Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

    SciTech Connect

    Cao Wei; Li Jing; Wu Zhiqun; Zhou Changxi; Liu Xi; Wan Yi; Duan Yunyou

    2013-06-15

    Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 Degree-Sign C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 Degree-Sign C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

  2. Enhanced Ablation of High Intensity Focused Ultrasound with Microbubbles: An Experimental Study on Rabbit Hepatic VX2 Tumors

    SciTech Connect

    He Wei; Wang Wei Zhou Ping; Wang, Yixiang J.; Zhou Peng; Li Ruizhen; Wang Jinsheng; Ahuja, Anil T.

    2011-10-15

    Purpose: This study was designed to assess the enhanced effect of high intensity focused ultrasound (HIFU) ablation with microbubbles on rabbit hepatic VX2 tumors and to compare the detection sensitivity of CEUS and CECT to determine the residual viable tissue after ablation of HIFU. Methods: Forty rabbits with hepatic VX2 tumors were randomly separated into two groups (20 animals per group) before HIFU ablation. A bolus of 0.2 mL of saline or a microbubble-based ultrasound (US) contrast agent was injected intravenously to group I rabbits and group II rabbits, respectively. The HIFU ablation procedure was started 15 s after the injection. Tumors were examined with grayscale contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) immediately before and after HIFU ablation. Histopathologic assessment was performed immediately after treatment imaging. Results: Before ablation, intense contrast enhancement during arterial phase was observed at the whole tumors or the periphery of the tumors by CEUS and CECT. Lower HIFU energy was used in group II than in group I (P < 0.001). Histopathologic assessment revealed local residual viable tumor tissues due to incomplete ablation in 47.4% (9/19) of tumors in group I and 10% (2/20) of tumors in group II (P < 0.05). The concordance rate of CEUS (90.9%) with histopathology on residual tumor detection was higher than that of CECT (27.3%, P < 0.05). Conclusions: Introduction of the microbubble agent enhances HIFU therapeutic efficacy. CEUS proves to have high sensitivity in assessment of residual viable rabbit VX2 tumor after HIFU.

  3. Correlation of Doxorubicin Delivery and Tumor Necrosis after Drug-eluting Bead Transarterial Chemoembolization of Rabbit VX2 Liver Tumors.

    PubMed

    Gaba, Ron C; Emmadi, Rajyasree; Parvinian, Ahmad; Casadaban, Leigh C

    2016-09-01

    Purpose To quantify the correlation between doxorubicin (DOX) delivery and tumor necrosis after drug-eluting bead (DEB) transarterial chemoembolization (TACE). Materials and Methods In this animal care committee-approved study, New Zealand white rabbit VX2 liver tumors were treated transarterially with DOX-loaded 70-150-μm DEBs in five treatment groups with varying drug doses: sham (saline), 0 mg, 12.5 mg, 25 mg, and 37.5 mg. DEB TACE was followed by 3- and 7-day sacrifice, tumor harvest, and sectioning. Drug delivery was assessed by using fluorescence imaging, and tumor necrosis was quantified by means of histologic analysis. Statistical correlation of DOX delivery and tumor necrosis was performed by using the Spearman rank correlation coefficient (ρ). Results Thirty-six VX2 tumors (median diameter, 1.3 cm) in 20 rabbits (median weight, 2.8 kg) underwent successful DEB TACE. Treatment groups included eight, seven, eight, five, and eight tumors of similar size (P > .05). Tumors showed progressively greater DOX extent (sham, 0%; 0 mg, 0%; 12.5 mg, 3%; 25 mg, 20%; and 37.5 mg, 27%) and intensity (sham, 0.4; 0 mg, 1.9; 12.5 mg, 8.5; 25 mg, 9.6; and 37.5 mg, 18.3) and higher median percentage necrosis (sham, 68%; 0 mg, 64%; 12.5 mg, 76%; 25 mg, 78%; and 37.5 mg, 83%) across DOX treatment groups. Correlation of DOX extent (ρ = 0.975, P = .005) and intensity (ρ = 0.900, P = .037) with percentage tumor necrosis was statistically significant. Conclusion Incremental increases in DOX correlate with greater necrosis in rabbit VX2 liver tumors after DEB TACE. This result indicates an essential role for chemotherapy-induced cytotoxicity in TACE effectiveness and supports the use of chemotherapeutic drugs in transarterial therapy. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:26967144

  4. Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

    SciTech Connect

    Kageyama, Ken Yamamoto, Akira Okuma, Tomohisa Hamamoto, Shinichi Takeshita, Toru Sakai, Yukimasa Nishida, Norifumi Matsuoka, Toshiyuki Miki, Yukio

    2013-10-15

    Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

  5. Ultrasonograpy of VX-2 Liver Tumor in Rabbit Treated by High Intensity Focused Ultrasound Combined with Microbubble Contrast Agent

    NASA Astrophysics Data System (ADS)

    Xiaojuan, Ji; Jinqing, Li; Zhibiao, Wang; Jianzhong, Zou; Wenzhi, Chen; Jin, Bai

    2007-05-01

    Objective: To assess the value of sonographic appearance and to investigate the sonographic character of VX-2 liver tumor in rabbit treated by high intensity focused ultrasound (HIFU) combined with microbubble contrast agent. Methods: Forty-five rabbits bearing VX-2 tumors were randomly averagely assigned into three groups. In group A irradiation was sustained until the target region became hyperechoic. In group B therapy was stopped as soon as hyperecho occurred, and in group C irradiation time was prolonged to ensure the occurrence of coagulation necrosis. Results: Exposure duration for tumors treated purely with HIFU was the longest, whilst the use of microbubble contrast agent combined with HIFU shortened the exposure duration significantly. The gross examination and ultrasonogram coagulation necrosis area measurements correlated strongly (r=0.986,P<0.05) in the microbubble-enhanced HIFU group. Conclusion: It was feasible to enhance HIFU therapy with microbubble contrast agent. The characteristic change in the ultrasound images made it possible to assess the enhanced HIFU therapeutic efficacy in order to adjust the treatment program.

  6. Poly(lactide-co-glycolide) Microspheres for MRI-Monitored Delivery of Sorafenib in a Rabbit VX2 model

    PubMed Central

    Chen, Jeane; White, Sarah B.; Harris, Kathleen R.; Li, Weiguo; Yap, Jonathan WT; Kim, Dong-Hyun; Lewandowski, Robert J.; Shea, Lonnie D.; Larson, Andrew C.

    2015-01-01

    Transcatheter arterial embolization and chemoembolization are standard locoregional therapies for hepatocellular carcinoma (HCC). However, these can result in tumor hypoxia, thus promoting tumor angiogenesis. The anti-angiogenic agent sorafenib is hypothesized to improve outcomes; however, oral administration limits patient tolerance. Therefore, the purpose of this study was to fabricate poly(lactide-co-glycolide) microspheres for local sorafenib delivery to tumors during liver-directed embolotherapies. Iron oxide nanoparticles (IONP) were co-encapsulated for magnetic resonance imaging (MRI) of microsphere delivery. Microspheres were fabricated using a double emulsion/solvent evaporation method and characterized for size, sorafenib and IONP content, and MRI properties. MRI was performed before and after intra-arterial microsphere infusions in a rabbit VX2 liver tumor model. The microspheres were 13 microns in diameter with 8.8% and 0.89% (w/w) sorafenib and IONP, respectively. 21% and 28% of the loaded sorafenib and IONP, respectively, released within 72 hours. Rabbit VX2 studies demonstrated that sorafenib microspheres normalized VEGFR 2 activity and decreased microvessel density. Quantitative MRI enabled in vivo visualization of intra-hepatic microsphere distributions. These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors. PMID:26022791

  7. Poly(lactide-co-glycolide) microspheres for MRI-monitored delivery of sorafenib in a rabbit VX2 model.

    PubMed

    Chen, Jeane; White, Sarah B; Harris, Kathleen R; Li, Weiguo; Yap, Jonathan W T; Kim, Dong-Hyun; Lewandowski, Robert J; Shea, Lonnie D; Larson, Andrew C

    2015-08-01

    Transcatheter arterial embolization and chemoembolization are standard locoregional therapies for hepatocellular carcinoma (HCC). However, these can result in tumor hypoxia, thus promoting tumor angiogenesis. The anti-angiogenic agent sorafenib is hypothesized to improve outcomes; however, oral administration limits patient tolerance. Therefore, the purpose of this study was to fabricate poly(lactide-co-glycolide) microspheres for local sorafenib delivery to tumors during liver-directed embolotherapies. Iron oxide nanoparticles (IONP) were co-encapsulated for magnetic resonance imaging (MRI) of microsphere delivery. Microspheres were fabricated using a double emulsion/solvent evaporation method and characterized for size, sorafenib and IONP content, and MRI properties. MRI was performed before and after intra-arterial microsphere infusions in a rabbit VX2 liver tumor model. The microspheres were 13 microns in diameter with 8.8% and 0.89% (w/w) sorafenib and IONP, respectively. 21% and 28% of the loaded sorafenib and IONP, respectively, released within 72 h. Rabbit VX2 studies demonstrated that sorafenib microspheres normalized VEGFR 2 activity and decreased microvessel density. Quantitative MRI enabled in vivo visualization of intra-hepatic microsphere distributions. These methods should avoid systemic toxicities, with MRI permitting follow-up confirmation of microsphere delivery to the targeted liver tumors. PMID:26022791

  8. Successful treatment of bleeding large duodenal gastrointestinal stromal tumour in a patient under dual antiplatelet therapy after recent drug-eluting coronary stent implantation

    PubMed Central

    Fukuyama, Keita; Fujikawa, Takahisa; Kuramitsu, Shoichi; Tanaka, Akira

    2014-01-01

    We report a case of a 69-year-old man who started dual antiplatelet therapy (APT) with aspirin and clopidogrel after recent implantation of drug-eluting coronary stent and developed massive bleeding due to large duodenal gastrointestinal stromal tumour (GIST). Following endoscopic haemostasis and discontinuation of dual APT, neoadjuvant chemotherapy with imatinib was started under continuation of ‘single’ APT with aspirin. A good chemotherapeutic response was achieved without recurrence of bleeding, and subsequent less invasive surgical resection of the tumour was performed, while preoperative single APT was continued for prevention of stent thrombosis. The patient recovered well without any thromboembolic or bleeding events. Neoadjuvant imatinib therapy and subsequent less invasive surgery under continuation of APT is one of the preferred approaches for patients with duodenal GIST with severe thromboembolic comorbidities, as in the current case. PMID:24777088

  9. Multimodality Imaging of Ethiodized Oil-loaded Radiopaque Microspheres during Transarterial Embolization of Rabbits with VX2 Liver Tumors.

    PubMed

    Tacher, Vania; Duran, Rafael; Lin, MingDe; Sohn, Jae Ho; Sharma, Karun V; Wang, Zhijun; Chapiro, Julius; Gacchina Johnson, Carmen; Bhagat, Nikhil; Dreher, Matthew R; Schäfer, Dirk; Woods, David L; Lewis, Andrew L; Tang, Yiqing; Grass, Michael; Wood, Bradford J; Geschwind, Jean-François

    2016-06-01

    Purpose To assess the visibility of radiopaque microspheres during transarterial embolization (TAE) in the VX2 rabbit liver tumor model by using multimodality imaging, including single-snapshot radiography, cone-beam computed tomography (CT), multidetector CT, and micro-CT. Materials and Methods The study was approved by the institutional animal care and use committee. Fifteen VX2-tumor-bearing rabbits were assigned to three groups depending on the type of embolic agent injected: 70-150-μm radiopaque microspheres in saline (radiopaque microsphere group), 70-150-μm radiopaque microspheres in contrast material (radiopaque microsphere plus contrast material group), and 70-150-μm radiolucent microspheres in contrast material (nonradiopaque microsphere plus contrast material group). Rabbits were imaged with single-snapshot radiography, cone-beam CT, and multidetector CT. Three to 5 weeks after sacrifice, excised livers were imaged with micro-CT and histologic analysis was performed. The visibility of the embolic agent was assessed with all modalities before and after embolization by using a qualitative three-point scale score reading study and a quantitative assessment of the signal-to-noise ratio (SNR) change in various regions of interest, including the tumor and its feeding arteries. The Kruskal-Wallis test was used to compare the rabbit characteristics across groups, and the Wilcoxon signed rank test was used to compare SNR measurements before and after embolization. Results Radiopaque microspheres were qualitatively visualized within tumor feeding arteries and targeted tissue with all imaging modalities (P < .05), and their presence was confirmed with histologic examination. SNRs of radiopaque microsphere deposition increased after TAE on multidetector CT, cone-beam CT, and micro-CT images (P < .05). Similar results were obtained when contrast material was added to radiopaque microspheres, except for additional image attenuation due to tumor enhancement. For the

  10. Quantum size effects in layered VX2 (X = S, Se) materials: Manifestation of metal to semimetal or semiconductor transition

    NASA Astrophysics Data System (ADS)

    Wasey, A. H. M. Abdul; Chakrabarty, Soubhik; Das, G. P.

    2015-02-01

    Most of the two dimensional (2D) transition metal dichalcogenides (TMDC) are nonmagnetic in pristine form. However, 2D pristine VX2 (X = S, Se, Te) materials are found to be ferromagnetic. Using spin polarized density functional theory (DFT) calculations, we have studied the electronic, magnetic, and surface properties of this class of materials in both trigonal prismatic H- and octahedral T-phase. Our calculations reveal that they exhibit materially different properties in those two polymorphs. Most importantly, detailed investigation of electronic structure explored the quantum size effect in H-phase of these materials thereby leading to metal to semimetal (H-VS2) or semiconductor (H-VSe2) transition when downsizing from bilayer to corresponding monolayer.

  11. Newtype single-layer magnetic semiconductor in transition-metal dichalcogenides VX2 (X = S, Se and Te)

    PubMed Central

    Fuh, Huei-Ru; Chang, Ching-Ray; Wang, Yin-Kuo; Evans, Richard F. L.; Chantrell, Roy W.; Jeng, Horng-Tay

    2016-01-01

    We present a newtype 2-dimensional (2D) magnetic semiconductor based on transition-metal dichalcogenides VX2 (X = S, Se and Te) via first-principles calculations. The obtained indirect band gaps of monolayer VS2, VSe2, and VTe2 given from the generalized gradient approximation (GGA) are respectively 0.05, 0.22, and 0.20 eV, all with integer magnetic moments of 1.0 μB. The GGA plus on-site Coulomb interaction U (GGA + U) enhances the exchange splittings and raises the energy gap up to 0.38~0.65 eV. By adopting the GW approximation, we obtain converged G0W0 gaps of 1.3, 1.2, and 0.7 eV for VS2, VSe2, and VTe2 monolayers, respectively. They agree very well with our calculated HSE gaps of 1.1, 1.2, and 0.6 eV, respectively. The gap sizes as well as the metal-insulator transitions are tunable by applying the in-plane strain and/or changing the number of stacking layers. The Monte Carlo simulations illustrate very high Curie-temperatures of 292, 472, and 553 K for VS2, VSe2, and VTe2 monolayers, respectively. They are nearly or well beyond the room temperature. Combining the semiconducting energy gap, the 100% spin polarized valence and conduction bands, the room temperature TC, and the in-plane magnetic anisotropy together in a single layer VX2, this newtype 2D magnetic semiconductor shows great potential in future spintronics. PMID:27601195

  12. Pure Ethiodized Oil-based Transcatheter Ablative Therapy in Normal Rabbit Kidneys and Kidneys Inoculated with VX-2 Carcinoma

    SciTech Connect

    Konya, Andras; Stephens, L. Clifton; Wright, Kenneth C.

    2011-10-15

    Purpose: To evaluate the efficacy of ablation with selective arterial injection of pure ethiodized oil followed by arterial occlusion with 9:1 ethanol-Ethiodol mixture (EEM) and coil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma. Materials and Methods: All experiments were conducted with Animal Care and Use Committee approval. In six rabbits (group 1), one kidney was embolized with pure Ethiodol until capillary stasis, followed by injection of 9:1 EEM until arterial stasis and then coil placement into the main renal artery. In 12 other rabbits, one kidney was inoculated with VX-2 tumor. Ethiodol and EEM embolization and coil placement followed 7 days later (group 2, n = 6) or 11-14 days later (group 3, n = 6). Kidneys were evaluated (angiography, computed tomography, macro- and microscopy) 7 days after treatment. Results: Capillary stasis was achieved in groups 1, 2, and 3 with (mean {+-} standard deviation) 0.47 {+-} 0.03, 0.53 {+-} 0.02, and 0.56 {+-} 0.04 ml of pure Ethiodol, followed by 0.47 {+-} 0.05, 0.42 {+-} 0.03, and 0.38 {+-} 0.04 ml of EEM, respectively, which caused complete arterial occlusion in 17 of 18 kidneys. In group 1, all but one kidney showed at least 95% generalized coagulative necrosis. In group 2, all six kidneys exhibited 100% coagulative necrosis, with no viable tumor present. In group 3, 100% coagulative necrosis was present in all kidneys, with a small viable tumor in one. Conclusion: In the rabbit, selective arterial injection of pure Ethiodol can cause complete renal parenchyma and tumor ablation when it is followed by prompt, contiguous, and permanent occlusion of the arterial compartment.

  13. Newtype single-layer magnetic semiconductor in transition-metal dichalcogenides VX2 (X = S, Se and Te).

    PubMed

    Fuh, Huei-Ru; Chang, Ching-Ray; Wang, Yin-Kuo; Evans, Richard F L; Chantrell, Roy W; Jeng, Horng-Tay

    2016-01-01

    We present a newtype 2-dimensional (2D) magnetic semiconductor based on transition-metal dichalcogenides VX2 (X = S, Se and Te) via first-principles calculations. The obtained indirect band gaps of monolayer VS2, VSe2, and VTe2 given from the generalized gradient approximation (GGA) are respectively 0.05, 0.22, and 0.20 eV, all with integer magnetic moments of 1.0 μB. The GGA plus on-site Coulomb interaction U (GGA + U) enhances the exchange splittings and raises the energy gap up to 0.38~0.65 eV. By adopting the GW approximation, we obtain converged G0W0 gaps of 1.3, 1.2, and 0.7 eV for VS2, VSe2, and VTe2 monolayers, respectively. They agree very well with our calculated HSE gaps of 1.1, 1.2, and 0.6 eV, respectively. The gap sizes as well as the metal-insulator transitions are tunable by applying the in-plane strain and/or changing the number of stacking layers. The Monte Carlo simulations illustrate very high Curie-temperatures of 292, 472, and 553 K for VS2, VSe2, and VTe2 monolayers, respectively. They are nearly or well beyond the room temperature. Combining the semiconducting energy gap, the 100% spin polarized valence and conduction bands, the room temperature TC, and the in-plane magnetic anisotropy together in a single layer VX2, this newtype 2D magnetic semiconductor shows great potential in future spintronics. PMID:27601195

  14. Four-dimensional Transcatheter Intra-arterial Perfusion MR Imaging Before and After Uterine Artery Embolization in the Rabbit VX2 Tumor Model

    PubMed Central

    Chung, Johnathan C.; Wang, Dingxin; Lewandowski, Robert J.; Tang, Richard; Chrisman, Howard B.; Vogelzang, Robert L.; Woloschak, Gayle E.; Larson, Andrew C.; Omary, Reed A.; Ryu, Robert K.

    2010-01-01

    Purpose To test the hypothesis that four-dimensional (4D) transcatheter intra-arterial perfusion (TRIP) MR imaging can measure uterine fibroid perfusion changes immediately before and after uterine artery embolization (UAE) in the rabbit VX2 tumor model. Materials and Methods Eight VX2 uterine tumors were grown in 6 rabbits. After positioning a catheter within the uterine artery, we performed 4D TRIP-MRI measurements with 3 mL injections of 2.5% gadopentetate dimeglumine. We used a dynamic 3D spoiled-GRE sequence with in vivo B1-field correction for improved accuracy during perfusion quantification. We performed UAE using 1 mL of gelatin microspheres (2×106 particles; diameter 40-120 μm). Two regions-of-interest were drawn within each tumor upon perfusion maps. Functional embolic endpoints were reported as the mean percent reduction in fibroid tumor perfusion. Measurements before and after UAE were compared using paired t-tests (α = 0.05). Results VX2 uterine tumor perfusion decreased significantly from 27.1 at baseline to 7.09 after UAE (mL/min/100 mL tissue, p < 0.0001). Overall perfusion reduction was 76.3% (95% CI: 66.3%-86.3%). Conclusion 4D TRIP MRI can objectively quantify uterine fibroid perfusion reductions during UAE in VX2 rabbits. This technique could be used clinically to potentially determine an optimal embolic endpoint with the long-term goals of improving UAE success rates and minimizing procedure-related ischemic pain. PMID:20432349

  15. Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model

    PubMed Central

    Seidensticker, Max; Streit, Sebastian; Nass, Norbert; Wybranski, Christian; Jürgens, Julian; Brauner, Jan; Schulz, Nadine; Kalinski, Thomas; Seidensticker, Ricarda; Garlipp, Benjamin; Steffen, Ingo; Ricke, Jens; Dudeck, Oliver

    2016-01-01

    PURPOSE We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model. METHODS VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy. RESULTS The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE. CONCLUSION SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity. PMID:27328720

  16. Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique.

    PubMed

    Sun, Di; Wei, Cong; Shen, E; Ying, Tao; Hu, Bing

    2016-01-01

    Acoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 ± 0.19 m/s, 3.09 ± 0.40 m/s, 2.64 ± 0.37 m/s and 2.26 ± 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results. PMID:27381362

  17. Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique

    PubMed Central

    Sun, Di; Wei, Cong; Shen, E.; Ying, Tao; Hu, Bing

    2016-01-01

    Acoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 ± 0.19 m/s, 3.09 ± 0.40 m/s, 2.64 ± 0.37 m/s and 2.26 ± 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results. PMID:27381362

  18. Interferometric phase-contrast X-ray CT imaging of VX2 rabbit cancer at 35keV X-ray energy

    SciTech Connect

    Takeda, Tohoru; Wu Jin; Tsuchiya, Yoshinori; Lwin, Thet-Thet; Itai, Yuji; Yoneyama, Akio; Hyodo, Kazuyuki

    2004-05-12

    Imaging of large objects at 17.7-keV low x-ray energy causes huge x-ray exposure to the objects even using interferometric phase-contrast x-ray CT (PCCT). Thus, we tried to obtain PCCT images at high x-ray energy of 35keV and examined the image quality using a formalin-fixed VX2 rabbit cancer specimen with 15-mm in diameter. The PCCT system consisted of an asymmetrically cut silicon (220) crystal, a monolithic x-ray interferometer, a phase-shifter, an object cell and an x-ray CCD camera. The PCCT at 35 keV clearly visualized various inner structures of VX2 rabbit cancer such as necrosis, cancer, the surrounding tumor vessels, and normal liver tissue. Besides, image-contrast was not degraded significantly. These results suggest that the PCCT at 35 KeV is sufficient to clearly depict the histopathological morphology of VX2 rabbit cancer specimen.

  19. Imaging Intratumoral Nanoparticle Uptake After Combining Nanoembolization with Various Ablative Therapies in Hepatic VX2 Rabbit Tumors.

    PubMed

    Tam, Alda L; Melancon, Marites P; Abdelsalam, Mohamed; Figueira, Tomas Appleton; Dixon, Katherine; McWatters, Amanda; Zhou, Min; Huang, Qian; Mawlawi, Osama; Dunner, Kenneth; Li, Chun; Gupta, Sanjay

    2016-02-01

    Combining image-guided therapy techniques for the treatment of liver cancers is a strategy that is being used to improve local tumor control rates. Here, we evaluate the intratumoral uptake of nanoparticles used in combination with radiofrequency ablation (RFA), irreversible electroporation (IRE), or laser induced thermal therapy (LITT). Eight rabbits with VX2 tumor in the liver underwent one of four treatments: (i) nanoembolization (NE) with radiolabeled, hollow gold nanoparticles loaded with doxorubicin (⁶⁴Cu-PEG-HAuNS-DOX); (ii) NE + RFA; (iii) NE + IRE; (iv) NE +LITT. Positron emission tomography/computed tomography (PET/CT) imaging was obtained 1-hr or 18-hrs after intervention. Tissue samples were collected for autoradiography and transmission electron microscopy (TEM) analysis. PET/CT imaging at 1-hr showed focal deposition of oil and nanoparticles in the tumor only after NE+ RFA but at 18-hrs, all animals had focal accumulation of oil and nanoparticles in the tumor region. Autoradiograph analysis demonstrated nanoparticle deposition in the tumor and in the ablated tissues adjacent to the tumor when NE was combined with ablation. TEM results showed the intracellular uptake of nanoparticles in tumor only after NE + IRE. Nanoparticles demonstrated a structural change, suggesting direct interaction, potentially leading to drug release, only after NE + LITT. The findings demonstrate that a combined NE and ablation treatment technique for liver tumors is feasible, resulting in deposition of nanoparticles in and around the tumor. Depending on the ablative energy applied, different effects are seen on nanoparticle localization and structure. These effects should be considered when designing nanoparticles for use in combination with ablation technologies. PMID:27305763

  20. The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

    PubMed Central

    Dong, Shengli; Tang, Qibin; Long, Miaoyun; Guan, Jian; Ye, Lu; Li, Gaopeng

    2013-01-01

    Background/aim A local nanotherapy (LNT) combining the therapeutic efficacy of trans-arterial embolization, nanoparticles, and p53 gene therapy has been previously presented. The study presented here aimed to further improve the incomplete tumor eradication and limited survival enhancement and to elucidate the molecular mechanism of the LNT. Methods In a tumor-targeting manner, recombinant expressing plasmids harboring wild-type p53 and Rb were either co-transferred or transferred separately to rabbit hepatic VX2 tumors in a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex and Lipiodol® (Guerbet, Villepinte, France) emulsion via the hepatic artery. Subsequent co-expression of p53 and Rb proteins within the treated tumors was investigated by Western blotting and in situ analysis by laser-scanning confocal microscopy. The therapeutic effect was evaluated by the tumor growth velocity, apoptosis and necrosis rates, their sensitivity to Adriamycin® (ADM), mitomycin C, and fluorouracil, the microvessel density of tumor tissue, and the survival time of animals. Eventually, real-time polymerase chain reaction and enhanced chemiluminescence Western blotting were used to investigate the expressive changes of important genes related to the therapy. Results The administration procedure proved safe for the rabbits’ liver function, the p53 plus Rb LNT showed significantly better antitumoral effect and lower expression of malignant genes than the p53 or Rb LNT, although no significant difference was observed in animal survival when the p53 plus Rb LNT was compared with the p53 LNT. Conclusion Rb works synergistically with p53 in combined therapy mediated by a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex to augment the antitumoral effect through the downregulated expression of important genes related to apoptosis, necrosis, growth, differentiation and multidrug resistance of tumor cells. LNT with p53 and Rb is potentially an effective antitumor

  1. Transcatheter arterial embolization combined with radiofrequency ablation activates CD8+ T-cell infiltration surrounding residual tumors in the rabbit VX2 liver tumors

    PubMed Central

    Duan, Xu-Hua; Li, Teng-Fei; Zhou, Guo-Feng; Han, Xin-Wei; Zheng, Chuan-Sheng; Chen, Peng-fei; Feng, Gan-Sheng

    2016-01-01

    Purpose To evaluate the effect of transcatheter arterial embolization (TAE) combined with radiofrequency ablation (RFA) treatment (TAE + RFA) on the expression of heat shock protein 70 (HSP70) in residual tumors and explore the relationship between the HSP70 and CD8+ T-cell infiltrate surrounding residual tumors in the rabbit VX2 liver tumor model. Materials and methods Animals with VX2 liver tumors were randomized into four groups (control, TAE, RFA, and TAE + RFA) with 15 rabbits in each group. Five rabbits in each group were sacrificed on days 1, 3, and 7 after treatment. HSP70 expression and infiltration of CD8+ T-cells in the liver and residual tumors surrounding the necrosis zone were detected by immunohistochemistry staining. The maximal diameters of tumor necrosis, numbers of metastases, and tumor growth rate were compared on day 7 after treatment. Results TAE + RFA achieved larger maximal diameter of tumor necrosis, lower tumor growth rate, and fewer metastatic lesions, compared with other treatments on day 7. The number of CD8+ T-cells in the TAE + RFA group was significantly higher than in other groups on days 1, 3, and 7. There was a positive correlation between HSP70 expression level and infiltration of CD8+ T-cells surrounding the residual tumor on day 1 (r=0.9782, P=0.012), day 3 (r=0.93, P=0.021), and day 7 (r=0.8934, P=0.034). Conclusion In the rabbit VX2 liver tumor model, TAE + RFA activated the highest number of CD8+ T-cells surrounding residual tumors. TAE + RFA appears to be a beneficial therapeutic modality for tumor control and antitumor immune response in this model. PMID:27274279

  2. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan.

    PubMed

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-Ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal-regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  3. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

    PubMed Central

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  4. Prosthodontic rehabilitation of oral function in head-neck cancer patients with dental implants placed simultaneously during ablative tumour surgery: an assessment of treatment outcomes and quality of life.

    PubMed

    Schoen, P J; Raghoebar, G M; Bouma, J; Reintsema, H; Burlage, F R; Roodenburg, J L N; Vissink, A

    2008-01-01

    The aim of this prospective study was to assess treatment outcome and impact on quality of life of prosthodontic rehabilitation with implant-retained prostheses in head-neck cancer patients. Fifty patients were evaluated by standardized questionnaires and clinical assessment. All received the implants during ablative tumour surgery in native bone in the interforaminal area. About two-thirds of the patients (n=31) needed radiotherapy post-surgery. Both in irradiated and non-irradiated bone two implants were lost 18-24 months after installation. Peri-implant tissues had a healthy appearance. No cases of osteoradionecrosis occurred. In 15 patients no functional implant-retained lower dentures could be made for various reasons. The other 35 patients all functioned well, with an improvement in quality of life. Major improvement was observed in the non-irradiated patients. In the irradiated patients, less improvement in many functional items was observed, while items related to the oral sequelae of radiotherapy did not improve. Similar to the quality-of-life assessments, denture satisfaction was improved and tended to be higher in non-irradiated than irradiated patients. Implant-retained lower dentures can substantially improve the quality of life related to oral functioning and denture satisfaction in head-neck cancer patients. This effect is greater in non-irradiated than irradiated cancer patients. PMID:17766084

  5. Necrosis targeted radiotherapy with iodine-131-labeled hypericin to improve anticancer efficacy of vascular disrupting treatment in rabbit VX2 tumor models

    PubMed Central

    Shao, Haibo; Zhang, Jian; Sun, Ziping; Chen, Feng; Dai, Xu; Li, Yaming; Ni, Yicheng; Xu, Ke

    2015-01-01

    A viable rim of tumor cells surrounding central necrosis always exists and leads to tumor recurrence after vascular disrupting treatment (VDT). A novel necrosis targeted radiotherapy (NTRT) using iodine-131-labeled hypericin (131I-Hyp) was specifically designed to treat viable tumor rim and improve tumor control after VDT in rabbit models of multifocal VX2 tumors. NTRT was administered 24 hours after VDT. Tumor growth was significantly slowed down by NTRT with a smaller tumor volume and a prolonged tumor doubling time (14.4 vs. 5.7 days), as followed by in vivo magnetic resonance imaging over 12 days. The viable tumor rims were well inhibited in NTRT group compared with single VDT control group, as showed on tumor cross sections at day 12 (1 vs. 3.7 in area). High targetability of 131I-Hyp to tumor necrosis was demonstrated by in vivo SPECT as high uptake in tumor regions lasting over 9 days with 4.26 to 98 times higher radioactivity for necrosis versus the viable tumor and other organs by gamma counting, and with ratios of 7.7–11.7 and 10.5–13.7 for necrosis over peri-tumor tissue by autoradiography and fluorescence microscopy, respectively. In conclusion, NTRT improved the anticancer efficacy of VDT in rabbits with VX2 tumors. PMID:26036625

  6. Application of Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost Techniques to Prepare “Safe Margin” in the Rabbit VX2 Limb Tumor Model

    PubMed Central

    Wang, Chong-Wen; Zhou, Yang; Bai, Jing-Ping; Liu, Hao; Liu, Yan; Shi, Guang-Li; Ding, Jiao-Jiao; Ma, Dong-Hui; Li, Wen-Ting; Xie, Peng-Ming; Yan, Yue

    2015-01-01

    Background In this study, we aimed to establish the rabbit VX2 limb tumor model, and then prepare a “necrotic zone” as a safe margin by volumetric modulated arc therapy and simultaneous integrated boost (VMAT-SIB) technique applied in the areas where the tumor is located adjacent to the bone (GTVboost area). Material/Methods Rabbits in the control group (n=10) were not treated, while those in the test group (n=10) were treated with the SIB schedule delivering a dose of 40Gy, 35Gy, 30Gy, and 25Gy to the GTVboost, GTV (gross tumor volume), CTV (clinical target volume), and PTV (planning target volume) in 10 fractions. Magnetic resonance diffusion-weighted imaging (MRDWI), 3-dimensional power Doppler angiography (3D-PDA), and histological changes were observed after radiotherapy. Results After radiotherapy, the two groups showed a significant difference in the GTVboost area. In the test group, the tumor necrosis showed a significantly low signal in DWI and high signal in apparent diffusion coefficient (ADC) maps. The 3D-PDA observation showed that tumor vascular structures decreased significantly. Histological analysis demonstrated that a necrotic zone could be generated in the GTVboost area, and microscopic examination observed cell necrosis and fibroplasia. Conclusions This studies demonstrated the feasibility of using VMAT-SIB technique in the rabbit VX2 limb tumor model. The formation of a necrotic zone can be effectively defined as safe margin in the GTVboost area. showing potential clinical applicability. PMID:26280694

  7. NMR studies of metal-insulator transition in the spinel-type Cu(Ir1-xVx)2S4

    NASA Astrophysics Data System (ADS)

    Niki, H.; Okuda, H.; Okada, Y.; Higa, K.; Oshiro, M.; Fukuyoshi, N.; Mahoe, R.; Yogi, M.; Nakama, T.; Yagasaki, K.; Ebisu, S.; Nagata, S.

    2011-01-01

    In order to investigate the physical properties of a metal-insulator transition (MIT) on Ir rich side in Cu(Ir1-xVx)2S4 from a microscopic point of view, 63Cu NMR measurements for Cu(Ir1-xVx)2S4 (x = 0.00, 0.03 and 0.05) have been carried out from 4.2 to 300 K. The temperature dependences of the line width, Knight shift and spin-lattice relaxation time (T1) have been measured for these samples. A sudden decreases of the 1/T1T and the negative contribution to the Knight shift from the core polarization of Cu conduction electrons for x = 0.00 and 0.03 samples show clearly the existence of the MIT at TMI = 226 and 175 K, respectively, being attributed to the opening of a band gap below TMI. However, the temperature dependences of the 1/T1T and the Knight shift for x = 0.05 sample change continuously as the band gap is remarkably suppressed below TMI. The density of states at Fermi level in the insulating phase is reduced to about 20 % of that in the metallic phase.

  8. Electronic structure and optical properties of α-(Fe1-xVx)2O3 solid-solution thin films

    NASA Astrophysics Data System (ADS)

    Chamberlin, S. E.; Nayyar, I. H.; Kaspar, T. C.; Sushko, P. V.; Chambers, S. A.

    2015-01-01

    We have examined the effect of V doping on the electronic and optical properties of epitaxial hematite (α-Fe2O3) thin films, by employing several characterization techniques and computational modeling. The conductivity of α-(Fe1-xVx)2O3 (0 ≤ x ≤ ˜0.5) is enhanced by several orders of magnitude as x is increased, as evidenced by electrical resistivity measurements and x-ray photoelectron spectroscopy core-level and valence-band spectra. Optical absorption shows a reduction in the direct band gap by as much as 0.64 eV for x = 0.53 (Eg = 1.46 eV) relative to that of α-Fe2O3 (Eg = 2.10 eV). Detailed understanding of the character of the optical transitions in the alloys is achieved using first-principles calculations of the ground and excited states. These calculations reveal that V doping results in occupied V 3d orbitals hybridized with Fe orbitals and located at approximately mid-gap in α-Fe2O3. The lowest energy transitions involve charge transfer from occupied V 3d to unoccupied Fe 3d* orbitals. With a low band gap and high conductivity, α-(Fe1-xVx)2O3 is a promising material for photovoltaic and photoelectrochemical applications.

  9. Histological evaluation of high-intensity focused ultrasound with lower-intensity focused ultrasound pre-exposure on the treatment of rabbit VX2 liver tumors

    SciTech Connect

    Zou Hairong; Zou Jianzhong; Wang Yan; Ou Xia

    2012-10-03

    This study was to evaluate the effect of pre-exposure lower-intensity focused ultrasound(US), or LIFU, in high-intensity focused ultrasound(HIFU) ablation of rabbit VX2 liver tumors . Liver VX2 tumor models were established in 30 rabbits, which were divided randomly into two groups. The liver tumors of rabbits in Group A underwent single HIFU ablation; those in Group B were given LIFU exposure before HIFU treatment. Five rabbits from each of the two groups were sacrificed at 0 hours, 3 days, and 7 days after HIFU ablation. Tissue samples that included targeted and short-range sounding (s-RS, within 5 mm of the targeted) and far-range sounding (f-RS, more than 5 mm of the targeted) tissues were observed using light microscope and transmission electron microscopy. The histological examination indicated that not only the targeted tumor cells became irreversible damage, but also the short-range sounding tumors were severely damaged by the HIFU with LIFU pre-exposure in group B. It is concluded that LIFU pre-exposure can enhance the effects of HIFU ablation on the destruction of cell ultrastructures and can enlarge the region of HIFU ablation.

  10. Evaluation of the Therapeutic Efficacy of Sequential Therapy Involving Percutaneous Microwave Ablation in Combination with 131I-Hypericin Using the VX2 Rabbit Breast Solid Tumor Model

    PubMed Central

    Zhu, Miao; Lin, Xiao-An; Zha, Xiao-Ming; Zhou, Wen-Bin; Xia, Tian-Song; Wang, Shui

    2015-01-01

    Purpose Combination of percutaneous microwave ablation (PMWA) and intravenous injection of 131I-hypericin(IIIH) may bear potential as a mini-invasive treatment for tumor. The objective of this study was to assess the effect of PMWA and IIIH in breast tumor growth. Methods Ten New Zealand White rabbits bearing VX2 breast carcinomas were randomly divided into two groups (each 5 examples) and processed using PMWA followed by IIIH and IIIH alone. The IIIH activity was evaluated using planar scintigraphy, autoradiography and biodistribution analysis. The maximum effective safe dose of IIIH was found through 48 rabbits with VX2 breast tumor, which were randomized into six groups (n=8 per group). Subsequently, a further 75 rabbits bearing VX2 breast solid tumors were randomly divided into five groups (each 15 examples) and treated as follows: A, no treatment group; B, PMWA alone; C, IIIH alone; D, PMWA+IIIH×1 (at 8 h post-PMWA); and E, PMWA+IIIH×2 (at 8 h and at 8 days post-PMWA). The therapeutic effect was assessed by measurement of tumor size and performation of positron emission tomography/computed tomograph (PET/CT) scans, liver and renal function tests and Kaplan-Meier survival analysis. Results The planar scintigraphy findings suggested a significant uptake of 131I in necrotic tumor tissue. The autoradiography gray scales indicated higher selective uptake of IIIH by necrotic tissue, with significant differences between the groups with and those without necrotic tumor tissue (P<0.05). The maximum effective safe dose of IIIH was 1mCi/kg. The PET/CT scans and tumor size measurement suggested improvements in treatment groups at all time points (P<0.01). Significant differences were detected among Groups A, B, D and E (P<0.05). Lower levels of lung metastasis were detected in Groups D and E (P<0.05). There were no abnormalities in liver and renal functions tests or other reported side effects. Conclusion IIIH exhibited selective uptake by necrotic tumor tissue

  11. Structural perturbations of epitaxial α-(Fe1-xVx)2O3 thin films driven by excess oxygen near the surface

    NASA Astrophysics Data System (ADS)

    Chamberlin, S. E.; Kaspar, T. C.; Bowden, M. E.; Shutthanandan, V.; Kabius, B.; Heald, S.; Keavney, D. J.; Chambers, S. A.

    2014-12-01

    We examine the structure and composition of phase-pure epitaxial α-(Fe1-xVx)2O3 thin films deposited on α-Al2O3(0001) substrates by oxygen-plasma-assisted molecular beam epitaxy for 0 ≤ x ≤ ˜0.5. The films crystallize in the corundum lattice, with vanadium substituting for iron throughout. Vanadium cations exhibit the expected 3+ charge state in the bulk, but exhibit higher valences nearer to the surface, most likely because of excess oxygen in interstitial sites near the surface. The extent of vanadium oxidation beyond the 3+ state is inversely proportional to x. The gradation of vanadium valence with depth has an impact on local bonding geometries, and could be highly significant in this material's efficiency as a photocatalyst.

  12. Autoradiographic and histopathological studies of boric acid-mediated BNCT in hepatic VX2 tumor-bearing rabbits: Specific boron retention and damage in tumor and tumor vessels.

    PubMed

    Yang, C H; Lin, Y T; Hung, Y H; Liao, J W; Peir, J J; Liu, H M; Lin, Y L; Liu, Y M; Chen, Y W; Chuang, K S; Chou, F I

    2015-12-01

    Hepatoma is a malignant tumor that responds poorly to conventional therapies. Boron neutron capture therapy (BNCT) may provide a better way for hepatoma therapy. In this research, (10)B-enriched boric acid (BA, 99% (10)B) was used as the boron drug. A multifocal hepatic VX2 tumor-bearing rabbit model was used to study the mechanisms of BA-mediated BNCT. Autoradiography demonstrated that BA was selectively targeted to tumors and tumor vessels. Histopathological examination revealed the radiation damage to tumor-bearing liver was concentrated in the tumor regions during BNCT treatment. The selective killing of tumor cells and the destruction of the blood vessels in tumor masses may be responsible for the success of BA-mediated BNCT for liver tumors. PMID:26372198

  13. Structural perturbations of epitaxial α-(Fe1-xVx)2O3 thin films driven by excess oxygen near the surface

    SciTech Connect

    Chamberlin, Sara E.; Kaspar, Tiffany C.; Bowden, Mark E.; Shutthanandan, V.; Kabius, Bernd C.; Heald, Steve M.; Keavney, David; Chambers, Scott A.

    2014-12-21

    We examine the structure and composition of phase-pure epitaxial α-(Fe1-xVx)2O3 thin films deposited on α-Al2O3(0001) substrates by oxygen-plasma-assisted molecular beam epitaxy for 0 ≤ x ≤ ~0.5. The films crystallize in the corundum lattice, with vanadium substituting for iron throughout. Vanadium cations exhibit the expected 3+ charge state in the bulk, but exhibit higher valences nearer to the surface, most likely because of excess oxygen in interstitial sites near the surface. The extent of vanadium oxidation beyond the 3+ state is inversely proportional to x. The gradation of vanadium valence with depth may have an impact on local bonding geometries, and could be highly significant in this material’s efficiency as a photocatalyst.

  14. Percutaneous Tumor Ablation: Cryoablation Facilitates Targeting of Free Epirubicin-Ethanol-Ioversol Solution Interstitially Coinjected in a Rabbit VX2 Tumor Model.

    PubMed

    He, Xiaofeng; Xiao, Yueyong; Zhang, Xiao; Du, Peng; Zhang, Xin; Li, Jie; An, Yunxia; Le Pivert, Patrick

    2016-08-01

    This acute study was aimed at exploring the ability of a cryoablative lesion to drive the distribution of a concomitant in situ injection of a free epirubicin-ethanol-ethiodol-methylene blue mixture. We report the feasibility and safety of this new percutaneous computed tomography-guided combinatorial ablative procedure on VX2 tumors. Eight New Zealand white rabbits bearing 16 tumors on both side of the back muscle were randomly selected and treated on the same day with the following procedures: (1) 8 concomitant cryoablation and interstitial chemotherapy and (2) 8 intratumor marginal chemotherapy. For the latter, an injection needle was positioned at the inner distal margin of a first selected tumor side, where the chemotherapy was delivered during 5 serial sequences. For the concomitant therapy, a single cryoneedle maintained the ice front at the tumor margin, where a needle delivered the drug dose during 5 freeze-injection-thaw sequences. Enhanced computed tomography scans on days 3, 7, and 10 assessed the tumor contours and the tracer localization. Two rabbits were killed on days 0, 3, 7, and 10 for gross and histopathological analyses. During the concomitant therapy, ioversol was distributed at the tumor and iceball margins along with the methylene blue. Enhanced computed tomography on days 3, 7, and 10 showed a focal enlarging defect of the tumor marginal enhancing rim. The rim coincided with focal necrosis at histopathology. During the intratumor chemotherapy procedure, computed tomography showed that the tracers distributed mostly over the tumor mass. No marginal necrosis was detected at histopathology. On day 10, the tumor size for the intratumor chemotherapy group was twice that of the concomitant therapy group. No adverse events were observed. In this VX2 tumor model, our image-guided concomitant therapy is feasible and may enhance the effectiveness of a free epirubicin tracer mixture at the tumor margin. PMID:26206769

  15. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    PubMed Central

    2014-01-01

    Purpose: To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. Methods: This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. Results: CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Conclusion: Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US. PMID:24936491

  16. Dynamic Contrast-Enhanced MRI Using a Macromolecular MR Contrast Agent (P792): Evaluation of Antivascular Drug Effect in a Rabbit VX2 Liver Tumor Model

    PubMed Central

    Park, Hee Sun; Lee, Jeong Min; Kim, Young Il; Woo, Sungmin; Yoon, Jung Hwan; Choi, Jin-Young; Choi, Byung Ihn

    2015-01-01

    Objective To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. Materials and Methods This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. Results P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Conclusion Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent. PMID:26357497

  17. Radiotherapy for ocular tumours.

    PubMed

    Stannard, C; Sauerwein, W; Maree, G; Lecuona, K

    2013-02-01

    Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25-30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750

  18. Radiotherapy for ocular tumours

    PubMed Central

    Stannard, C; Sauerwein, W; Maree, G; Lecuona, K

    2013-01-01

    Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25–30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750

  19. Tumours of the ovary

    PubMed Central

    Nielsen, Svend W.; Misdorp, W.; McEntee, Kenneth

    1976-01-01

    Ovarian tumours are common in animals, the majority occurring in bitches and cows. The two most important germ cell tumours were dysgerminoma and teratoma; these morphologically resemble their counterparts in women, with the exception that teratomas in animals tend less to malignancy. The granulosa cell tumour is the most frequent sex cord-stromal tumour in all six species and it may contain luteinized areas or show differentiation towards a Sertoli cell pattern. The canine papillary adenoma and papillary adenocarcinoma, which are as common as granulosa tumours, have several features in common with their counterparts in women: they are of similar histological appearance, are frequently bilateral, and the adenocarcinomas have a great propensity for peritoneal implantation metastasis. Ovarian cysts are frequent in the bitch, sow, and cow and may originate from five different anatomical structures in the ovary. ImagesFig. 1Fig. 2 and 3Fig. 20-22Fig. 8-10Fig. 15 and 16Fig. 23Fig. 24Fig. 25Fig. 26Fig. 17-19Fig. 4 and 5Fig. 6 and 7Fig. 11Fig. 12Fig. 13 and 14 PMID:1086151

  20. Electronic structure and optical properties of α-(Fe1-xVx)2O3 solid-solution thin films

    SciTech Connect

    Chamberlin, Sara E.; Nayyar, Iffat H.; Kaspar, Tiffany C.; Sushko, Petr; Chambers, Scott A.

    2015-01-26

    We have examined the effect of V doping on the electronic and optical properties of hematite (α-Fe2O3) by means of α-(Fe1-xVx)2O3 (0 ≤ x ≤ ~0.5) epitaxial films and theoretical modeling. The conductivity is enhanced by several orders of magnitude as x is increased, and this enhancement is manifested in x-ray photoelectron spectra by a growing Doniach-Sunjic tail on the O 1s peak, as well as by increasing intensity at the Fermi level in valence band spectra. Optical absorption shows a reduction in direct band gap by as much as 0.64 eV for x = 0.53 (Eg = 1.46 eV) relative to that of α-Fe2O3 (Eg = 2.10 eV). Detailed understanding of the character of the optical transitions in the alloys is achieved using first-principles calculations of the ground and excited states. These calculations reveal that V doping results in localized, occupied V 3d states which are hybridized with Fe states and located at approximately mid-gap in α Fe2O3. The lowest energy transitions involve electronic excitations from occupied V 3d orbitals to unoccupied Fe 3d* orbitals.

  1. Structural and magnetic properties in the quantum S=1/2 dimer systems Ba3(Cr1-xVx)2O8 with site disorder

    SciTech Connect

    Hong, Tao; Zhu, L. Y.; Ke, X.; Garlea, Vasile O; Qiu, Y.; Yoshizawa, H.; Zhu, M.; Granroth, Garrett E; Savici, Andrei T; Gai, Zheng; Zhou, H. D.

    2013-01-01

    We report a comprehensive study of the DC susceptibility, specific heat, neutron diffraction, and inelastic neutron scattering measurements on the polycrystalline Ba3(Cr1-xVx)2O8 samples, where x=0, 0.06, 0.15, and 0.53. A Jahn-Teller structure transition occurs for x=0, 0.06, and 0.15 samples and the transition temperature is reduced upon vanadium substitution from 70(2) K at x=0 to 60(2) K at x=0.06 and 0.15. The structure becomes less distorted as x increases and such transition disappears at x=0.53. The observed magnetic excitation spectrum indicates that the singlet ground state remains unaltered and spin gap energy =1.3(1) meV is identical within the instrument resolution for all x. In addition, the dispersion bandwidth W decreases with increase of x. At x=0.53, W is reduced to 1.4(1) meV from 2.0(1) meV at x=0.

  2. The influence of microscopic parameters on the ionic conductivity of SrBi2(Nb1-xVx)2O9-δ(0≤x≤0.3) ceramics

    NASA Astrophysics Data System (ADS)

    Harihara Venkataraman, B.; Varma, K. B. R.

    2005-10-01

    Layered SrBi2(Nb1-xVx)2O9-δ (SBVN) ceramics with x lying in the range 0 0.3 (30 mol%) were fabricated by the conventional sintering technique. The microstructural studies confirmed the truncating effect of V2O5 on the abnormal platy growth of SBN grains. The electrical conductivity studies were centred in the 573 823 K as the Curie temperature lies in this range. The concentration of mobile charge carriers (n), the diffusion constant (D0) and the mean free path (a) were calculated by using Rice and Roth formalism. The conductivity parameters such as ion-hopping rate (ωp) and the charge carrier concentration (K‧) term have been calculated using Almond and West formalism. The aforementioned microscopic parameters were found to be V2O5 content dependent on SrBi2(Nb1-xVx)2O9-δ ceramics.

  3. Radiofrequency Ablation Before Intratumoral Injection of 131I-chTNT Improves the Tumor-to-Normal Tissue Ratio in Solid VX2 Tumor

    PubMed Central

    Zheng, Shu-Guang; Lu, Ming-De; Yue, Dian-Chao; Xie, Xiao-Yan; Liu, Guang-Jian

    2013-01-01

    Abstract Purpose This study was aimed to investigate whether the tumor necrosis induced by radiofrequency ablation (RFA) can improve the ratio of tumor-to-normal tissue (T/NT) after intratumoral injection of 131I-chTNT. Materials and Method Eighteen New Zealand rabbits bearing VX2 tumor on the thigh were randomly divided into two treatment groups (control group: intratumoral injection of 131I-chTNT alone; RFA group: RFA + intratumoral injection of 131I-chTNT 3 days after RFA) and each group was further divided into three subgroups I, II, and III (1–2 cm, 2–3 cm, and 3–4 cm in maximum diameter, respectively), by the tumor size. SPECT was performed to evaluate the T/NT on days 1, 8, and 15 after 131I-chTNT injection. Results After treatment, all rabbits underwent the SPECT whole-body scan and the T/NT was analyzed. The results showed that T/NT in the RFA group (55.45±41.83) was significantly higher compared with the control group (7.23±5.61) (F=18.89, p=0.001). Meanwhile, a linear ascending trend was found for T/NT in the RFA group along with the follow-up time (r=0.47, p=0.01). The tumor size or the dose of 131I-TNT injection had no significant effect on the variation of T/NT in both groups (p>0.05). Conclusion RFA before intratumoral injection of 131I-chTNT can dramatically improve T/NT, demonstrating the potential application of this combination therapy. PMID:23964639

  4. Tumor Uptake of Hollow Gold Nanospheres after Intravenous and Intra-arterial Injection: PET/CT Study in a Rabbit VX2 Liver Cancer Model

    PubMed Central

    Tian, Mei; Lu, Wei; Zhang, Rui; Xiong, Chiyi; Ensor, Joe; Nazario, Javier; Jackson, James; Shaw, Colette; Dixon, Katherine A.; Miller, Jennifer; Wright, Kenneth; Li, Chun; Gupta, Sanjay

    2014-01-01

    Purpose This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model. Materials and Methods Fifteen VX2 tumor-bearing rabbits were randomized into five groups (N=3 in each group) that received either IV 64Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA 64Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated 64Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated 64Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA 64Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 hour after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 hours after injection, and tissues were evaluated for radioactivity. Results At 1 hour after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 hours after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 hours, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 %ID/g vs. 0.099 %ID/g; P < 0.001). Conclusion Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection. PMID:23608932

  5. Feasibility of Using Volumetric Contrast-Enhanced Ultrasound with a 3-D Transducer to Evaluate Therapeutic Response after Targeted Therapy in Rabbit Hepatic VX2 Carcinoma.

    PubMed

    Kim, Jeehyun; Kim, Jung Hoon; Yoon, Soon Ho; Choi, Won Seok; Kim, Young Jae; Han, Joon Koo; Choi, Byung-Ihn

    2015-12-01

    The aim of this study was to assess the feasibility of using dynamic contrast-enhanced ultrasound (DCE-US) with a 3-D transducer to evaluate therapeutic responses to targeted therapy. Rabbits with hepatic VX2 carcinomas, divided into a treatment group (n = 22, 30 mg/kg/d sorafenib) and a control group (n = 13), were evaluated with DCE-US using 2-D and 3-D transducers and computed tomography (CT) perfusion imaging at baseline and 1 d after the first treatment. Perfusion parameters were collected, and correlations between parameters were analyzed. In the treatment group, both volumetric and 2-D DCE-US perfusion parameters, including peak intensity (33.2 ± 19.9 vs. 16.6 ± 10.7, 63.7 ± 20.0 vs. 30.1 ± 19.8), slope (15.3 ± 12.4 vs. 5.7 ± 4.5, 37.3 ± 20.4 vs. 15.7 ± 13.0) and area under the curve (AUC; 1004.1 ± 560.3 vs. 611.4 ± 421.1, 1332.2 ± 708.3 vs. 670.4 ± 388.3), had significantly decreased 1 d after the first treatment (p = 0.00). In the control group, 2-D DCE-US revealed that peak intensity, time to peak and slope had significantly changed (p < 0.05); however, volumetric DCE-US revealed that peak intensity, time-intensity AUC, AUC during wash-in and AUC during wash-out had significantly changed (p = 0.00). CT perfusion imaging parameters, including blood flow, blood volume and permeability of the capillary vessel surface, had significantly decreased in the treatment group (p = 0.00); however, in the control group, peak intensity and blood volume had significantly increased (p = 0.00). It is feasible to use DCE-US with a 3-D transducer to predict early therapeutic response after targeted therapy because perfusion parameters, including peak intensity, slope and AUC, significantly decreased, which is similar to the trend observed for 2-D DCE-US and CT perfusion imaging parameters. PMID:26365926

  6. Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer

    PubMed Central

    Nilsson, Maria; Adamo, Hanibal; Bergh, Anders; Halin Bergström, Sofia

    2016-01-01

    Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour-suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients. PMID:26804196

  7. Targeting ALCAM in the cryo-treated tumour microenvironment successfully induces systemic anti-tumour immunity.

    PubMed

    Kudo-Saito, Chie; Fuwa, Takafumi; Kawakami, Yutaka

    2016-07-01

    Cryoablative treatment has been widely used for treating cancer. However, the therapeutic efficacies are still controversial. The molecular mechanisms of the cryo-induced immune responses, particularly underlying the ineffectiveness, remain to be fully elucidated. In this study, we identified a new molecular mechanism involved in the cryo failure. We used cryo-ineffective metastatic tumour models that murine melanoma B16-F10 cells were subcutaneously and intravenously implanted into C57BL/6 mice. When the subcutaneous tumours were treated cryoablation on day 7 after tumour implantation, cells expressing activated leucocyte cell adhesion molecule (ALCAM/CD166) were significantly expanded not only locally in the treated tumours but also systemically in spleen and bone marrow of the mice. The cryo-induced ALCAM(+) cells including CD45(-) mesenchymal stem/stromal cells, CD11b(+)Gr1(+) myeloid-derived suppressor cells, and CD4(+)Foxp3(+) regulatory T cells significantly suppressed interferon γ production and cytotoxicity of tumour-specific CD8(+) T cells via ALCAM expressed in these cells. This suggests that systemic expansion of the ALCAM(+) cells negatively switches host-immune directivity to the tumour-supportive mode. Intratumoural injection with anti-ALCAM blocking monoclonal antibody (mAb) following the cryo treatment systemically induced tumour-specific CD8(+) T cells with higher cytotoxic activities, resulting in suppression of tumour growth and metastasis in the cryo-resistant tumour models. These suggest that expansion of ALCAM(+) cells is a determinant of limiting the cryo efficacy. Further combination with an immune checkpoint inhibitor anti-CTLA4 mAb optimized the anti-tumour efficacy of the dual-combination therapy. Targeting ALCAM may be a promising strategy for overcoming the cryo ineffectiveness leading to the better practical use of cryoablation in clinical treatment of cancer. PMID:27208904

  8. The Laser Treatment of Experimental Malignant Tumours

    PubMed Central

    McGuff, Paul E.; Deterling, Ralph A.; Gottlieb, Leonard S.; Fahimi, H. Dariush; Bushnell, David; Roeber, Fred

    1964-01-01

    Some of the results of experiments performed during the past two years to assess effects of laser energy on experimental malignant tumours are reviewed. Twenty types of malignant tumours (most in the cheek pouch and 11 of human origin) were treated in over 700 Syrian hamsters. Results of laser treatment of malignant melanomas and thyroidal carcinomas are presented. A human patient with malignant melanoma treated by laser energy is described. Investigation of thermal effect revealed that the laser-treated tumour remained warm for about one minute, while the cautery-treated tumour cooled to normal temperature in five seconds. Direct action of laser on superficial tumours is possible; deeper lesions must be exposed surgically. Laser energy has a selective effect on certain malignant tumours, resulting in their progressive regression and ultimate dissolution. All hamsters with implanted malignant melanomas and carcinomas of human origin, after completion of a course of laser treatment, showed no gross or histologic evidence of tumour up to the date of last observation. ImagesFig. 1Fig. 2aFig. 2bFig. 2cFig. 2dFig. 2eFig. 2fFig. 3Fig. 4aFig. 4bFig. 4cFig. 4dFig. 4eFig. 4fFig. 4gFig. 6 PMID:14229757

  9. Anti-Angiogenesis Therapy in the Vx2 Rabbit Cancer Model with a Lipase-cleavable Sn 2 Taxane Phospholipid Prodrug using αvβ3-Targeted Theranostic Nanoparticles

    PubMed Central

    Pan, Dipanjan; Schmieder, Anne H.; Wang, Kezheng; Yang, Xiaoxia; Senpan, Angana; Cui, Grace; Killgore, Kendall; Kim, Benjamin; Allen, John S.; Zhang, Huiying; Caruthers, Shelton D.; Shen, Baozhong; Wickline, Samuel A.; Lanza, Gregory M.

    2014-01-01

    In nanomedicine, the hydrophobic nature of paclitaxel has favored its incorporation into many nanoparticle formulations for anti-cancer chemotherapy. At lower doses taxanes are reported to elicit anti-angiogenic responses. In the present study, the facile synthesis, development and characterization of a new lipase-labile docetaxel prodrug is reported and shown to be an effective anti-angiogenic agent in vitro and in vivo. The Sn 2 phosphatidylcholine prodrug was stably incorporated into the lipid membrane of αvβ3-integrin targeted perfluorocarbon (PFC) nanoparticles (αvβ3-Dxtl-PD NP) and did not appreciably release during dissolution against PBS buffer or plasma over three days. Overnight exposure of αvβ3-Dxtl-PD NP to plasma spiked with phospholipase enzyme failed to liberate the taxane from the membrane until the nanoparticle integrity was compromised with alcohol. The bioactivity and efficacy of αvβ3-Dxtl-PD NP in endothelial cell culture was as effective as Taxol® or free docetaxel in methanol at equimolar doses over 96 hours. The anti-angiogenesis effectiveness of αvβ3-Dxtl-PD NP was demonstrated in the Vx2 rabbit model using MR imaging of angiogenesis with the same αvβ3-PFC nanoparticle platform. Nontargeted Dxtl-PD NP had a similar MR anti-angiogenesis response as the integrin-targeted agent, but microscopically measured decreases in tumor cell proliferation and increased apoptosis were detected only for the targeted drug. Equivalent dosages of Abraxane® given over the same treatment schedule had no effect on angiogenesis when compared to control rabbits receiving saline only. These data demonstrate that αvβ3-Dxtl-PD NP can reduce MR detectable angiogenesis and slow tumor progression in the Vx2 model, whereas equivalent systemic treatment with free taxane had no benefit. PMID:24723979

  10. Site-specific volumetric analysis of lung tumour motion

    NASA Astrophysics Data System (ADS)

    Pepin, Eric W.; Wu, Huanmei; Sandison, George A.; Langer, Mark; Shirato, Hiroki

    2010-06-01

    The treatment of lung cancer with radiation therapy is hindered by respiratory motion. Real-time adjustments to compensate for this motion are hampered by mechanical system latencies and imaging-rate restrictions. To better understand tumour motion behaviour for adaptive image-guided radiation therapy of lung cancer, the volume of a tumour's motion space was investigated. Motion data were collected by tracking an implanted fiducial using fluoroscopy at 30 Hz during treatment sessions. A total of 637 treatment fractions from 31 tumours were used in this study. For each fraction, data points collected from three consecutive breathing cycles were used to identify instantaneous tumour location. A convex hull was created over these data points, defining the tumour motion envelope. The study sought a correlation between the tumour location in the lung and the convex hull's volume and shape. It was found that tumours located in the upper apex had smaller motion envelopes (<50 mm3), whereas tumours located near the chest wall or diaphragm had larger envelopes (>70 mm3). Tumours attached to fixed anatomical structures had small motion spaces. Three general shapes described the tumour motion envelopes: 50% of motion envelopes enclosed largely 1D oscillation, 38% enclosed an ellipsoid path, 6% enclosed an arced path and 6% were of hybrid shape. This location-space correlation suggests it may be useful in developing a predictive model, but more work needs to be done to verify it.

  11. Brain and spinal tumour.

    PubMed

    Goh, C H; Lu, Y Y; Lau, B L; Oy, J; Lee, H K; Liew, D; Wong, A

    2014-12-01

    This study reviewed the epidemiology of brain and spinal tumours in Sarawak from January 2009 till December 2012. The crude incidence of brain tumour in Sarawak was 4.6 per 100,000 population/year with cumulative rate 0.5%. Meningioma was the most common brain tumour (32.3%) and followed by astrocytoma (19.4%). Only brain metastases showed a rising trend and cases were doubled in 4 years. This accounted for 15.4% and lung carcinoma was the commonest primary. Others tumour load were consistent. Primitive neuroectodermal tumour (PNET) and astrocytoma were common in paediatrics (60%). We encountered more primary spinal tumour rather than spinal metastases. Intradural schwannoma was the commonest and frequently located at thoracic level. The current healthcare system in Sarawak enables a more consolidate data collection to reflect accurate brain tumours incidence. This advantage allows subsequent future survival outcome research and benchmarking for healthcare resource planning. PMID:25934956

  12. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  13. The studies about doxorubicin-loaded p(N-isopropyl-acrylamide-co-butyl methylacrylate) temperature-sensitive nanogel dispersions on the application in TACE therapies for rabbit VX2 liver tumor.

    PubMed

    Qian, Kun; Ma, Yingying; Wan, Jiangshan; Geng, Shinan; Li, Han; Fu, Qianwen; Peng, Xiaole; Kan, Xuefeng; Zhou, Guofeng; Liu, Wei; Xiong, Bin; Zhao, Yanbing; Zheng, Chuansheng; Yang, Xiangliang; Xu, HuiBi

    2015-08-28

    Transarterial chemo-embolization (TACE), which combined embolization therapy and chemotherapy, has become the most widely used treatment for unresectable liver cancer. Blood-vessel-embolic materials play key role on TACE. In the present work, doxorubicin-loaded p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels-iohexol dispersions (IBi-D) were reported firstly for TACE therapy to liver cancer. Using inverting-vial method, IBi-D dispersions showed three phases (swollen gel, flowable sol and shrunken gel) as temperature increased. Although Dox had little effect on the CGTs between flowable and shrunken gel, the rheological properties of IBi-D dispersions could greatly improved by Dox. A sustained Dox-release, which was necessary in TACE therapy, was found from IBi-D dispersions in the eluting medium of PBS buffers. The studies about renal artery embolization of normal rabbits indicated that IBi-D dispersions showed good properties in embolizing all kinds of renal arteries (including peripheral, small and large arteries) by controlling their injecting dosages. Angiography and medical evaluation indicated that TACE therapy of IBi-D dispersions has better efficacy on rabbit VX2 liver tumors than TAC treatment of free Dox and TAE treatment of IBi dispersions. PMID:26079186

  14. Crossover from antiferro-to-ferromagnetism on substitution of Co by V in RE(Co1-xVx)2Si2 (0 ≤ x ≤ 0.35)

    NASA Astrophysics Data System (ADS)

    Chowdhury, Rajeswari Roy; Dhara, Susmita; Bandyopadhyay, Bilwadal

    2015-06-01

    In PrCo2Si2 and NdCo2Si2, Co has been partially substituted by V. Vanadium having a larger atomic radius than cobalt, the substitution results in a negative pressure affecting the magnetic properties of the compound. The samples RE(Co1-xVx)2Si2 (RE = Pr, Nd; x = 0, 0.20, 0.35) were prepared by melting the corresponding elements in arc furnace and characterized using x-ray diffraction. Magnetometric measurements show that the parent compounds PrCo2Si2 and NdCo2Si2 are antiferromagnetic, as reported. With doping, ferrimagnetic behaviour is observed from temperature dependence of inverse susceptibility at about 50 K. At lower than 30 K, the magnetizations tend to saturate at high fields. From the field dependence of magnetization, the hysteresis loops and also coercive fields as observed, the samples exhibit ferromagnetism below ˜ 30 K. Exchange bias effect is also observed in the high V containing sample. The specific heat studies of the samples show transitions consistent with the magnetization data. Pr(Co0.65V0.35)2Si2 and Nd(Co0.65V0.35)2Si2 show magnetoresistance (MR) of ˜ 25% and 15%, respectively, at 4 K and 9 tesla.

  15. Nanoparticle distribution and temperature elevations in prostatic tumours in mice during magnetic nanoparticle hyperthermia.

    PubMed

    Attaluri, Anilchandra; Ma, Ronghui; Qiu, Yun; Li, Wei; Zhu, Liang

    2011-01-01

    Among a variety of hyperthermia methods, magnetic nanoparticle hyperthermia is a highly promising approach for its confined heating within the tumour. In this study we perform in vivo animal experiments on implanted prostatic tumours in mice to measure temperature distribution in the tumour during magnetic nanoparticle hyperthermia. Temperature elevations are induced by a commercially available ferrofluid injected via a single injection to the centre of the tumour, when the tumour is subject to an alternating magnetic field. Temperature mapping in the tumours during magnetic nanoparticle hyperthermia has demonstrated the feasibility of elevating tumour temperatures higher than 50°C using only 0.1 cm(3) ferrofluid injected in the tumour under a relatively low magnetic field (3 kA/m). Detailed 3-D nanoparticle concentration distribution is quantified using a high-resolution microCT imaging system. The calculated nanoparticle distribution volume based on the microCT scans is useful to analyse nanoparticle deposition in the tumours. Slower ferrofluid infusion rates result in smaller nanoparticle distribution volumes in the tumours. Nanoparticles are more confined in the vicinity of the injection site with slower infusion rates, causing higher temperature elevations in the tumours. The increase in the nanoparticle distribution volume in the tumour group after the heating from that in the tumour group without heating suggests possible nanoparticle re-distribution in the tumours during the heating. PMID:21756046

  16. Tumours of the lung

    PubMed Central

    Stünzi, H.; Head, K. W.; Nielsen, S. W.

    1974-01-01

    Lung tumours are not common in domestic animals; there has not been the increase in epidermoid carcinomas and anaplastic small-cell carcinomas that has occurred in man this century. Adenocarcinoma is the most common type in animals. The biological behaviour of each type of tumour in animals seems to be much the same as in man. The tumours are described histologically, the main categories being: epidermoid carcinoma, anaplastic carcinoma, adenocarcinoma, combined epidermoid and adenocarcinoma, carcinoid tumours, bronchial gland tumours, benign tumours, and sarcomas. ImagesFig. 13Fig. 14Fig. 15Fig. 16Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12 PMID:4371738

  17. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  18. In vivo 31P nuclear magnetic resonance spectroscopy of experimental murine tumours and human tumour xenografts: effects of blood flow modification.

    PubMed Central

    Bremner, J. C.; Counsell, C. J.; Adams, G. E.; Stratford, I. J.; Wood, P. J.; Dunn, J. F.; Radda, G. K.

    1991-01-01

    The effect of hydralazine on tumours appears to vary depending on tumour type. Blood flow and radiation sensitivity decrease more in murine tumours than human tumour xenografts. In this study a comparison between various tumour types has been made using in vivo 31P nuclear magnetic resonance spectroscopy (NMRS) to follow the metabolic responses occurring after clamping or intravenous administration of hydralazine (5 mg kg-1). Large increases in the Pi/total phosphate ratio were found with the murine sarcomas, KHT and RIF-1 implanted into C3H/He mice. However little or no effect was seen for the two human xenografted tumours, HX118 and HT29 implanted in MFI nu/nu/01a mice. An intermediate response was observed for KHT tumours grown in nu/nu mice. All tumours showed a large response to clamping. The anaesthetic Hypnorm/Hypnovel has a great influence on the response of the tumour metabolism to hydralazine appearing to both prolong and increase the changes induced. There is evidence to support the theory that the changes in 31P spectra are related to the oxygen status of the tumours. PMID:1931606

  19. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres

    NASA Astrophysics Data System (ADS)

    Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D.; Valmikinathan, Chandra M.; Mukhatyar, Vivek J.; Vakharia, Ajit; Pai, S. Balakrishna; Brahma, Barunashish; MacDonald, Tobey J.; Bellamkonda, Ravi V.

    2014-03-01

    Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.

  20. Tumour ablation: technical aspects

    PubMed Central

    Bodner, Gerd; Bale, Reto

    2009-01-01

    Abstract Image-guided percutaneous radiofrequency ablation (RFA) is a minimally invasive, relatively low-risk procedure for tumour treatment. Local recurrence and survival rates depend on the rate of complete ablation of the entire tumour including a sufficient margin of surrounding healthy tissue. Currently a variety of different RFA devices are available. The interventionalist must be able to predict the configuration and extent of the resulting ablation necrosis. Accurate planning and execution of RFA according to the size and geometry of the tumour is essential. In order to minimize complications, individualized treatment strategies may be necessary for tumours close to vital structures. This review examines the state-of-the art of different device technologies, approaches, and treatment strategies for percutaneous RFA of liver tumours. PMID:19965296

  1. Mouse Models of Brain Metastasis for Unravelling Tumour Progression.

    PubMed

    Soto, Manuel Sarmiento; Sibson, Nicola R

    2016-01-01

    Secondary tumours in the brain account for 40 % of triple negative breast cancer patients, and the percentage may be higher at the time of autopsy. The use of in vivo models allow us to recapitulate the molecular mechanisms potentially used by circulating breast tumour cells to proliferate within the brain.Metastasis is a multistep process that depends on the success of several stages including cell evasion from the primary tumour, distribution and survival within the blood stream and cerebral microvasculature, penetration of the blood-brain barrier and proliferation within the brain microenvironment. Cellular adhesion molecules are key proteins involved in all of the steps in the metastatic process. Our group has developed two different in vivo models to encompass both seeding and colonisation stages of the metastatic process: (1) haematogenous dissemination of tumour cells by direct injection into the left ventricle of the heart, and (2) direct implantation of the tumour cells into the mouse brain.This chapter describes, in detail, the practical implementation of the intracerebral model, which can be used to analyse tumour proliferation within a specific area of the central nervous system and tumour-host cell interactions. We also describe the use of immunohistochemistry techniques to identify, at the molecular scale, tumour-host cell interactions, which may open new windows for brain metastasis therapy. PMID:27325270

  2. Evidence of ferromagnetism in vanadium substituted layered intermetallic compounds RE (Co1-xVx) 2 Si2 (RE=Pr and Nd; 0 ≤ x ≤ 0.35)

    NASA Astrophysics Data System (ADS)

    Chowdhury, R. Roy; Dhara, S.; Bandyopadhyay, B.

    2016-03-01

    In intermetallic compounds RECo2Si2 (RE=Pr and Nd), cobalt has been partially substituted by vanadium to obtain RE(Co1-xVx)2Si2 (0 ≤ x ≤ 0.35). The parent compounds are antiferromagnetic below about 30 K due to the ordering of localized magnetic moments that are present only on rare-earth ions, cobalt being non-magnetic in the parent compounds. The present study demonstrates that in these compounds where 3 d and 4 f ions occupy different layers in the crystal structure, V substitution and subsequent lattice expansion results in the occurrence of inequivalent magnetic ions and complex interactions that lead to multiple magnetic transitions. At temperatures around 40-50 K, the temperature dependence of magnetization indicates a ferrimagnetic transition which is accompanied by a rapid decrease in the temperature dependence of resistivity. Below temperatures ∼30 K, the samples begin to show ferromagnetic-like behavior with the appearance of a coercive field and saturation in the magnetization at magnetic fields above ∼2 T. These two magnetic transitions are indicated also by prominent λ-like peaks in specific heat measurements. At around 10 K, a sharp drop in the resistivity indicates another magnetic transition which is followed by a rapid increase in coercive field with decrease in temperature. In a magnetic field of 9 T, the latter transition shifts to a lower temperature and that leads to a positive magnetoresistance. The onset of ferromagnetism at ∼30 K is accompanied with an exchange bias field which is observed for the first time in layered intermetallic compounds. The exchange bias field increases rapidly below the transition at ∼10 K and reaches ∼16% of coercive field at 2 K.

  3. In vivo EIS characterization of tumour tissue properties is dominated by excess extracellular fluid

    NASA Astrophysics Data System (ADS)

    Skourou, Christina; Rohr, Andreas; Hoopes, P. Jack; Paulsen, Keith D.

    2007-01-01

    Electrical impedance spectroscopy (EIS) is a non-ionizing, non-invasive technique which can be used to detect the presence of malignant tumours based on their electrical properties. Although it has been suggested that the edema which accompanies tumours strongly influences EIS tumour characterization, such information has not, until now, been documented in the literature. Growing intramuscular rodent tumours were imaged using magnetic resonance imaging (MRI) and EIS at several time points post-tumour implantation. The amount of edema associated with the tumours was calculated from the MRI images. Electrical parameters (resistivity, permittivity, fluid index ratio and peak frequency) were extracted from the EIS spectra. Taken together, the resulting electrical parameters strongly indicate that edema is the dominating pathological feature in EIS characterization and can at times conceal the presence of the tumour. Receiver operating characteristic analysis supports these findings.

  4. Iodine-125 brachytherapy for brain tumours - a review

    PubMed Central

    2012-01-01

    Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even though the physical and biological characteristics make these implants particularly attractive for minimal invasive treatment, the place for stereotactic brachytherapy is still poorly defined. An extensive review of the literature has been performed, especially concerning indications, results and complications. Iodine-125 seeds have been implanted in astrocytomas I-III, glioblastomas, metastases and several other tumour entities. Outcome data given in the literature are summarized. Complications are rare in carefully selected patients. All in all, for highly selected patients with newly diagnosed or recurrent primary or metastatic tumours, this method provides encouraging survival rates with relatively low complication rates and a good quality of life. PMID:22394548

  5. Gastrointestinal stromal tumour.

    PubMed

    Joensuu, Heikki; Hohenberger, Peter; Corless, Christopher L

    2013-09-14

    Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms that arise in the gastrointestinal tract, usually in the stomach or the small intestine and rarely elsewhere in the abdomen. They can occur at any age, the median age being 60-65 years, and typically cause bleeding, anaemia, and pain. GISTs have variable malignant potential, ranging from small lesions with a benign behaviour to fatal sarcomas. Most tumours stain positively for the mast/stem cell growth factor receptor KIT and anoctamin 1 and harbour a kinase-activating mutation in either KIT or PDGFRA. Tumours without such mutations could have alterations in genes of the succinate dehydrogenase complex or in BRAF, or rarely RAS family genes. About 60% of patients are cured by surgery. Adjuvant treatment with imatinib is recommended for patients with a substantial risk of recurrence, if the tumour has an imatinib-sensitive mutation. Tyrosine kinase inhibitors substantially improve survival in advanced disease, but secondary drug resistance is common. PMID:23623056

  6. Transport processes in tumours.

    PubMed

    Quastel, J H

    1965-12-01

    The characteristic features of transport systems controlling influx into tumour cells of nutrients and other chemicals are briefly described. Two notable features of transport of amino acids into tumour cells have been observed: extensive accumulation against a concentration gradient and equal accumulations, whether conditions are aerobic or anaerobic, provided glucose is present. This combination of features has not been observed in the majority of normal mammalian tissues so far examined. Important for considerations of chemotherapy is the ability of tumour transport carriers to transfer substances related in structure to amino acids and other nutrients. Amino acid analogues, for example, can either block transport of natural amino acids or can be transported into the cell where they may interfere with various aspects of amino acid metabolism. The study of transport carriers is essential for an understanding of tumour-host relationships and for considerations of chemotherapy. PMID:5842595

  7. In vivo longitudinal photoacoustic imaging of subcutaneous tumours in mice

    NASA Astrophysics Data System (ADS)

    Laufer, Jan; Johnson, Peter; Zhang, Edward; Treeby, Bradley; Cox, Ben; Pedley, Barbara; Beard, Paul

    2011-03-01

    Photoacoustic tomography can provide high resolution 3D images of vascular networks, making it well suited to characterising the development of tumour vasculature and its response to treatment. In this study, photoacoustic images to depths of up to 9 mm were obtained using an all optical ultrasound detection scheme. Two type of colorectal tumours (LS174T and SW1222) implanted subcutaneously in a mouse were studied. 3D photoacoustic images were obtained in vivo revealing the different vascular architectures of each tumour type and their evolution over a period of several days. The results suggest that photoacoustic imaging could play a role in providing essential pre-clinical information on tumour pathophysiology and eliciting the biological mechanisms underlying anti-angiogenic therapies and other treatments.

  8. Cochlear Implants.

    ERIC Educational Resources Information Center

    Clark, Catherine; Scott, Larry

    This brochure explains what a cochlear implant is, lists the types of individuals with deafness who may be helped by a cochlear implant, describes the process of evaluating people for cochlear implants, discusses the surgical process for implanting the aid, traces the path of sound through the cochlear implant to the brain, notes the costs of…

  9. Breast tumour angiogenesis

    PubMed Central

    Fox, Stephen B; Generali, Daniele G; Harris, Adrian L

    2007-01-01

    The central importance of tumour neovascularization has been emphasized by clinical trials using antiangiogenic therapy in breast cancer. This review gives a background to breast tumour neovascularization in in situ and invasive breast cancer, outlines the mechanisms by which this is achieved and discusses the influence of the microenvironment, focusing on hypoxia. The regulation of angiogenesis and the antivascular agents that are used in an antiangiogenic dosing schedule, both novel and conventional, are also summarized. PMID:18190723

  10. [Tumours and liver transplants].

    PubMed

    Mejzlík, Vladimír; Husová, Libuše; Kuman, Milan; Štěpánková, Soňa; Ondrášek, Jiří; Němec, Petr

    2015-01-01

    Liver transplantation as a curative treatment method can be used for selected primary liver tumours, in particular for hepatocellular carcinoma and rather rare semi-malignant tumours such as epithelioid hemangioendothelioma, further for infiltration of liver by metastatic neuroendocrine tumours (provided that metastases are only located in the liver and the primary tumour was removed) and for benign tumours (hemangiomas and adenomas) with oppression symptoms and size progression. Cholangiocarcinoma is not indicated for liver transplantation at the CKTCH Brno. In recent years liver transplants for hepatocellular carcinoma have increased and hepatocellular carcinoma has also been more frequently found ex post, in the explanted livers. Liver transplantation is indicated in selected patients with a good chance of long-term survival after liver transplantation (a generally accepted limit is 5 year survival of 50 % after transplantation). By 20 March 2015 there were liver transplants carried out on 38 patients - in 25 of them was hepatocellular carcinoma diagnosed before transplantation and in 13 it was found in the liver explants. 5 year survival following transplantation is reached by 53 % of this cohort. 32 % patients suffered from chronic hepatitis C. The longest surviving (32 years) patient at CKTCH Brno had liver transplanted for a big fibrolamellar hepatocellular carcinoma, which points to the prognostic significance of tumour histology: the criterion only considered in some indication schemes for practical reasons. Benign liver tumours (adenomatosis, cystadenoma, hemangioma with oppression symptoms) are rather rare indications and the transplantation results are favourable. 4 patients underwent transplantation for infiltration of liver by carcinoid, tumour recurrence occurred in one. PMID:26375706

  11. Testicular germ cell tumours.

    PubMed

    Rajpert-De Meyts, Ewa; McGlynn, Katherine A; Okamoto, Keisei; Jewett, Michael A S; Bokemeyer, Carsten

    2016-04-23

    Testicular germ cell tumours are at the crossroads of developmental and neoplastic processes. Their cause has not been fully elucidated but differences in incidences suggest that a combination of genetic and environment factors are involved, with environmental factors predominating early in life. Substantial progress has been made in understanding genetic susceptibility in the past 5 years on the basis of the results of large genome-wide association studies. Testicular germ cell tumours are highly sensitive to radiotherapy and chemotherapy and hence have among the best outcomes of all tumours. Because the tumours occur mainly in young men, preservation of reproductive function, quality of life after treatment, and late effects are crucial concerns. In this Seminar, we provide an overview of advances in the understanding of the epidemiology, genetics, and biology of testicular germ cell tumours. We also summarise the consensus on how to treat testicular germ cell tumours and focus on a few controversies and improvements in the understanding of late effects of treatment and quality of life for survivors. PMID:26651223

  12. Oral administration of Aloe vera and honey reduces Walker tumour growth by decreasing cell proliferation and increasing apoptosis in tumour tissue.

    PubMed

    Tomasin, Rebeka; Gomes-Marcondes, Maria Cristina Cintra

    2011-04-01

    Cancer is diagnosed in approximately 11 million people and is responsible for almost 8 million deaths worldwide every year. Research in cancer control has shown the importance of co-adjuvant therapies. Aloe vera may reduce tumour mass and metastasis rates, while honey may inhibit tumour growth. This study verified the influence of Aloe vera and honey on tumour growth and in the apoptosis process by assessing tumour size, the cell proliferation rate (Ki67-LI) and Bax/Bcl-2 expression at 7, 14 and 20 days after Walker 256 carcinoma implant in Wistar rats distributed into two groups: the WA group - tumour-bearing rats that received a gavage with a 670 µL/kg dose of Aloe vera and honey solution daily, and the CW group - tumour-bearing rats which received only a 0.9% NaCl solution. The effect of Aloe vera and honey against tumour growth was observed through a decrease in relative weight (%) and Ki67-LI in tumours from the WA group compared with those from the CW group. The Bax/Bcl-2 ratio increased in tumours from the WA group at all tested timepoints. These data suggest Aloe vera and honey can modulate tumour growth by reducing cell proliferation and increasing apoptosis susceptibility. PMID:20839215

  13. Surgical implications of tumour immunology.

    PubMed Central

    Somers, S. S.

    1996-01-01

    The presence of immune infiltration of tumour deposits and the existence of effective in vitro anti-tumour immune responses would suggest the possibility of therapeutic manipulation against tumour cells. However, clinical immunotherapy has shown little promise as a cancer treatment. Numerous explanations for this inefficacy have been proposed, one of which involves the elaboration of immunosuppressive moieties from tumour cells. The results of studies presented below show that serum from patients with gastrointestinal and other tumours have immunosuppressive influences on normal lymphocytes. The degree of this in vitro inhibition is related to tumour 'bulk' and may reflect a systemic immunosuppressive influence of the tumour. Isolation and culture of lymphocytes from gastrointestinal tumour deposits demonstrated that these immune cells are functionally inert, suggesting the existence of an immunosuppressive tumour microenvironment. The isolation and partial purification of an immunosuppressive moiety from conditioned culture medium of a variety of human tumour cell lines further supports the hypothesis of tumour-mediated immunosuppression. A number of protein tumour cell products have been described with potent immunosuppressive properties. These include transforming growth factor-beta, interleukin-10, and the retroviral envelope protein p15E. The surgical implications of the proposed tumour-host immune relationship includes the hypothesis that clinically apparent disease may not be amenable to immune attack owing to tumour-mediated immune suppression. The use of immunostimulatory strategies as adjuvant perioperative therapy would seem a more effective environment for the activation of antitumour immune responses in the surgical patient. PMID:8678441

  14. Tumours of the thymus

    PubMed Central

    Sellors, T. Holmes; Thackray, A. C.; Thomson, A. D.

    1967-01-01

    Eighty-eight cases of thymoma are discussed with the object of trying to co-ordinate the histological and clinical features. The pathological specimens were in all cases obtained at operation. The pathology classification introduced by Thomson and Thackray in 1957 has been found to correspond adequately with the clinical pattern. The most common groups of tumours are basically epithelial and can be separated into five or six subdivisions, each of which has a separate pattern of behaviour. Lymphoid and teratomatous tumours also occur, but there were only two examples in this series. Clinically, separation of patients who suffered from myasthenia (38) and those who did not (50) affords the first main grouping. The majority of patients who had myasthenia gravis had tumours classified as epidermoid (19) and lymphoepithelial (14), the former with a more malignant appearance and behaviour than the latter. Removal of the tumour with or without radiation gave considerable and sometimes complete relief from myasthenic symptoms. Non-myasthenic thymoma (50) was usually discovered as a result of pressure signs or in the course of routine radiography. Spindle or oval celled tumours followed a benign pattern whereas undifferentiated thymoma was in every sense malignant, as also were teratomatous growths. Granulomatous or Hodgkin-like thymomas were of special interest and had an unpredictable course, some patients surviving many years after what was regarded as inadequate treatment. The place of radiotherapy as a pre- or post-operative agent complementary to surgery is discussed. Images PMID:6033387

  15. Serially heterotransplanted human prostate tumours as an experimental model

    PubMed Central

    Lopez-Barcons, Lluis-A

    2010-01-01

    Abstract Preclinical research on prostate cancer (PC) therapies uses several models to represent the human disease accurately. A common model uses patient prostate tumour biopsies to develop a cell line by serially passaging and subsequent implantation, in immunodeficient mice. An alternative model is direct implantation of patient prostate tumour biopsies into immunodeficient mice, followed by serial passage in vivo. The purpose of this review is to compile data from the more than 30 years of human PC serial heterotransplantation research. Serially heterotransplanted tumours are characterized by evaluating the histopathology of the resulting heterotransplants, including cellular differentiation, karyotype, marker expression, hormone sensitivity, cellular proliferation, metastatic potential and stromal and vascular components. These data are compared with the initial patient tumour specimen and, depending on available information, the patient’s clinical outcome was compared with the heterotransplanted tumour. The heterotansplant model is a more accurate preclinical model than older generation serially passaged or genetic models to investigate current and newly developed androgen-deprivation agents, antitumour compounds, anti-angiogenic drugs and positron emission tomography radiotracers, as well as new therapeutic regimens for the treatment of PC. PMID:19874422

  16. Immunology of naturally transmissible tumours

    PubMed Central

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  17. Immunology of naturally transmissible tumours.

    PubMed

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  18. Parallel evolution of tumour subclones mimics diversity between tumours.

    PubMed

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome. PMID:23716380

  19. Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue

    PubMed Central

    Lilge, L; Portnoy, M; Wilson, B C

    2000-01-01

    The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET 2), and meta-tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer. © 2000 Cancer Research Campaign PMID:10993661

  20. Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue.

    PubMed

    Lilge, L; Portnoy, M; Wilson, B C

    2000-10-01

    The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET(2)), and meta -tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer. PMID:10993661

  1. Tumour Cell Heterogeneity

    PubMed Central

    Gay, Laura; Baker, Ann-Marie; Graham, Trevor A.

    2016-01-01

    The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment. PMID:26973786

  2. Direct evidence that hydralazine can induce hypoxia in both transplanted and spontaneous murine tumours.

    PubMed Central

    Horsman, M. R.; Nordsmark, M.; Høyer, M.; Overgaard, J.

    1995-01-01

    Hydralazine can substantially decrease blood flow and increase hypoxia in transplanted tumours. Previous indirect studies have suggested that hydralazine does not induce such effects in spontaneous tumours. We have now directly investigated the ability of hydralazine to increase hypoxia in both transplanted and spontaneous murine tumours by measuring tumour oxygen partial pressure (pO2) distributions using an Eppendorf oxygen electrode. Spontaneous tumours arose at different sites in CDF1 mice, while transplanted tumours were produced by implanting a C3H mouse mammary carcinoma on the backs of the same mouse strain. Measurements of pO2 were made in anaesthetised mice immediately before and 45 min after an intravenous injection of 5 mg kg-1 hydralazine. In the transplanted tumours hydralazine significantly decreased tumour oxygenation, such that the percentage of pO2 values < or = 5 mmHg increased from 45% to 87%, and median pO2 decreased from 5 to 3 mmHg. Similar significant changes were induced by hydralazine in the spontaneous tumours, the percentage of pO2 values < or = 5 mmHg increasing from 60% to 94% while the median pO2 values decreased from 8 to 2 mmHg. These results clearly show that there is no difference in the response of transplanted and spontaneous mouse tumours to hydralazine. PMID:8519662

  3. Fatty tumours of the uterus.

    PubMed Central

    Pounder, D J

    1982-01-01

    Uterine fatty tumours (UFT) are uncommon and have received little attention in the English literature. They have aroused interest as a consequence of occasional diagnostic confusion with sarcomas and the continuing unresolved dispute as to their histogenesis. Three cases of UFT are described and the pathological features of note discussed. The viewpoint that these tumours are hamartomas/choristomas is rejected. UFT most probably represent tumour metaplasia within a leiomyoma. There is no uniform accepted nomenclature for such tumours and it is suggested that they be designated "uterine fatty tumours" and subdivided into "lipoma" and "mixed lipoma/leiomyoma" (synonym lipoleiomyoma). Images PMID:7174848

  4. Tumour stroma-derived lipocalin-2 promotes breast cancer metastasis.

    PubMed

    Ören, Bilge; Urosevic, Jelena; Mertens, Christina; Mora, Javier; Guiu, Marc; Gomis, Roger R; Weigert, Andreas; Schmid, Tobias; Grein, Stephan; Brüne, Bernhard; Jung, Michaela

    2016-07-01

    Tumour cell-secreted factors skew infiltrating immune cells towards a tumour-supporting phenotype, expressing pro-tumourigenic mediators. However, the influence of lipocalin-2 (Lcn2) on the metastatic cascade in the tumour micro-environment is still not clearly defined. Here, we explored the role of stroma-derived, especially macrophage-released, Lcn2 in breast cancer progression. Knockdown studies and neutralizing antibody approaches showed that Lcn2 contributes to the early events of metastasis in vitro. The release of Lcn2 from macrophages induced an epithelial-mesenchymal transition programme in MCF-7 breast cancer cells and enhanced local migration as well as invasion into the extracellular matrix, using a three-dimensioanl (3D) spheroid model. Moreover, a global Lcn2 deficiency attenuated breast cancer metastasis in both the MMTV-PyMT breast cancer model and a xenograft model inoculating MCF-7 cells pretreated with supernatants from wild-type and Lcn2-knockdown macrophages. To dissect the role of stroma-derived Lcn2, we employed an orthotopic mammary tumour mouse model. Implantation of wild-type PyMT tumour cells into Lcn2-deficient mice left primary mammary tumour formation unaltered, but specifically reduced tumour cell dissemination into the lung. We conclude that stroma-secreted Lcn2 promotes metastasis in vitro and in vivo, thereby contributing to tumour progression. Our study highlights the tumourigenic potential of stroma-released Lcn2 and suggests Lcn2 as a putative therapeutic target. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27038000

  5. Glomus tumour of the stomach.

    PubMed

    Troller, Rebekka; Soll, Christopher; Breitenstein, Stefan

    2016-01-01

    Glomus tumours are benign tumours typically arising from the glomus bodies and primarily found under the fingernails or toenails. These rare neoplasms account for <2% of all soft tissue tumours and are generally not found in the gastrointestinal tract. We report a case of a 40-year-old man presenting with recurrent epigastric pain and pyrosis. Endoscopy revealed a solitary tumour in the antrum of the stomach. Fine-needle aspiration biopsy was suspicious for a gastrointestinal stroma tumour. After CT indicated the resectability of the tumour, showing neither lymphatic nor distant metastases, a laparoscopic-assisted gastric wedge resection was performed. Surprisingly, histology revealed a glomus tumour of the stomach. PMID:27343282

  6. Towards fluoroscopic respiratory gating for lung tumours without radiopaque markers

    NASA Astrophysics Data System (ADS)

    Berbeco, Ross I.; Mostafavi, Hassan; Sharp, Gregory C.; Jiang, Steve B.

    2005-10-01

    Due to the risk of pneumothorax, many clinicians are reluctant to implant radiopaque markers within patients' lungs for the purpose of radiographic or fluoroscopic tumour localization. We propose a method of gated therapy using fluoroscopic information without the implantation of radiopaque markers. The method presented here does not rely on any external motion signal either. Breathing phase information is found by analysing the fluoroscopic intensity fluctuations in the lung. As the lungs fill/empty, the radiological pathlength through them shortens/lengthens, giving brighter/darker fluoroscopic intensities. The phase information is combined with motion-enhanced template matching to turn the beam on when the tumour is in the desired location. A study based on patient data is presented to demonstrate the feasibility of this procedure. The resulting beam-on pattern is similar to that produced by an external gating system. The only discrepancies occur briefly and at the gate edges.

  7. Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster.

    PubMed Central

    Leunig, M.; Richert, C.; Gamarra, F.; Lumper, W.; Vogel, E.; Jocham, D.; Goetz, A. E.

    1993-01-01

    In this study the localisation of porphyrinoid photosensitizers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitizers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitizers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitizers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers. Images Figure 6 PMID

  8. Cochlear Implants

    MedlinePlus

    ... electrodes are inserted. The electronic device at the base of the electrode array is then placed under ... FDA approval for implants The Food and Drug Administration (FDA) regulates cochlear implant devices for both adults ...

  9. Goserelin Implant

    MedlinePlus

    Goserelin implant is used in combination with radiation therapy and other medications to treat localized prostate cancer and is ... treatment of abnormal bleeding of the uterus. Goserelin implant is in a class of medications called gonadotropin- ...

  10. Cochlear Implants

    MedlinePlus

    A cochlear implant is a small, complex electronic device that can help to provide a sense of sound. People who are ... of-hearing can get help from them. The implant consists of two parts. One part sits on ...

  11. Carmustine Implant

    MedlinePlus

    Carmustine implant is used along with surgery and sometimes radiation therapy to treat malignant glioma (a certain type of ... Carmustine implant comes as a small wafer that is placed in the brain by a doctor during surgery to ...

  12. Breast Implants

    MedlinePlus

    ... Updated Safety Information (Consumer Article) FDA Provides Updated Safety Data on Silicone Gel-Filled Breast Implants (Press Announcement) [ARCHIVED] Breast Implant Guidance for Industry (2006) Post Approval Studies Webpage Freedom of Information ...

  13. Cochlear implant

    MedlinePlus

    ... antenna. This part of the implant receives the sound, converts the sound into an electrical signal, and sends it to ... implants allow deaf people to receive and process sounds and speech. However, these devices do not restore ...

  14. Tumours of the kidney

    PubMed Central

    Nielsen, Svend W.; Mackey, L. J.; Misdorp, W.

    1976-01-01

    The most frequent renal tumours of animals are renal cell carcinoma and nephroblastoma. Renal cell carcinomas are seen mainly in dogs and cattle and nephroblastoma is encountered in pigs, puppies, and calves. Renal cell carcinomas are usually papillary in the dog. They show a marked propensity for vascular invasion, penetration of the posterior vena cava, and subsequent pulmonary metastasis. Nephroblastoma, which is morphologically identical to Wilms' tumour of children, is almost always a benign tumour in animals. It is one of the most frequent neoplasms of pigs, possibly owing to the fact that most pigs are slaughtered (and examined) when a few months old. Lymphosarcoma involving the kidney is particularly frequent in the cat, but is also seen in other species as part of a generalized disease. ImagesFig. 5,6Fig. 7Fig. 8Fig. 1,2Fig. 3,4Fig. 16,17,18,19Fig. 9,10Fig. 11Fig. 12Fig. 13Fig. 14,15 PMID:1086154

  15. Borderline ovarian tumours.

    PubMed

    Tropé, Claes Göran; Kaern, Janne; Davidson, Ben

    2012-06-01

    Borderline ovarian tumours account for 10-20% of all epithelial ovarian cancer. Historically, standard primary surgery has included borderline ovarian tumours, omentectomy, peritoneal washing and multiple biopsies. As one-third of borderline ovarian tumours are diagnosed in women under the age of 40 years, fertility-sparing treatment has been more frequently used in the past 10 years. Fertility drugs are well tolerated in women with infertility after fertility-sparing surgery. Careful selection of candidates is necessary. Laparoscopic techniques can be used, but should be reserved for oncologic surgeons. This conservative treatment increases the rate of recurrence, albeit with no effect on survival. The pregnancy rate is nearly 50%, and most are achieved spontaneously. These women should be closely followed up. The question is whether this is acceptable from a gynaecologic oncologic point of view. For this reason, we will discuss recently published studies and gynaecologic oncologic concerns about the mode of fertility-sparing surgery and its consequences. PMID:22321906

  16. Clinical features of gastroenteropancreatic tumours

    PubMed Central

    Czarnywojtek, Agata; Bączyk, Maciej; Ziemnicka, Katarzyna; Fischbach, Jakub; Wrotkowska, Elżbieta; Ruchała, Marek

    2015-01-01

    Gastroenteropancreatic (GEP) endocrine tumours (carcinoids and pancreatic islet cell tumours) are composed of multipotent neuroendocrine cells that exhibit a unique ability to produce, store, and secrete biologically active substances and cause distinct clinical syndromes. The classification of GEP tumours as functioning or non-functioning is based on the presence of symptoms that accompany these syndromes secondary to the secretion of hormones, neuropeptides and/or neurotransmitters (functioning tumours). Non-functioning tumours are considered to be neoplasms of neuroendocrine differentiation that are not associated with obvious symptoms attributed to the hypersecretion of metabolically active substances. However, a number of these tumours are either capable of producing low levels of such substances, which can be detected by immunohistochemistry but are insufficient to cause symptoms related to a clinical syndrome, or alternatively, they may secrete substances that are either metabolically inactive or inappropriately processed. In some cases, GEP tumours are not associated with the production of any hormone or neurotransmitter. Both functioning and non-functioning tumours can also produce symptoms due to mass effects compressing vital surrounding structures. Gastroenteropancreatic tumours are usually classified further according to the anatomic site of origin: foregut (including respiratory tract, thymus, stomach, duodenum, and pancreas), midgut (including small intestine, appendix, and right colon), and hindgut (including transverse colon, sigmoid, and rectum). Within these subgroups the biological and clinical characteristics of the tumours vary considerably, but this classification is still in use because a significant number of previous studies, mainly observational, have used it extensively. PMID:26516377

  17. Biophysical models of tumour growth

    NASA Astrophysics Data System (ADS)

    Tracqui, P.

    2009-05-01

    Tumour growth is a multifactorial process, which has stimulated in recent decades the development of numerous models trying to figure out the mechanisms controlling solid tumours morphogenesis. While the earliest models were focusing on cell proliferation kinetics, modulated by the availability of supplied nutrients, new modelling approaches emphasize the crucial role of several biophysical processes, including local matrix remodelling, active cell migration and traction, and reshaping of host tissue vasculature. After a brief presentation of this experimental background, this review will outline a number of representative models describing, at different scales, the growth of avascular and vascularized tumours. Special attention will be paid to the formulation of tumour-host tissue interactions that selectively drive changes in tumour size and morphology, and which are notably mediated by the mechanical status and elasticity of the tumour microenvironment. Emergence of invasive behaviour through growth instabilities at the tumour-host interface will be presented considering both reaction-diffusion and mechano-cellular models. In the latter part of the review, patient-oriented implications of tumour growth modelling are outlined in the context of brain tumours. Some conceptual views of the adaptive strategies and selective barriers that govern tumour evolution are presented in conclusion as potential guidelines for the development of future models.

  18. Maspin as a Tumour Suppressor in Salivary Gland Tumour

    PubMed Central

    Ashok, Nipun; Sheirawan, Mohammad Kinan; Altamimi, Mohammed Alsakran; Alenzi, Faris; Azzeghaiby, Saleh Nasser; Baroudi, Kusai; Nassani, Mohammad Zakaria

    2014-01-01

    Maspin is a protein that belongs to serin protease inhibitor (serpin) superfamily. The purpose of this study was to review the literature concerning the expression of maspin in salivary gland tumours. A literature search was done using MEDLINE, accessed via the National Library of Medicine PubMed interface. Statistical analysis was not done because only seven studies were available in literature, the collected data were different and the results could not be compared. Expression of maspin was down regulated in more aggressive salivary gland tumours. Maspin may function as a tumour suppressor in salivary gland tumours. PMID:25654053

  19. Stimulation of anti-tumour immunity in guinea-pigs by methanol extraction residue of BCG.

    PubMed Central

    Wainberg, M. A.; Deutsch, V.; Weiss, D. W.

    1976-01-01

    The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis. PMID:187207

  20. A New Model for Inducing Malignant Ovarian Tumours in Rats*

    PubMed Central

    Hilfrich, J.

    1973-01-01

    After the implantation of ovarian tissue into the spleen of gonadectomized female Sprague-Dawley rats (splenic ovary), luteomata and later benign granulosa or granulosa-theca cell tumours develop. Treatment of these rats with 7,12 dimethylbenz(a)anthracene (DMBA), given intravenously, 2 mg/kg body weight weekly, total dosage 40 mg/kg, immediately and especially 25 weeks after implantation of ovarian tissue into the spleen, led to malignant, partially metastasizing granulosa, and in one case theca cell tumours, 16-46 weeks after beginning the carcinogen treatment. No malignant neoplastic growth was seen when diethylnitrosamine (DEN), 20 mg/kg once weekly for life, was injected subcutaneously immediately or 25 weeks after implanting ovarian tissue. Since the normal, non-implanted rat ovary was not affected by DMBA treatment the malignant transformation of splenic ovaries in the respective experimental groups may be related to the increased stimulation by pituitary gonadotrophins and formation of luteomata or beginning granulosa and theca cell proliferations. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9 PMID:4353388

  1. Implantable Microimagers

    PubMed Central

    Ng, David C.; Tokuda, Takashi; Shiosaka, Sadao; Tano, Yasuo; Ohta, Jun

    2008-01-01

    Implantable devices such as cardiac pacemakers, drug-delivery systems, and defibrillators have had a tremendous impact on the quality of live for many disabled people. To date, many devices have been developed for implantation into various parts of the human body. In this paper, we focus on devices implanted in the head. In particular, we describe the technologies necessary to create implantable microimagers. Design, fabrication, and implementation issues are discussed vis-à-vis two examples of implantable microimagers; the retinal prosthesis and in vivo neuro-microimager. Testing of these devices in animals verify the use of the microimagers in the implanted state. We believe that further advancement of these devices will lead to the development of a new method for medical and scientific applications.

  2. High Productivity Implantation ''PARTIAL IMPLANT''

    SciTech Connect

    Hino, Masayoshi; Miyamoto, Naoki; Sakai, Shigeki; Matsumoto, Takao

    2008-11-03

    The patterned ion implantation 'PARTIAL IMPLANT' has been developed as a productivity improvement tool. The Partial Implant can form several different ion dose areas on the wafer surface by controlling the speed of wafer moving and the stepwise rotation of twist axis. The Partial Implant system contains two implant methods. One method is 'DIVIDE PARTIAL IMPLANT', that is aimed at reducing the consumption of the wafer. The Divide Partial Implant evenly divides dose area on one wafer surface into two or three different dose part. Any dose can be selected in each area. So the consumption of the wafer for experimental implantation can be reduced. The second method is 'RING PARTIAL IMPLANT' that is aimed at improving yield by correcting electrical characteristic of devices. The Ring Partial Implant can form concentric ion dose areas. The dose of wafer external area can be selected to be within plus or minus 30% of dose of wafer central area. So the electrical characteristic of devices can be corrected by controlling dose at edge side on the wafer.

  3. Metabolic reprogramming of the tumour microenvironment.

    PubMed

    Xing, Yazhi; Zhao, Shimin; Zhou, Binhua P; Mi, Jun

    2015-10-01

    Tumour cells, stromal cells and the stroma comprise the tumour microenvironment. The metabolism of both tumour cells and several types of tumour stromal cells, such as cancer-associated fibroblasts and tumour-associated macrophages, is reprogrammed. Current studies have found that stromal cells promote tumour progression and metastasis, through not only the paracrine secretion of cytokines or chemokines, but also intermediate metabolites. Here, we summarize the latest insights into the mechanism of metabolic reprogramming in cancer cells, cancer-associated fibroblasts and tumour-associated macrophages, and their potential roles in tumour progression and metastasis. PMID:26255648

  4. One very rare and one new tracheal tumour found by electron microscopy: glomus tumour and acinic cell tumour resembling carcinoid tumours by light microscopy.

    PubMed Central

    Heard, B E; Dewar, A; Firmin, R K; Lennox, S C

    1982-01-01

    Tracheal tumours were removed surgically from two patients and diagnosed as carcinoid tumours by routine light microscopy. At a later date, electron microscopy was performed on stored tumour tissue and no neurosecretory granules were found in either case. One showed features of a glomus tumour and the other of an acinic cell tumour. Only two glomus tumours appear to have been reported previously in the trachea, and no acinic cell tumours. Electron microscopy is thus sometimes of great assistance in diagnosing accurately unusual tumours of the lower respiratory tract. Images PMID:6281934

  5. Recurrent hyperphosphatemic tumoural calcinosis

    PubMed Central

    Amit, Sonal; Agarwal, Asha; Nigam, Anand; Rao, Yashwant Kumar

    2012-01-01

    Tumoural calcinosis (TC) is a benign gradually developing disorder that can occur in a variety of clinical settings, characterised by subcutaneous deposition of calcium phosphate with or without giant cell reaction. We describe a case of 11-year-old girl presenting with recurrent hard swellings in the vicinity of shoulder and hip joints associated with elevated serum phosphate and normal serum calcium levels. TC has been mainly reported from Africa, with very few cases reported from India. After the diagnosis of hyperphosphatemic TC was established, the patient was treated with oral sevelamer and is under constant follow-up to detect recurrence, if any. The present case highlights the fact that although an uncommon lesion, TC must be considered in the differential diagnosis of subcutaneous hard lump in the vicinity of a joint. PMID:23010461

  6. [Implant allergies].

    PubMed

    Thomas, P; Thomsen, M

    2010-03-01

    An increasing number of patients receive and benefit from osteosynthesis materials or artificial joint replacement. The most common complications are mechanical problems or infection. Metals like nickel, chromium and cobalt as well as bone cement components like acrylates and gentamicin are potential contact allergens which can cause intolerance reactions to implants. Eczema, delayed wound/bone healing, recurrent effusions, pain and implant loosening all have been described as manifestation of implant allergy. In contrast to the high incidence of cutaneous metal allergy, allergies associated with implants are rare. Diagnosis of metal implant allergy is still difficult. Thus differential diagnoses--in particular infection--have to be excluded and a combined approach of allergologic diagnostics by patch test and histopathology of peri-implant tissue is recommended. It is still unknown which conditions induce allergic sensitization to implants or trigger peri-implant allergic reactions in the case of preexisting cutaneous metal allergy. Despite the risk of developing complications being unclear, titanium based osteosynthesis materials are recommended for metal allergic patients and the use of metal-metal couplings in arthroplasty is not recommended for such patients. If the regular CoCr-polyethylene articulation is employed, the patient should give informed written consent. PMID:20204719

  7. [Drug therapy for neuroendocrine tumours].

    PubMed

    Tóth, Miklós

    2013-09-29

    The author aims to review the established medical treatment options of neuroendocrine tumours, which have expanded greatly in recent years and present the most important aspects to be considered in planning patients' management. Medical treatment is usually considered in advanced stages of these tumours, as well as in cases of hormone overproduction. Somatostatin analogues have been known to be effective in alleviating hormone excess syndromes, especially carcinoid syndrome for the past 25 years. There is a convincing evidence that the somatostatin analogue octreotide is useful as an antitumor agent, at least in well-differentiated small intestinal neuroendocrine tumours and probably also in those of pancreatic origin. Interferons may be also used and the indications for their use may be almost the same. Optimal patient selection is mandatory for the use of cytotoxic chemotherapy. Streptozotocin- and, recently, temozolomide-based chemotherapies should be considered in progressive phases of well differentiated (G1/G2) pancreatic neuroendocrine tumours. A cisplatin-etoposide combination is the first choice for the treatment of G3 neuroendocrine carcinomas of any origin. Recently, the mammalian target of rapamycin inhibitor everolimus and the combined tyrosine kinase inhibitor sunitinib were registered for the treatment of G1/G2 pancreatic neuroendocrine tumours. The most recent drug treatment recommendations and therapeutic algorithms to improve systemic therapy in patients with neuroendocrine tumours are summarized and novel drug candidates with particular potential for future management of these tumours are outlined. PMID:24058101

  8. Tumours of bones and joints

    PubMed Central

    Misdorp, W.; Van Der Heul, R. O.

    1976-01-01

    Tumours of bones and joints are not infrequent in dogs but are rare in other domestic animals. In the dog, most bone tumours are malignant; osteosarcomas are by far the most frequently encountered tumours, especially in giant breeds and boxers. The following main categories of bone tumour are described: bone-forming, cartilage-forming, giant cell, marrow, vascular, miscellaneous, metastatic, unclassified, and tumour-like lesions. The tumours of joints and related structures are classified as synovial sarcomas, fibroxanthomas, and malignant giant cell tumour of soft tissues. ImagesFig. 21Fig. 22Fig. 23Fig. 24Fig. 17Fig. 18Fig. 19Fig. 20Fig. 29Fig. 30Fig. 31Fig. 32Fig. 33Fig. 34Fig. 35Fig. 36Fig. 25Fig. 26Fig. 27Fig. 28Fig. 1Fig. 2Fig. 3Fig. 4Fig. 37Fig. 38Fig. 39Fig. 40Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086157

  9. Tumours of the urinary bladder

    PubMed Central

    Pamukcu, A. M.

    1974-01-01

    Tumours of the urinary bladder are uncommon in all domestic animals except cattle in certain regions. Where cattle eat bracken (Pteridium aquilinum) there is a high incidence of these tumours. Epithelial tumours are the most frequently encountered neoplasms in cattle and in dogs—the two species most studied. They are described under the following names: papilloma, adenoma, transitional cell carcinoma (with variants), squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16 PMID:4371741

  10. Distribution of Photofrin between tumour cells and tumour associated macrophages.

    PubMed Central

    Korbelik, M.; Krosl, G.; Olive, P. L.; Chaplin, D. J.

    1991-01-01

    Photofrin levels in cells derived from SCCVII tumours, excised from mice that previously received the drug, were measured using a fluorescence activated cell sorter (FACS). Concomitantly, in the same cells the FACS was used to measure fluorescein isothiocyanate (FITC) fluorescence that originated from FITC-conjugated antimouse IgG added to the cell suspension before sorting. This later measurement enabled discrimination between IgG negative tumour malignant cells and IgG positive host cells (primarily macrophages). In addition, cellular Photofrin content in 'tumour' and 'host' cells sorted by FACS was determined by chemical extraction. The measurements were performed for the time intervals 1-96 h post Photofrin administration. The data showed consistently higher Photofrin levels in the 'host cells', i.e., tumour associated macrophages (TAM), than in 'tumour' cells. On a per cell basis, at any time point studied there was a minimum of 1.7 times more Photofrin in 'host' than in 'tumour cells', while at 4-12 h postadministration, ratios of up to 3.0 times were observed. This corresponds to ratio values greater than 9, when based on Photofrin content per micrograms cell protein. PMID:1832927

  11. Rewiring macrophages for anti-tumour immunity.

    PubMed

    Lee, Yunqin; Biswas, Subhra K

    2016-06-28

    Tumour-associated macrophages facilitate cancer progression, but whether they can be reprogrammed to elicit an anti-tumour response remains unclear. Deletion of the microRNA-processing enzyme Dicer is now shown to rewire macrophages to an anti-tumour mode, leading to an enhanced response to immunotherapy and inhibition of tumour progression. PMID:27350442

  12. Leydig cell tumours in childhood.

    PubMed

    Mengel, W; Knorr, D

    1983-01-01

    Two cases of Leydig cell tumours in childhood are presented. In one case, delayed diagnosis and operation led to pubertas praecox vera whereas in the other case normal growth and development occurred after early diagnosis and operation. PMID:6878724

  13. A rare benign ovarian tumour.

    PubMed

    Palmeiro, Marta Morna; Cunha, Teresa Margarida; Loureiro, Ana Luisa; Esteves, Gonçalo

    2016-01-01

    Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery. PMID:26933186

  14. Quantifying tumour heterogeneity with CT

    PubMed Central

    Miles, Kenneth A.

    2013-01-01

    Abstract Heterogeneity is a key feature of malignancy associated with adverse tumour biology. Quantifying heterogeneity could provide a useful non-invasive imaging biomarker. Heterogeneity on computed tomography (CT) can be quantified using texture analysis which extracts spatial information from CT images (unenhanced, contrast-enhanced and derived images such as CT perfusion) that may not be perceptible to the naked eye. The main components of texture analysis can be categorized into image transformation and quantification. Image transformation filters the conventional image into its basic components (spatial, frequency, etc.) to produce derived subimages. Texture quantification techniques include structural-, model- (fractal dimensions), statistical- and frequency-based methods. The underlying tumour biology that CT texture analysis may reflect includes (but is not limited to) tumour hypoxia and angiogenesis. Emerging studies show that CT texture analysis has the potential to be a useful adjunct in clinical oncologic imaging, providing important information about tumour characterization, prognosis and treatment prediction and response. PMID:23545171

  15. Multicellular Streaming in Solid Tumours

    NASA Astrophysics Data System (ADS)

    Kas, Josef

    As early as 400 BCE, the Roman medical encyclopaedist Celsus recognized that solid tumours are stiffer than surrounding tissue. However, cancer cell lines are softer, and softer cells facilitate invasion. This paradox raises several questions: Does softness emerge from adaptation to mechanical and chemical cues in the external microenvironment, or are soft cells already present inside a primary solid tumour? If the latter, how can a more rigid tissue contain more soft cells? Here we show that in primary tumour samples from patients with mammary and cervix carcinomas, cells do exhibit a broad distribution of rigidities, with a higher fraction of softer and more contractile cells compared to normal tissue. Mechanical modelling based on patient data reveals that, surprisingly, tumours with a significant fraction of very soft cells can still remain rigid. Moreover, in tissues with the observed distributions of cell stiffnesses, softer cells spontaneously self-organize into lines or streams, possibly facilitating cancer metastasis.

  16. Design of an improved surgical instrument for the removal of bladder tumours.

    PubMed

    Barnes, Spencer C; Shepherd, Duncan Et; Espino, Daniel M; Bryan, Rik T; Viney, Richard; Patel, Prashant

    2016-06-01

    The aim of this work was to design an add-on instrument that could potentially decrease the recurrence of non-muscle invasive bladder cancer. The current surgical approach permits spilled tumour cells to disseminate within the bladder, re-implant and cause tumour recurrence. An add-on instrument has been designed in the form of an opening cone intended to provide space for surgery and yet reduce tumour cell spillage and dissemination. A prototype was manufactured using the shape memory metal Nitinol which was activated using an electrical current to facilitate opening and supplemented with latex to provide a sealed environment. The prototype was tested in comparable surgical conditions utilising porcine bladder wall and blue dye to simulate tumour cells. It was demonstrated that the vast majority of dye was retained within the device, supporting the proposed aim. PMID:27075816

  17. Canine mammary tumours, an overview.

    PubMed

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  18. Imaging of skull base tumours.

    PubMed

    Thust, Stefanie Catherine; Yousry, Tarek

    2016-01-01

    The skull base is a highly complex and difficult to access anatomical region, which constitutes a relatively common site for neoplasms. Imaging plays a central role in establishing the differential diagnosis, to determine the anatomic tumour spread and for operative planning. All skull base imaging should be performed using thin-section multiplanar imaging, whereby CT and MRI can be considered complimentary. An interdisciplinary team approach is central to improve the outcome of these challenging tumours. PMID:27330416

  19. Goserelin Implant

    MedlinePlus

    ... which the type of tissue that lines the uterus [womb] grows in other areas of the body ... with the treatment of abnormal bleeding of the uterus. Goserelin implant is in a class of medications ...

  20. Ion Implantation

    NASA Astrophysics Data System (ADS)

    Langouche, G.; Yoshida, Y.

    In this tutorial we describe the basic principles of the ion implantation technique and we demonstrate that emission Mössbauer spectroscopy is an extremely powerful technique to investigate the atomic and electronic configuration around implanted atoms. The physics of dilute atoms in materials, the final lattice sites and their chemical state as well as diffusion phenomena can be studied. We focus on the latest developments of implantation Mössbauer spectroscopy, where three accelerator facilities, i.e., Hahn-Meitner Institute Berlin, ISOLDE-CERN and RIKEN, have intensively been used for materials research in in-beam and on-line Mössbauer experiments immediately after implantation of the nuclear probes.

  1. Dental Implants

    MedlinePlus Videos and Cool Tools

    ... facts so you can make an informed decision as to whether dental implants are right for your ... the jaw bone. It’s obviously not the same as the original connection , but functions just the same. ...

  2. Cochlear Implants

    MedlinePlus

    ... additional visits are needed for activating, adjusting, and programming the various electrodes that have been implanted. Also, ... to the center for checkups once the final programming is made to the speech processor. Both children ...

  3. Histrelin Implant

    MedlinePlus

    ... bone growth and development of sexual characteristics) in girls usually between 2 and 8 years of age ... MRI scans (radiology techniques designed to show the images of body structures) to find the implant when ...

  4. Anti-tumour activity of photodynamic therapy in combination with mitomycin C in nude mice with human colon adenocarcinoma.

    PubMed Central

    Ma, L. W.; Moan, J.; Steen, H. B.; Iani, V.

    1995-01-01

    The interaction of photodynamic therapy (PDT) and a chemotherapeutic drug, mitomycin C (MMC), was investigated using WiDr human colon adenocarcinoma tumours implanted on Balb/c athymic nude mice. The WiDr tumours were treated with PDT alone, MMC alone or with both. It was found that the combined treatment produced a greater retardation in the growth of the WiDr tumour than monotherapy with MMC or PDT. The synergistic effect was especially prominent when PDT was used in combination with a low dose of MMC (1 mg kg-1), since treatment of 1 mg kg-1 MMC alone had no effect on the tumour. The anti-tumour activity of PDT was found to be increased with MMC of 5 mg kg-1. The response of normal skin on mice feet to PDT slightly greater when PDT was combined with 5 mg kg-1 MMC than when PDT was applied alone, while no detectable additional effect on skin photosensitivity was observed when PDT was combined with 1 mg kg-1 MMC. An enhanced uptake of Photofrin in tumours was found 12 h and 24 h after administration of MMC. The effect of MMC on the cell cycle distribution of cell dissociated directly from the tumours was studied. The results suggest that the increased susceptibility to photoinactivation of Photofrin-sensitised tumours may be due to MMC-induced accumulation of the tumour cells in S-phase. PMID:7734319

  5. Physiological noise in murine solid tumours using T2*-weighted gradient-echo imaging: a marker of tumour acute hypoxia?

    NASA Astrophysics Data System (ADS)

    Baudelet, Christine; Ansiaux, Réginald; Jordan, Bénédicte F.; Havaux, Xavier; Macq, Benoit; Gallez, Bernard

    2004-08-01

    T2*-weighted gradient-echo magnetic resonance imaging (T2*-weighted GRE MRI) was used to investigate spontaneous fluctuations in tumour vasculature non-invasively. FSa fibrosarcomas, implanted intramuscularly (i.m.) in the legs of mice, were imaged at 4.7 T, over a 30 min or 1 h sampling period. On a voxel-by-voxel basis, time courses of signal intensity were analysed using a power spectrum density (PSD) analysis to isolate voxels for which signal changes did not originate from Gaussian white noise or linear drift. Under baseline conditions, the tumours exhibited spontaneous signal fluctuations showing spatial and temporal heterogeneity over the tumour. Statistically significant fluctuations occurred at frequencies ranging from 1 cycle/3 min to 1 cycle/h. The fluctuations were independent of the scanner instabilities. Two categories of signal fluctuations were reported: (i) true fluctuations (TFV), i.e., sequential signal increase and decrease, and (ii) profound drop in signal intensity with no apparent signal recovery (SDV). No temporal correlation between tumour and contralateral muscle fluctuations was observed. Furthermore, treatments aimed at decreasing perfusion-limited hypoxia, such as carbogen combined with nicotinamide and flunarizine, decreased the incidence of tumour T2*-weighted GRE fluctuations. We also tracked dynamic changes in T2* using multiple GRE imaging. Fluctuations of T2* were observed; however, fluctuation maps using PSD analysis could not be generated reliably. An echo-time dependency of the signal fluctuations was observed, which is typical to physiological noise. Finally, at the end of T2*-weighted GRE MRI acquisition, a dynamic contrast-enhanced MRI was performed to characterize the microenvironment in which tumour signal fluctuations occurred in terms of vessel functionality, vascularity and microvascular permeability. Our data showed that TFV were predominantly located in regions with functional vessels, whereas SDV occurred in regions

  6. Therapy-induced tumour secretomes promote resistance and tumour progression

    PubMed Central

    Obenauf, Anna C.; Zou, Yilong; Ji, Andrew L.; Vanharanta, Sakari; Shu, Weiping; Shi, Hubing; Kong, Xiangju; Bosenberg, Marcus C.; Wiesner, Thomas; Rosen, Neal; Lo, Roger S.; Massagué, Joan

    2015-01-01

    Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer1,2. Here we show that targeted therapy with BRAF, ALK, or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed melanoma and lung adenocarcinoma cells. This therapy-induced secretome (TIS) stimulates the outgrowth, dissemination, and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The vemurafenib reactive secretome in melanoma is driven by down-regulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of multiple signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and PI3K/AKT/mTOR pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant melanoma tumours, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy. PMID:25807485

  7. Tumours of the upper alimentary tract.

    PubMed

    Head, K W

    1976-01-01

    Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. PMID:1086147

  8. Oncoprotein stability after tumour resection.

    PubMed Central

    Ong, G.; Gullick, W.; Sikora, K.

    1990-01-01

    The means by which oncogenes and their products activate malignant transformation are currently under intense investigation. However, published papers on experiments using human tumour material do not always report in detail their methods of collection or storage of the specimens. In order to assess the stability of oncogene encoded proteins following collection or storage of human tumour biopsies, we have examined the rate of decay of the c-myc, neu and EGF-receptor proteins. Solid tumours, containing amplified copies of each oncogene, were established in nude mice and the stability of the oncogene protein in portions of each tumour, left in phosphate buffered saline at room temperature for varying time intervals, was examined by immunoblotting. Intact EGF-receptor and neu oncoproteins were present even after 24 h under these conditions while the c-myc protein was apparently rapidly degraded after 20 min. These data demonstrate that oncogene products decay at different rates after tumour resection and that collection of human biopsies should take this into account in order to provide the basis for consistent measurements of protein expression. Images Figure 1 Figure 2 Figure 3 PMID:2139576

  9. Pitfalls in colour photography of choroidal tumours

    PubMed Central

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  10. Canine Mammary Mixed Tumours: A Review

    PubMed Central

    Dantas Cassali, Geovanni; Cavalheiro Bertagnolli, Angélica; Ferreira, Enio; Araújo Damasceno, Karine; de Oliveira Gamba, Conrado; Bonolo de Campos, Cecília

    2012-01-01

    Mammary mixed tumours are the most frequent neoplasias in female dogs. In humans, mixed tumours are frequently found in the salivary glands and are known as pleomorphic adenomas. In addition to their histomorphologic similarities, mixed tumours and pleomorphic adenomas have the potential to become malignant and give rise to carcinomas in mixed tumours and carcinomas ex-pleomorphic adenoma, respectively. The factors associated with malignant transformation are still poorly known in the case of canine mixed tumours. However, this form of neoplasia tends to be associated with a better prognosis than other malignant histological types. This paper discusses the main features associated with female canine mammary mixed tumours. PMID:23193497

  11. Tumour-associated eosinophilia: a review.

    PubMed Central

    Lowe, D; Jorizzo, J; Hutt, M S

    1981-01-01

    In a recent study of cervical carcinoma, 13 cases with a marked eosinophil infiltrate around the tumour were found. The histological appearance of the tumours was distinctive and suggested a specific response, similar to the lymphocyte infiltration in medullary carcinoma of the breast and seminoma. A review of published reports shows that tumour-associated tissue eosinophilia (TATE) and tumour-associated blood eosinophilia (TABE) may be seen in tumours of different histological types from different anatomical sites, and may occur together or separately. Tumours with TATE alone appear to have a better prognosis that those without, while TABE is associated with tumor spread and a poor prognosis. Images PMID:7035499

  12. Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice

    PubMed Central

    Gil, M; Bieniasz, M; Seshadri, M; Fisher, D; Ciesielski, M J; Chen, Y; Pandey, R K; Kozbor, D

    2011-01-01

    Background: Therapies targeted towards the tumour vasculature can be exploited for the purpose of improving the systemic delivery of oncolytic viruses to tumours. Photodynamic therapy (PDT) is a clinically approved treatment for cancer that is known to induce potent effects on tumour vasculature. In this study, we examined the activity of PDT in combination with oncolytic vaccinia virus (OVV) against primary and metastatic tumours in mice. Methods: The effect of 2-[1-hexyloxyethyl-]-2-devinyl pyropheophorbide-a (HPPH)-sensitised-PDT on the efficacy of oncolytic virotherapy was investigated against subcutaneously implanted syngeneic murine NXS2 neuroblastoma and human FaDu head and neck squamous cell carcinoma xenografts in nude mice. Treatment efficacy was evaluated by monitoring tumour growth and survival. The effects of combination treatment on vascular function were examined using magnetic resonance imaging (MRI) and immunohistochemistry, whereas viral replication in tumour cells was analysed by a standard plaque assay. Normal tissue phototoxicity following PDT-OV treatment was studied using the mouse foot response assay. Results: Combination of PDT with OVV resulted in inhibition of primary and metastatic tumour growth compared with either monotherapy. PDT-induced vascular disruption resulted in higher intratumoural viral titres compared with the untreated tumours. Five days after delivery of OVV, there was a loss of blood flow to the interior of tumour that was associated with infiltration of neutrophils. Administration of OVV did not result in any additional photodynamic damage to normal mouse foot tissue. Conclusion: These results provide evidence into the usefulness of PDT as a means of enhancing intratumoural replication and therapeutic efficacy of OV. PMID:21989183

  13. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells

    PubMed Central

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi

    2015-01-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. PMID:25910782

  14. Anti-tumour activity of oncolytic Western Reserve vaccinia viruses in canine tumour cell lines, xenografts, and fresh tumour biopsies.

    PubMed

    Autio, K; Knuuttila, A; Kipar, A; Ahonen, M; Parviainen, S; Diaconu, I; Kanerva, A; Hakonen, T; Vähä-Koskela, M; Hemminki, A

    2014-10-10

    Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours. PMID:25302859

  15. Tailored nanoparticles for tumour therapy.

    PubMed

    Jiang, Pei-Shin; Drake, Philip; Cho, Hui-Ju; Kao, Chao-Hung; Lee, Kun-Feng; Kuo, Chien-Hung; Lin, Xi-Zhang; Lin, Yuh-Jiuan

    2012-06-01

    Gd doped iron-oxide nanoparticles were developed for use in tumour therapy via magnetic fluid hyperthermia (MFH). The effect of the Gd3+ dopant on the particle size and magnetic properties was investigated. The final particle composition varied from Gd0.01Fe2.99O4 to Gd0.04Fe2.96O4 as determined by Inductively coupled plasma atomic emission spectroscopy (ICP-AES). TEM image analysis showed the average magnetic core diameters to be 12 nm and 33 nm for the lowest and highest Gd levels respectively. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz had a maximum of 38Wg(-1) [Fe] for the Gd0.03Fe2.97O4 sample. This value is about 4 times higher than the reported SAR values for Fe3O4. The potential for in vivo tumour therapy was investigated using a mouse model. The mouse models treated with Gd0.02Fe2.98O4 displayed much slower tumour growth after the first treatment cycle, the tumour had increased its mass by 25% after 7 days post treatment compared to a 79% mass increase over the same period for those models treated with standard iron-oxide or saline solution. After a second treatment cycle the mouse treated with Gd0.02Fe2.98O4 showed complete tumour regression with no tumour found for at least 5 days post treatment. PMID:22905580

  16. A rare urinary bladder tumour

    PubMed Central

    Haddad-Lacle, Judella Edwina Maria; Haddad, Charles Joseph; Villas, Bruce

    2014-01-01

    This case report describes a 54-year-old man who presented to his primary care physician with low back pain. During his workup, an incidental finding of a bladder mass was diagnosed. He underwent transurethral resection of the bladder tumour and the resulting pathology was consistent with extra nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Presentation of MALT lymphoma in the urinary bladder is rare. This malignancy is more commonly found in the stomach. The prognosis for this rare tumour is excellent. Our patient showed no sign of recurrence with transurethral excision and radiation alone. PMID:24835803

  17. Brown tumour of the jaw

    PubMed Central

    Nair, Preeti P; Gharote, Harshkant P; Thomas, Shaji; R, Guruprasad; Singh, Neha

    2011-01-01

    Brown tumours are classic bony lesions that arise as a result of the effect of parathyroid hormone on bone tissue in some patients with hyperparathyroidism. They are erosive bony lesions caused by rapid osteolysis and peritrabecular fibrosis, resulting in a local destructive phenomenon. Facial skeleton is involved in about 2% of all cases of which the mandible is frequently affected. A 35-year-old female who was diagnosed with osteomalacia and brown tumour in posterior mandible as the sign of secondary hyperparathyroidism secondary to vitamin D deficiency is presented. PMID:22669885

  18. Cochlear Implants

    MedlinePlus

    ... outside of the body, behind the ear. A second part is surgically placed under the skin. An implant does not restore normal hearing. It can help a person understand speech. Children and adults can benefit from them. National Institute on Deafness and Other Communication Disorders

  19. Cochlear implant

    MedlinePlus

    ... are sent along the auditory nerve to the brain. A deaf person does not have a functioning inner ear. A cochlear implant tries to replace the function of the inner ear by ... signals to the brain. Sound is picked up by a microphone worn ...

  20. Interforaminal implant placement in oral cancer patients: during ablative surgery or delayed? A 5-year retrospective study.

    PubMed

    Mizbah, K; Dings, J P; Kaanders, J H A M; van den Hoogen, F J A; Koole, R; Meijer, G J; Merkx, M A W

    2013-05-01

    In a retrospective study, two mandibular prosthetic rehabilitation strategies supported by implants in oral cancer patients were evaluated: implants placed in the non-resected edentulous symphyseal area during ablative surgery (DAS implants); or at a later stage (postponed (P) implants). Medical files of patients from two head-neck oncology groups from 2000 to 2005 were screened for study inclusion. DAS protocol was used in one group and P protocol in the other. After a 5 year follow-up of 261 edentulous patients with oral cancer in the second group, P implants were placed in 27 patients to support an overdenture. Of the 249 edentulous patients in the first group, 82 patients were given an implant supported overdenture using the DAS implant protocol. Regarding implant loss, no statistically significant differences were seen between the DAS and P implants. In the DAS group, more patients benefited from an implant-supported lower overdenture (39 versus 11%, respectively), and they received their overdenture on average 20.0 months sooner (sd=11.01, p<0.001) after ablative surgery. 17.1% of DAS implants and 4.6% of P implants were never loaded due to tumour and patient related factors including unfavourable implant soft tissue, tumour recurrence near the implant, or radiotherapy induced trismus. PMID:23102901

  1. Tumours of the soft (mesenchymal) tissues.

    PubMed

    Weiss, E

    1974-01-01

    This is a classification of tumours of fibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours of fibrous tissue are divided into fibroma, fibrosarcoma (including "canine haemangiopericytoma"), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tumours is described and illustrated with photographs. PMID:4371740

  2. The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models

    PubMed Central

    Hussain, Nosheen; Connah, David; Ugail, Hassan; Cooper, Patricia A.; Falconer, Robert A.; Patterson, Laurence H.; Shnyder, Steven D.

    2016-01-01

    Non-invasive methods to monitor tumour growth are an important goal in cancer drug development. Thermographic imaging systems offer potential in this area, since a change in temperature is known to be induced due to changes within the tumour microenvironment. This study demonstrates that this imaging modality can be applied to a broad range of tumour xenografts and also, for the first time, the methodology’s suitability to assess anti-cancer agent efficacy. Mice bearing subcutaneously implanted H460 lung cancer xenografts were treated with a novel vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects on tumour temperature were assessed using thermographic imaging over the first 6 hours post-administration and subsequently a further 7 days. For ICT-2552 a significant initial temperature drop was observed, whilst for both agents a significant temperature drop was seen compared to controls over the longer time period. Thus thermographic imaging can detect functional differences (manifesting as temperature reductions) in the tumour response to these anti-cancer agents compared to controls. Importantly, these effects can be detected in the first few hours following treatment and therefore the tumour is observable non-invasively. As discussed, this technique will have considerable 3Rs benefits in terms of reduction and refinement of animal use. PMID:27491535

  3. The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models.

    PubMed

    Hussain, Nosheen; Connah, David; Ugail, Hassan; Cooper, Patricia A; Falconer, Robert A; Patterson, Laurence H; Shnyder, Steven D

    2016-01-01

    Non-invasive methods to monitor tumour growth are an important goal in cancer drug development. Thermographic imaging systems offer potential in this area, since a change in temperature is known to be induced due to changes within the tumour microenvironment. This study demonstrates that this imaging modality can be applied to a broad range of tumour xenografts and also, for the first time, the methodology's suitability to assess anti-cancer agent efficacy. Mice bearing subcutaneously implanted H460 lung cancer xenografts were treated with a novel vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects on tumour temperature were assessed using thermographic imaging over the first 6 hours post-administration and subsequently a further 7 days. For ICT-2552 a significant initial temperature drop was observed, whilst for both agents a significant temperature drop was seen compared to controls over the longer time period. Thus thermographic imaging can detect functional differences (manifesting as temperature reductions) in the tumour response to these anti-cancer agents compared to controls. Importantly, these effects can be detected in the first few hours following treatment and therefore the tumour is observable non-invasively. As discussed, this technique will have considerable 3Rs benefits in terms of reduction and refinement of animal use. PMID:27491535

  4. Goshajinkigan reduces oxaliplatin-induced peripheral neuropathy without affecting anti-tumour efficacy in rodents.

    PubMed

    Ushio, Soichiro; Egashira, Nobuaki; Sada, Hikaru; Kawashiri, Takehiro; Shirahama, Masafumi; Masuguchi, Ken; Oishi, Ryozo

    2012-06-01

    Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Goshajinkigan (GJG) is a Kampo medicine that is used for the treatments of several neurological symptoms including pain and numbness. More recently, GJG has been reported to prevent the oxaliplatin-induced peripheral neuropathy in clinical studies. No experimental study, however, has been conducted to date to determine the effect of GJG on pain behaviour in a rat model of oxaliplatin-induced neuropathy. Moreover, the impact on the anti-tumour effect of oxaliplatin remains unknown. In the present study, we examined the effects of GJG on the peripheral neuropathy and anti-tumour activity of oxaliplatin in rodents. Repeated administration of oxaliplatin caused cold hyperalgesia from days 3 to 37 and mechanical allodynia from days 21 to 28. Repeated administration of GJG prevented the oxaliplatin-induced cold hyperalgesia but not mechanical allodynia and axonal degeneration in rat sciatic nerve. Single administration of GJG reduced both cold hyperalgesia and mechanical allodynia after the development of neuropathy. In addition, GJG did not affect the anti-tumour effect of oxaliplatin in the tumour cells or tumour cells-implanted mice. These results suggest that GJG relieves the oxaliplatin-induced cold hyperalgesia and mechanical allodynia without affecting anti-tumour activity of oxaliplatin, and, therefore, may be useful for the oxaliplatin-induced neuropathy in clinical practice. PMID:21907570

  5. Brain tumour mortality in immigrants.

    PubMed

    Neutel, C I; Quinn, A; Brancker, A

    1989-03-01

    All Canadian deaths due to malignant brain tumour for the years 1970-73 were identified and analysed for country of birth. The years 1970-73 were chosen since in later years country of birth was no longer available for each death. The brain tumour population consisted of 1551 male and 1058 female deaths and matched controls were chosen from deaths due to other causes. Americans who died of brain tumour in Canada had a standardized mortality ratio (SMR) of 1.0 compared to their fellow Americans in the USA. Italian, German, Dutch and British immigrants had SMR between 1.5 and 2.6 compared to rates in their home countries and between 1.24 and 2.09 when compared to Canadian rates. A series of graphs shows the increased risk for male immigrants quite dramatically, and indicates that for females the increases were less pronounced. Further analysis showed that the excess risk is confined to those who were born in Western Europe while their Canadian-born children experienced the same rates as all Canadians. Based on the limited information available, occupation could not be shown to play a role in establishing risk. An attempt was made to pinpoint the years of immigration which showed the greatest risk. It is concluded that the determination of risk of brain tumour has a strong environmental component. The possibilities for identification of this component are discussed. PMID:2722385

  6. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  7. Interferon regulatory factor-8 modulates the development of tumour-induced CD11b+Gr-1+ myeloid cells.

    PubMed

    Stewart, Trina J; Greeneltch, Kristy M; Reid, Julia E; Liewehr, David J; Steinberg, Seth M; Liu, Kebin; Abrams, Scott I

    2009-09-01

    Tumour-induced myeloid-derived suppressor cells (MDSC) promote immune suppression and mediate tumour progression. However, the molecular basis for the generation of MDSC, which in mice co-express the CD11b(+) and Gr-1(+) cell surface markers remains unclear. Because CD11b(+)Gr-1(+) cells expand during progressive tumour growth, this suggests that tumour-induced events alter signalling pathways that affect normal myeloid cell development. Interferon regulatory factor-8 (IRF-8), a member of the IFN-gamma regulatory factor family, is essential for normal myelopoiesis. We therefore examined whether IRF-8 modulated tumour-induced CD11b(+)Gr-1(+) cell development or accumulation using both implantable (4T1) and transgenic (MMTV-PyMT) mouse models of mammary tumour growth. In the 4T1 model, both splenic and bone marrow-derived CD11b(+)Gr-1(+) cells of tumour-bearing mice displayed a marked reduction in IRF-8 expression compared to control populations. A causal link between IRF-8 expression and the emergence of tumour-induced CD11b(+)Gr-1(+) cells was explored in vivo using a double transgenic (dTg) mouse model designed to express transgenes for both IRF-8 and mammary carcinoma development. Despite the fact that tumour growth was unaffected, splenomegaly, as well as the frequencies and absolute numbers of CD11b(+)Gr-1(+) cells were significantly lower in dTg mice when compared with single transgenic tumour-bearing mice. Overall, these data reveal that IRF-8 plays an important role in tumour-induced development and/or accumulation of CD11b(+)Gr-1(+) cells, and establishes a molecular basis for the potential manipulation of these myeloid populations for cancer therapy. PMID:20196788

  8. Tumour vasculature--a potential therapeutic target.

    PubMed Central

    Baillie, C. T.; Winslet, M. C.; Bradley, N. J.

    1995-01-01

    The tumour vasculature is vital for the establishment, growth and metastasis of solid tumours. Its physiological properties limit the effectiveness of conventional anti-cancer strategies. Therapeutic approaches directed at the tumour vasculature are reviewed, suggesting the potential of anti-angiogenesis and the targeting of vascular proliferation antigens as cancer treatments. PMID:7543770

  9. Titanium wire implants with nanotube arrays: A study model for localized cancer treatment.

    PubMed

    Kaur, Gagandeep; Willsmore, Tamsyn; Gulati, Karan; Zinonos, Irene; Wang, Ye; Kurian, Mima; Hay, Shelley; Losic, Dusan; Evdokiou, Andreas

    2016-09-01

    Adverse complications associated with systemic administration of anti-cancer drugs are a major problem in cancer therapy in current clinical practice. To increase effectiveness and reduce side effects, localized drug delivery to tumour sites requiring therapy is essential. Direct delivery of potent anti-cancer drugs locally to the cancer site based on nanotechnology has been recognised as a promising alternative approach. Previously, we reported the design and fabrication of nano-engineered 3D titanium wire based implants with titania (TiO2) nanotube arrays (Ti-TNTs) for applications such as bone integration by using in-vitro culture systems. The aim of present study is to demonstrate the feasibility of using such Ti-TNTs loaded with anti-cancer agent for localized cancer therapy using pre-clinical cancer models and to test local drug delivery efficiency and anti-tumour efficacy within the tumour environment. TNF-related apoptosis-inducing ligand (TRAIL) which has proven anti-cancer properties was selected as the model drug for therapeutic delivery by Ti-TNTs. Our in-vitro 2D and 3D cell culture studies demonstrated a significant decrease in breast cancer cell viability upon incubation with TRAIL loaded Ti-TNT implants (TRAIL-TNTs). Subcutaneous tumour xenografts were established to test TRAIL-TNTs implant performance in the tumour environment by monitoring the changes in tumour burden over a selected time course. TRAIL-TNTs showed a significant regression in tumour burden within the first three days of implant insertion at the tumour site. Based on current experimental findings these Ti-TNTs wire implants have shown promising capacity to load and deliver anti-cancer agents maintaining their efficacy for cancer treatment. PMID:27289379

  10. Divergent effects of flavone acetic acid on established versus developing tumour blood flow.

    PubMed Central

    Mahadevan, V.; Hart, I. R.

    1991-01-01

    Flavone Acetic Acid (FAA) exerts much of its effect by reducing tumour blood flow. Previous studies on FAA-induced changes in blood flow have used established tumours with a functional microvasculature. Using radioactive Xenon(133Xe) clearance to monitor local blood flow we show that the effects of FAA are dependent on the presence of this functional microvasculature with no evidence that FAA inhibits the actual development of tumour microcirculation. Thus, administration of multiple doses of FAA around the time of tumour cell injection failed to diminish t1/2 values of 133Xe (e.g. t1/2 16 min for FAA vs 14 min for saline controls at 10 days) or to affect tumour volumes (5.55 +/- 0.06 cm3 in FAA-treated animals vs 5.7 +/- 1.3 cm3 in controls at 25 days). In marked contrast a single dose of FAA (200 mg kg-1 body weight) 2 weeks after tumour cell injection dramatically extended t1/2 times (47 min for FAA vs 7 min for controls; P less than 0.001) and significantly reduced tumour burden. This effect is specific for tumour microvasculature and is not directed simply at new vessels since a similar treatment of animals with implanted-sponge-induced granulation tissue had no effect on t1/2 times (6.8 +/- 1.1 min for FAA at 200 mg kg-1 vs 7.2 +/- 1.0 min for saline-treated controls. PMID:1712621

  11. Arteriolar oxygenation in tumour and subcutaneous arterioles: effects of inspired air oxygen content.

    PubMed Central

    Dewhirst, M. W.; Ong, E. T.; Rosner, G. L.; Rehmus, S. W.; Shan, S.; Braun, R. D.; Brizel, D. M.; Secomb, T. W.

    1996-01-01

    Carbogen is thought to be more effective than normobaric oxygen in reducing tumour hypoxia because it may reduce hyperoxic vasoconstriction. In this study, tumour and normal arteriolar diameters were measured simultaneously with perivascular pO2 during air breathing followed by either carbogen or 100% oxygen to determine whether the action of carbogen is the result of alterations in feeding vessel diameter. Fischer-344 rats bearing dorsal flap window chambers, with or without implanted R3230AC tumours, were the experimental subjects. Arteriolar diameters were measured using optical techniques and perivascular pO2 was measured using recessed-tip electrodes (3-6 microns tip diameter). Baseline arteriolar pO2 averaged 30-50% of blood gas pO2 (mean = 97 mmHg). Both hyperoxic gases increased blood gas pO2 by 4-to 5-fold, but relative improvements in arteriolar pO2 were < or = 2.5 for all arterioles studied. This means that these normobaric high O2 gases are not very efficient in increasing O2 delivery to tumours. In addition, improvements in tumour arteriolar pO2 were transient for both hyperoxic gases. Oxygen and carbogen caused no change and mild vasodilatory responses in tumour arterioles, respectively. Normal arterioles on the other hand, tended toward vasoconstriction by carbogen breathing. Peri-arteriolar pO2 in tumours increased within the first 5 min of breathing either hyperoxic gas, followed by a decline back toward values seen with air-breathing. These results suggest that temporal changes in tumour oxygenation after exposure to carbogen or O2 may not be due to changes in perfusion. Other factors, such as changes in O2 consumption rate may be involved. PMID:8763889

  12. The contribution of lactic acid to acidification of tumours: studies of variant cells lacking lactate dehydrogenase.

    PubMed Central

    Yamagata, M.; Hasuda, K.; Stamato, T.; Tannock, I. F.

    1998-01-01

    Solid tumours develop an acidic extracellular environment with high concentration of lactic acid, and lactic acid produced by glycolysis has been assumed to be the major cause of tumour acidity. Experiments using lactate dehydrogenase (LDH)-deficient ras-transfected Chinese hamster ovarian cells have been undertaken to address directly the hypothesis that lactic acid production is responsible for tumour acidification. The variant cells produce negligible quantities of lactic acid and consume minimal amounts of glucose compared with parental cells. Lactate-producing parental cells acidified lightly-buffered medium but variant cells did not. Tumours derived from parental and variant cells implanted into nude mice were found to have mean values of extracellular pH (pHe) of 7.03 +/- 0.03 and 7.03 +/- 0.05, respectively, both of which were significantly lower than that of normal muscle (pHe = 7.43 +/- 0.03; P < 0.001). Lactic acid concentration in variant tumours (450 +/- 90 microg g(-1) wet weight) was much lower than that in parental tumours (1880 +/- 140 microg/g(-1)) and similar to that in serum (400 +/- 35 microg/g(-1)). These data show discordance between mean levels of pHe and lactate content in tumours; the results support those of Newell et al (1993) and suggest that the production of lactic acid via glycolysis causes acidification of culture medium, but is not the only mechanism, and is probably not the major mechanism responsible for the development of an acidic environment within solid tumours. PMID:9667639

  13. Animal models of tumour-associated epilepsy.

    PubMed

    Kirschstein, Timo; Köhling, Rüdiger

    2016-02-15

    Brain tumours cause a sizeable proportion of epilepsies in adulthood, and actually can be etiologically responsible also for childhood epilepsies. Conversely, seizures are often first clinical signs of a brain tumour. Nevertheless, several issues of brain-tumour associated seizures and epilepsies are far from understood, or clarified regarding clinical consensus. These include both the specific mechanisms of epileptogenesis related to different tumour types, the possible relationship between malignancy and seizure emergence, the interaction between tumour mass and surrounding neuronal networks, and - not least - the best treatment options depending on different tumour types. To investigate these issues, experimental models of tumour-induced epilepsies are necessary. This review concentrates on the description of currently used models, focusing on methodological aspects. It highlights advantages and shortcomings of these models, and identifies future experimental challenges. PMID:26092434

  14. Haemangioleiomyomatous tumour of the lung.

    PubMed Central

    Soorae, A S; Bharucha, H

    1980-01-01

    A case of haemangioleiomyomatous tumour of the lung, occurring as a peripheral, solitary nodule in an asymptomatic 54-year-old man is presented. The tumour was well-demarcated and microscopically it was characterised by the presence of vascular spaces with endothelial, pericytic, and, predominantly, smooth muscle proliferation. Islands of cartilage and slit-like spaces lined by bronchial epithelium make this a hamartomatous lesion of a quite distinctive and unusual variety, which does not fit any of the well-recognised patterns of hamartomas previously described. The long-term prognosis after limited excision is considered to be favourable. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7358861

  15. Hypoxia-mediated tumour targeting.

    PubMed

    Binley, K; Askham, Z; Martin, L; Spearman, H; Day, D; Kingsman, S; Naylor, S

    2003-04-01

    Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter showed limited activity in the liver or spleen such that expression was 1000-fold lower than that driven by the strong CMV/IE promoter. However, in the context of the tumour microenvironment, the OBHRE promoter achieved expression levels comparable to that of the CMV/IE promoter. Next, we showed that an adenovirus expressing the human cytochrome P450 (CYP2B6) regulated by the OBHRE promoter delays tumour growth in response to the prodrug cyclophosphamide (CPA). Finally, we exploited the hepatotropism of adenovirus to investigate whether the OBHRE promoter could mitigate the hepatotoxicity of a recombinant adenovirus expressing thymidine kinase (TK) in the context of the prodrug ganciclovir (GCV). High-dose Ad.CMVTK/GCV treatment caused significant liver necrosis whereas the same dose of Ad.HRETK was well tolerated. These in vivo data demonstrate that hypoxia-targeted gene expression via the OBHRE promoter can be used to increase the therapeutic window of cytotoxic cancer gene therapy. PMID:12646859

  16. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours

    PubMed Central

    Braekeveldt, Noémie; Wigerup, Caroline; Gisselsson, David; Mohlin, Sofie; Merselius, My; Beckman, Siv; Jonson, Tord; Börjesson, Anna; Backman, Torbjörn; Tadeo, Irene; Berbegall, Ana P; Öra, Ingrid; Navarro, Samuel; Noguera, Rosa; Påhlman, Sven; Bexell, Daniel

    2015-01-01

    Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose–positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma. What's new? Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease have a poor outcome. Here, the authors established neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high-risk neuroblastoma into immunodeficient mice

  17. Fertility sparing treatment in borderline ovarian tumours

    PubMed Central

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  18. Fertility sparing treatment in borderline ovarian tumours.

    PubMed

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10-15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  19. Tumours of the liver and biliary system

    PubMed Central

    Ponomarkov, V.; Mackey, L. J.

    1976-01-01

    In this histological classification of liver and gall bladder tumours the tumour types largely correspond to those found in man. The most common tumours in this group are liver cell adenoma, hepatocellular carcinoma, and cholangiocarcinoma. ImagesFig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 1Fig. 2Fig. 3Fig. 4Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086149

  20. Malignant Leydig cell tumour of the testis.

    PubMed

    Powari, Manish; Kakkar, Nandita; Singh, S K; Rai, R S; Jogai, Sanjay

    2002-01-01

    A case of malignant Leydig cell tumour is presented. It is a rare primary malignant tumour of the testis and occurs exclusively in adults. The present case is of interest because it occurred at the young age of 25 years which is rare. Histologically it showed almost all features which suggest malignancy and also had metastases to the lungs and liver. The clinical details and pathology of this tumour are discussed. PMID:11803271

  1. Tumours of the upper alimentary tract

    PubMed Central

    Head, K. W.

    1976-01-01

    Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. ImagesFig. 6Fig. 7Fig. 8Fig. 9Fig. 34Fig. 35Fig. 36Fig. 37Fig. 2Fig. 3Fig. 4Fig. 5Fig. 22Fig. 23Fig. 24Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 14Fig. 15Fig. 16Fig. 17Fig. 30Fig. 31Fig. 32Fig. 33Fig. 18Fig. 19Fig. 20Fig. 21Fig. 10Fig. 11Fig. 12Fig. 13Fig. 1 PMID:1086147

  2. Tumour angiogenesis-Origin of blood vessels.

    PubMed

    Krishna Priya, S; Nagare, R P; Sneha, V S; Sidhanth, C; Bindhya, S; Manasa, P; Ganesan, T S

    2016-08-15

    The conventional view of tumour vascularization is that tumours acquire their blood supply from neighbouring normal stroma. Additional methods of tumour vascularization such as intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option and vasculogenesis have been demonstrated to occur. However, the origin of the endothelial cells and pericytes in the tumour vasculature is not fully understood. Their origin from malignant cells has been shown indirectly in lymphoma and neuroblastoma by immuno-FISH experiments. It is now evident that tumours arise from a small population of cells called cancer stem cells (CSCs) or tumour initiating cells. Recent data suggest that a proportion of tumour endothelial cells arise from cancer stem cells in glioblastoma. This was demonstrated both in vitro and in vivo. The analysis of chromosomal abnormalities in endothelial cells showed identical genetic changes to those identified in tumour cells. However, another report contradicted these results from the earlier studies in glioblastoma and had shown that CSCs give rise to pericytes and not endothelial cells. The main thrust of this review is the critical analysis of the conflicting data from different studies and the remaining questions in this field of research. The mechanism by which this phenomenon occurs is also discussed in detail. The transdifferentiation of CSCs to endothelial cells/pericytes has many implications in the progression and metastasis of the tumours and hence it would be a novel target for antiangiogenic therapy. PMID:26934471

  3. Tumour promotion versus tumour suppression in chronic hepatic iron overload.

    PubMed

    Bloomer, Steven A; Brown, Kyle E

    2015-06-01

    Although iron-catalysed oxidative damage is presumed to be a major mechanism of injury leading to cirrhosis and hepatocellular carcinoma in hemochromatosis, these events have been difficult to recapitulate in an animal model. In this study, we evaluated regulators of hepatocarcinogenesis in a rodent model of chronic iron overload. Sprague-Dawley rats were iron loaded with iron dextran over 6 months. Livers were harvested and analysed for markers of oxidative stress, as well as the following proteins: p53, murine double minute 2, the Shc proteins p66, p52, p46; β-catenin, CHOP, C/EBPα and Yes-associated protein. In this model, iron loading is associated with hepatocyte proliferation, and indices of oxidative damage are mildly increased in tandem with augmented antioxidant defenses. Alterations potentially favouring carcinogenesis included a modest but significant decrease in p53 levels and increases in p52, p46 and β-catenin levels compared with control livers. Countering these factors, the iron-loaded livers demonstrated a significant decrease in CHOP, which has recently been implicated in the development of hepatocellular carcinoma, as well as a reciprocal increase in C/EBPα and decrease in Yes-associated protein. Our results suggest that chronic iron overload elicits both tumour suppressive as well as tumour-promoting mechanisms in rodent liver. PMID:26059599

  4. [Pancreatic tumour in a child].

    PubMed

    Schouenborg Schultz, Thea; Thyssen Vestergaard, Esben

    2014-07-28

    Abdominal pain is a common symptom in children and recurrent abdominal pain (RAP) has a prevalence of 8.4% in childhood. In 90-95% of RAPs no organic disease is identified. Thus, it is important that the few of somatic origin are diagnosed. We describe a case concerning a 12-year-old girl, diagnosed with a solid pseudopapillary tumour of the pancreas. The symptoms were RAP and postprandial vomiting. The purpose of this article is to increase the knowledge of "alarm findings" indicating an organic disease in children with RAP. PMID:25292323

  5. Electrochemotherapy on liver tumours in rabbits.

    PubMed Central

    Ramirez, L. H.; Orlowski, S.; An, D.; Bindoula, G.; Dzodic, R.; Ardouin, P.; Bognel, C.; Belehradek, J.; Munck, J. N.; Mir, L. M.

    1998-01-01

    Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell-permeabilizing electric pulses (EPs) locally delivered to tumours. The transient permeabilization of the cell membrane by the EPs allows free access of BLM to its intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy has been proved so far on transplanted subcutaneous murine tumours and on subcutaneous metastases in humans. Here, we present the first study of the effects of ECT on tumours transplanted to livers in rabbits. We used a recently developed EP applicator consisting of an array of parallel and equidistant needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed by histological analysis, tumour growth rates and survival of the treated animals. A transient blood hypoperfusion was seen in the electropulsed areas, with or without BLM, related to EP-dependent vasoconstriction but this had no major effects on cell survival. Long-term effects depended on the presence of BLM at the time of EP delivery. Almost complete tumour necrosis was observed after ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized tumour cells and indirect effects on the tumour vessels. A large reduction in tumour growth rate and significantly longer survival times were scored in comparison with control rabbits. Moreover, ECT of liver tumours was well tolerated and devoid of systemic side-effects. When ECT was associated with a local interleukin 2-based immunotherapy, increased local anti-tumour effectiveness as well as a large decrease in the number of metastases were observed. Thus, ECT could become a novel treatment modality for liver tumours and other solid internal malignancies. Images Figure 1 Figure 2 PMID:9649121

  6. New technologies to combat malignant tumours of the brain.

    PubMed

    Heppner, F

    1982-01-01

    1. The primary problem in an effective treatment of a glioblastoma is the prevention of a recurrence. 2. For that purpose were the following therapeutical procedures undertaken: (a) Temporary implantation of radio cobalt in the brain itself (1957): (b) Clostridium butyricum M 55 was used to render the centre of the tumour fluid (1967): (c) Podophyllin was used to destroy the border of the tumour (1980); (d) The CO2 Laser beam (1975); (e) The electromagnetic heat induction deep in the brain (1973-1978). 3. In order to make the operation and postoperative phase safer for the patient, the following precautions were drawn upon or employed: (a) Hyperbaric oxygenisation in the pressure chamber (1971); (b) The anti-G-suit (1974); (c) the computer controlled automatic infusion pump (1980), and (d) the telemetric measurement of intra-cranial pressure (1975). 4. Apart from the pressure chamber, the mentioned devices were all supervised and developed in the department of the author. 5. The first successful means in the prevention of the recurrence of a glioblastoma multiform seems to be the telethermic method mentioned in 2 (e) above. PMID:6287907

  7. Transillumination imaging of intraocular tumours.

    PubMed

    Kjersem, Bård; Krohn, Jørgen

    2013-06-01

    The purpose of this paper is to discuss a recently described modification of a standard photo slit lamp system for ocular transillumination, with special emphasis on the light transmission through the eye wall and the photographic technique. Transillumination photography was carried out with the Haag-Streit Photo-Slit Lamp BX 900 (Haag-Streit AG, Koeniz, Switzerland). After having released the background lighting optic fibre cable from its holder, the patient was positioned at the slit lamp, and the fibre tip was gently pressed against the sclera or the cornea of the patient's eye. During about 1/1000 of a second, the eye was illuminated by the flash and the scleral shadow of the tumour was exposed to the camera sensor. The images were of good diagnostic quality, making it easy to outline the tumours and to evaluate the involvement of intraocular structures. None of the examined patients experienced discomfort or negative side effects. The method is recommended in cases where photographic transillumination documentation of intraocular pathologies is considered important. PMID:23641762

  8. Retrograde peri-implantitis.

    PubMed

    Mohamed, Jumshad B; Shivakumar, B; Sudarsan, Sabitha; Arun, K V; Kumar, T S S

    2010-01-01

    Retrograde peri-implantitis constitutes an important cause for implant failure. Retrograde peri-implantitis may sometimes prove difficult to identify and hence institution of early treatment may not be possible. This paper presents a report of four cases of (the implant placed developing to) retrograde peri-implantitis. Three of these implants were successfully restored to their fully functional state while one was lost due to extensive damage. The paper highlights the importance of recognizing the etiopathogenic mechanisms, preoperative assessment, and a strong postoperative maintenance protocol to avoid retrograde peri-implant inflammation. PMID:20922082

  9. Classification of odontogenic tumours. A historical review.

    PubMed

    Philipsen, Hans Peter; Reichart, Peter A

    2006-10-01

    Using the term odontome for any tumour arising from the dental formative tissues, Broca suggested a classification of odontogenic tumours (OTs) in 1869. From 1888 to 1914, Bland-Sutton and Gabell, James and Payne modified tumour terminology, while maintaining Broca's odontome concept. Thoma and Goldman's classification (1946) divided the OTs into tumours of ectodermal, mesodermal and mixed origin and abolished the general term odontome. The Pindborg and Clausen classification (1958) based on the idea that the reciprocal epithelial-mesenchymal tissue interactions were also operating in the pathogenesis of OTs. In 1966, WHO established a Collaborating Centre for the Histological Classification of Odontogenic Tumours and Allied Lesions (including jaw cysts) headed by Dr Jens Pindborg. In 1971, the first authoritative WHO guide to the classification of OTs and cysts appeared followed in 1992 by a second edition. In 2002, Philipsen and Reichart produced a revision of the 1992-edition and in 2003, the editors of the WHO Blue Book series: 'WHO Classification of Tumours' decided to produce a volume on the Head and Neck Tumours including a chapter on Odontogenic Tumours and Bone Related Lesions. In July of 2005 this volume was published by IARC, Lyon. PMID:16968232

  10. Cerebrospinal fluid rhinorrhoea in pituitary tumours1

    PubMed Central

    Cole, I E; Keene, Malcolm

    1980-01-01

    Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123

  11. Peculiarities of hyperlipidaemia in tumour patients.

    PubMed Central

    Dilman, V. M.; Berstein, L. M.; Ostroumova, M. N.; Tsyrlina, Y. V.; Golubev, A. G.

    1981-01-01

    The study group included 684 cases: 258 patients with breast carcinoma, 113 males with lung cancer, 42 patients with rectal tumours, 42 patients with stomach tumours, 59 patients with fibroadenomatosis, and 170 healthy subjects of varying age (male and female). A relatively high blood triglyceride level was found in patients with breast, lung, rectal (females), and stomach (female) tumours. The blood concentration of high-density lipoprotein-cholesterol in patients with breast, lung, and stomach (female) tumours was relatively low. The elimination of tumour (breast carcinoma) did not lead to significant changes in lipid metabolism. There was no correlation between degree of lipidaemia and stage of tumour progression except in the cases of rectal cancer. Preliminary results are presented on the tentative classification of hyperlipoproteinaemia in tumour patients, using the lipid concentration threshold values advocated by Carlson et al. (1977); an increased frequency of Type IV hyperlipoproteinaemia proved to be the most characteristic feature of tumour patients. The results are discussed in terms of the concept of the importance of lipid metabolic disturbances, primarily those due to ageing, in the genesis of the syndrome of "cancerophilia" (predisposition to cancer). PMID:7248149

  12. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  13. Strain elastography features of epidermoid tumours in superficial soft tissue: differences from other benign soft-tissue tumours and malignant tumours

    PubMed Central

    Park, H J; Lee, S M; Kim, W T; Lee, S; Ahn, K S

    2015-01-01

    Objective: We evaluated ultrasonographic features of superficial epidermoid tumour with a focus on strain elastography (SE) features that will help in the differential diagnosis of epidermoid tumour from other benign and malignant soft-tissue tumours. Methods: We retrospectively evaluated ultrasonographic and SE data of 103 surgically confirmed superficial soft-tissue tumours and tumour-like lesions: 29 cases of epidermoid tumour, 46 cases of other benign tumours and 28 cases of malignant tumour. SE and B-mode imaging were performed at the same time. SE characteristics were assigned into four grades (1–4) according to their elasticity. Interobserver agreement for the four SE scores between the two radiologists was analysed using kappa statistics. We classified each SE finding as a hard lesion (SE Score 3–4) or soft lesion (SE Score 1–2) and compared these findings using the χ2 test to identify whether a significant difference in mass hardness existed among epidermoid tumour, other benign tumour and malignant tumour. Results: Overall interobserver agreement according to the four SE scores was moderate (κ = 0.540), and overall agreement for the hardness [soft (Score 1–2) or hard (Score 3–4)] was almost perfect (κ = 0.825). Malignant tumours showed higher SE scores (3–4, hard nature) than did epidermoid tumour or other benign soft-tissue tumours. There were no differences in SE score between epidermoid tumour and other benign tumours. Conclusion: Superficial epidermoid tumour exhibits a softer nature than does malignant tumour but does not have a different SE pattern from other benign tumours. Advances in knowledge: SE features of epidermoid tumour might be helpful in differentiating from other benign and malignant tumours. PMID:25827206

  14. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours.

    PubMed

    Ince, Tan A; Sousa, Aurea D; Jones, Michelle A; Harrell, J Chuck; Agoston, Elin S; Krohn, Marit; Selfors, Laura M; Liu, Wenbin; Chen, Ken; Yong, Mao; Buchwald, Peter; Wang, Bin; Hale, Katherine S; Cohick, Evan; Sergent, Petra; Witt, Abigail; Kozhekbaeva, Zhanna; Gao, Sizhen; Agoston, Agoston T; Merritt, Melissa A; Foster, Rosemary; Rueda, Bo R; Crum, Christopher P; Brugge, Joan S; Mills, Gordon B

    2015-01-01

    Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy. PMID:26080861

  15. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours

    PubMed Central

    Ince, Tan A.; Sousa, Aurea D.; Jones, Michelle A.; Harrell, J. Chuck; Agoston, Elin S.; Krohn, Marit; Selfors, Laura M.; Liu, Wenbin; Chen, Ken; Yong, Mao; Buchwald, Peter; Wang, Bin; Hale, Katherine S.; Cohick, Evan; Sergent, Petra; Witt, Abigail; Kozhekbaeva, Zhanna; Gao, Sizhen; Agoston, Agoston T.; Merritt, Melissa A.; Foster, Rosemary; Rueda, Bo R.; Crum, Christopher P.; Brugge, Joan S.; Mills, Gordon B.

    2015-01-01

    Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy. PMID:26080861

  16. Myoepithelial cells in canine mammary tumours.

    PubMed

    Sánchez-Céspedes, Raquel; Millán, Yolanda; Guil-Luna, Silvia; Reymundo, Carlos; Espinosa de Los Monteros, Antonio; Martín de Las Mulas, Juana

    2016-01-01

    Mammary tumours are the most common neoplasms of female dogs. Compared to mammary tumours of humans and cats, myoepithelial (ME) cell involvement is common in canine mammary tumours (CMT) of any subtype. Since ME cell involvement in CMT influences both histogenetic tumour classification and prognosis, correct identification of ME cells is important. This review describes immunohistochemical methods for identification of canine mammary ME cells used in vivo. In addition, phenotypic and genotypic methods to isolate ME cells for in vitro studies to analyse tumour-suppressor protein production and gene expression are discussed. The contribution of ME cells to both histogenetic classifications and the prognosis of CMT is compared with other species and the potential use of ME cells as a method to identify carcinoma in situ is discussed. PMID:26639832

  17. Phase I/II Clinical Trial of Encapsulated, Cytochrome P450 Expressing Cells as Local Activators of Cyclophosphamide to Treat Spontaneous Canine Tumours

    PubMed Central

    Michałowska, Monika; Winiarczyk, Stanislaw; Adaszek, Łukasz; Łopuszyński, Wojciech; Grądzki, Zbigniew; Salmons, Brian; Günzburg, Walter H.

    2014-01-01

    Based upon promising preclinical studies, a clinical trial was performed in which encapsulated cells overexpressing cytochrome P450 enzyme isoform 2B1 were implanted around malignant mammary tumours arising spontaneously in dogs. The dogs were then given cyclophosphamide, one of the standard chemotherapeutic agents used for the treatment of mammary tumours. The dogs were assessed for a number of clinical parameters as well as for reduction in tumour size. The treatment was well tolerated with no evidence of adverse reactions or side effects being associated with the administration of the encapsulated cells. Reductions in tumour size of more than 50% were observed for 6 out of the 11 tumours analysed while 5 tumours showing minor responses, i.e. stable disease. In contrast, the tumours that received cyclophosphamide alone showed only stable disease. Taken together, this data suggests that encapsulated cytochrome P450 expressing cells combined with chemotherapy may be useful in the local treatment of a number of dog mammary tumours and support the performance of further clinical studies to evaluate this new treatment. PMID:25028963

  18. Transurethral resection and degeneration of bladder tumour

    PubMed Central

    Li, Aihua; Fang, Wei; Zhang, Feng; Li, Weiwu; Lu, Honghai; Liu, Sikuan; Wang, Hui; Zhang, Binghui

    2013-01-01

    Introduction: We evaluate the efficacy and safety of transurethral resection and degeneration of bladder tumour (TURD-Bt). Methods: In total, 56 patients with bladder tumour were treated by TURD-Bt. The results in these patients were compared with 32 patients treated by current transurethral resection of bladder tumour (TUR-Bt). Patients with or without disease progressive factors were respectively compared between the 2 groups. The factors included recurrent tumour, multiple tumours, tumour ≥3 cm in diameter, clinical stage T2, histological grade 3, adenocarcinoma, and ureteral obstruction or hydronephrosis. Results: Follow-up time was 48.55 ± 23.74 months in TURD-Bt group and 56.28 ± 17.61 months in the TUR-Bt group (p > 0.05). In patients without progressive factors, no tumour recurrence was found and overall survival was 14 (100%) in the TURD-Bt group; 3 (37.50%) patients had recurrence and overall survival was 5 (62.5%) in the TUR-Bt group. In patients with progressive factors, 8 (19.05%) patients had tumour recurrence, overall survival was 32 (76.19%) and cancer death was 3 (7.14%) in TURD-Bt group; 18 (75.00%) patients had tumour recurrence (p < 0.05), overall survival was 12 (50.00%) (p < 0.01) and cancer death was 8 (33.33%) (p < 0.05) in TUR-Bt group. No significant complication was found in TURD-Bt group. Conclusion: This study suggests that complete resection and degeneration of bladder tumour can be expected by TURD-Bt. The surgical procedure is safe and efficacious, and could be predictable and controllable before and during surgery. We would conclude that for bladder cancers without lymph node metastasis and distal metastasis, TURD-Bt could be performed to replace radical TUR-Bt and preserve the bladder. PMID:24475002

  19. Low Dose, Low Cost Estradiol Pellets Can Support MCF-7 Tumour Growth in Nude Mice without Bladder Symptoms

    PubMed Central

    Dall, Genevieve; Vieusseux, Jessica; Unsworth, Ashleigh; Anderson, Robin; Britt, Kara

    2015-01-01

    MCF-7 cells are a slow growing estrogen receptor (ER) positive human breast cancer cell line that is commonly used to model estrogen responsive breast cancer cell growth in-vitro and tumour growth in-vivo. These tumours require estrogen supplementation, and in-vivo doses of between 0.72mg and 2mg estradiol pellets are commonly implanted in the dorsal flank of ovariectomised, immunocompromised mice. We wanted to grow MCF-7 tumours in immunocompromised mice without the need to be ovariectomised. When we treated immunocompromised mice with 0.72mg pellets to induce MCF7 tumour growth, the mice developed urosepsis. We have now shown that lower doses of estradiol pellets, 0.3mg and 0.5mg, induce elevated serum estrogen levels and maintain tumour growth, without causing urosepsis. Supplementation for only one week did not support sustained MCF7 tumour growth. In conclusion, 0.3mg and 0.5mg silastic pellets can be used to stimulate ER+ breast cancer growth in ovary-intact, immune compromised mice. PMID:26640593

  20. [34 epibulbar malignant tumours (author's transl)].

    PubMed

    Schwartzenberg, T; Vancea, P P; Dobrescu, G

    1979-02-01

    Based on a study of 34 cases, the authors make therapeutical and diagnostical references concerning the epibulbar malignant tumours. These were met with a frequency of 10% of the total amount of the malignant tumours of the visual apparatus. The most frequent setting were at the level of the bulbar conjunctiva and of the sclero-corneal limb, especially in front of the opening of the palpebral slit and in the temporal area. The histological examination of the tumours pointed out the following morphological types; epitheliomas (61%), especially spino-cellular, malignant melanomas (32%) and sarcomas (6%). The therapeutical attitude was the surgical one -- the accurate extirpation -- in the limited tumours, followed by radiotherapy when neoplasic lesions were found at the limit of section. In the invaded tumours, the exenteration of the orbit was performed followed by radiotherapy. On the terms of such a therapeutical conduct, the distant prognosis proved to be dependent on two factors: a. The early diagnosis, that is the stage of the therapeutical action. It is insisted upon the importance of the signs of malignization of some benign tumors: papillomas or naevi. b. The nature and origin of the tumour: the secondary tumours are more severe from the beginning. PMID:444115

  1. Phase congruency map driven brain tumour segmentation

    NASA Astrophysics Data System (ADS)

    Szilágyi, Tünde; Brady, Michael; Berényi, Ervin

    2015-03-01

    Computer Aided Diagnostic (CAD) systems are already of proven value in healthcare, especially for surgical planning, nevertheless much remains to be done. Gliomas are the most common brain tumours (70%) in adults, with a survival time of just 2-3 months if detected at WHO grades III or higher. Such tumours are extremely variable, necessitating multi-modal Magnetic Resonance Images (MRI). The use of Gadolinium-based contrast agents is only relevant at later stages of the disease where it highlights the enhancing rim of the tumour. Currently, there is no single accepted method that can be used as a reference. There are three main challenges with such images: to decide whether there is tumour present and is so localize it; to construct a mask that separates healthy and diseased tissue; and to differentiate between the tumour core and the surrounding oedema. This paper presents two contributions. First, we develop tumour seed selection based on multiscale multi-modal texture feature vectors. Second, we develop a method based on a local phase congruency based feature map to drive level-set segmentation. The segmentations achieved with our method are more accurate than previously presented methods, particularly for challenging low grade tumours.

  2. Telomerase activity in 144 brain tumours.

    PubMed Central

    Sano, T.; Asai, A.; Mishima, K.; Fujimaki, T.; Kirino, T.

    1998-01-01

    Unlimited proliferation in immortalized cells is believed to be highly dependent on the activity of telomerase, a ribonucleoprotein that synthesizes telomeric repeats onto chromosome ends. Using a polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay, we analysed telomerase activity in 99 benign and 45 malignant brain tumours. The TRAP assay results were quantitated by normalizing the telomerase activity of each specimen to that of human glioma cell line T98G to obtain the relative telomerase activity. Telomerase activity was also assessed visually from the autoradiograms as being positive or negative. One hundred and sixteen tumours with negative telomerase activity had null relative telomerase activity, whereas 28 tumours with positive telomerase activity had relative telomerase activities of 12-84.3% (mean 0% vs 36.1 +/- 19.3%, P < 0.0001). Thus, quantification of telomerase activity confirmed the results of the visual evaluation of telomerase activity on autoradiograms. Based on the assessment, malignant brain tumours had a higher positive rate of telomerase activity than benign tumours (57.8% vs 2.0%, P < 0.001). These data indicate that positive telomerase activity is strongly associated with malignant brain tumours and is rather rare in benign tumours, such as neurinomas or meningiomas. Images Figure 2 PMID:9635839

  3. Malignant sweat gland tumours: an update.

    PubMed

    Cardoso, José C; Calonje, Eduardo

    2015-11-01

    Cutaneous adnexal tumours can be a diagnostic challenge for the pathologist. This is particularly true in the case of tumours with sweat gland differentiation, due to a large number of rare entities, a multiplicity of names to designate the same neoplasms and consequent lack of consensus regarding their classification and nomenclature. In the traditional view, sweat gland tumours were divided into eccrine and apocrine. However, this has been challenged in recent years, and in fact many of these tumours may have both eccrine and apocrine variants. Some display more complex features and defy classification, due to the presence of other lines of differentiation, namely follicular and/or sebaceous (in the case of apocrine tumours, due to the close embryological relationship between apocrine glands, hair follicles and sebaceous glands). The present paper reviews and updates the basic concepts regarding the following malignant sweat gland tumours: apocrine carcinoma, porocarcinoma, hidradenocarcinoma, spiradenocarcinoma, cylindrocarcinoma, microcystic adnexal carcinoma and related entities, squamoid eccrine ductal carcinoma, digital papillary adenocarcinoma, primary cutaneous mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma and primary cutaneous signet ring cell carcinoma. Particular emphasis is put in recent findings that may have implications in the diagnosis and management of these tumours. PMID:26114606

  4. Appendiceal tumour--retrospective clinicopathological analysis.

    PubMed

    Machado, Norman O'Neil; Chopra, Pradeep; Pande, Girish

    2004-01-01

    Appendiceal tumours are rare and often discovered unexpectedly in an acute situation in which decision-making is difficult. We report the spectrum of appendiuar tumours seen in our institution over a period of more than 10 years, and discuss the clinicopathological behaviour, investigations, surgical procedures and outcomes in these patients. We have also reviewed the literature with regard to appendiceal tumours. Appendicular tumours were identified from the database of 1646 appendictomies (18% in children) performed in single centre and case notes were reviewed. Clinical presentation, investigations, histopathology, surgical procedures and outcome were analysed. Twelve patients with appendiceal tumours were identified (0.72%): 8 carcinoid, 2 mucinous (mucocele) and 2 adenocarcinoma. All the patients with a carcinoid tumour presented with features suggestive of acute appendicitis and were diagnosed postoperatively following appendicectomy and formal histology. No further surgical intervention was required as these lesions were less than 1cm away from the base of the appendix. One of the patient with mucinous cystadenoma presented acutely and underwent an appendicectomy; in the other patient with chronic pain, apreoperative MRI suggested the diagnosis leading to a planned hemicolectomy as the lesion was close to the base of the appendix. While one of the patient with an adenocarcinoma localized to the appendix did well following a right hemicolectomy, the other patient with disseminated disease succumbed within a year. Carcinoid tumours are the commonest appendiceal tumours, which present often as acute appendicitis. While appendicectomy would be adequate in most of these patients, in patients with a cystadenoma close to the base of the appendix or in case of a carcinoma, a right hemicolectomy is the appropriate option. While the prognosis is good in patients with carcinoid tumour and cystadenoma, it remains dismal in patients with disseminated malignant disease

  5. Primary Axillary Porocarcinoma: A Rare Cutaneous Tumour.

    PubMed

    Devi, Nalli R Sumitra; Valarmathi, K; Lilly, Mary; Satish, Selvi; Mishra, Nidhi

    2016-02-01

    Eccrine porocarcinoma, a rare cutaneous malignant tumour accounts for a fraction of sweat gland tumours. This tumour is found to originate from the intraepithelial parts of the sweat glands. It commonly involves the lower extremities in elderly patients and carries an aggressive behaviour. Cutaneous and visceral metastasis can occur and hence prompt treatment is mandatory. Surgical excision is the mainstay of treatment modality. We hereby present a case of eccrine porocarcinoma in a 50-year-old male in the right axillary region presenting as a verrucous lesion. PMID:27042472

  6. Primary Axillary Porocarcinoma: A Rare Cutaneous Tumour

    PubMed Central

    Valarmathi, K.; Lilly, Mary; Satish, Selvi; Mishra, Nidhi

    2016-01-01

    Eccrine porocarcinoma, a rare cutaneous malignant tumour accounts for a fraction of sweat gland tumours. This tumour is found to originate from the intraepithelial parts of the sweat glands. It commonly involves the lower extremities in elderly patients and carries an aggressive behaviour. Cutaneous and visceral metastasis can occur and hence prompt treatment is mandatory. Surgical excision is the mainstay of treatment modality. We hereby present a case of eccrine porocarcinoma in a 50-year-old male in the right axillary region presenting as a verrucous lesion. PMID:27042472

  7. Photodynamic therapy and anti-tumour immunity

    PubMed Central

    Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R.

    2010-01-01

    Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636

  8. The prophylaxis of nonindustrial urothelial tumours

    PubMed Central

    Mount, Balfour M.

    1973-01-01

    Present knowledge concerning carcinogenesis and the natural history of urothelial tumours precludes firm conclusions relative to nonindustrial prophylaxis. However, a number of measures are consistent with current data and may be instituted for those patients with a demonstrated propensity to urothelial tumours. Their acceptability is based on the lack of associated toxicity for the patient. These measures include the elimination of significant infection, cigarettes, artificial sweeteners, analgesic abuse and coffee, the administration of vitamins C and B6, and in selected cases, the use of thiotepa. It is emphasized that the merit of these steps in altering the natural history of urothelial tumours is uncertain. PMID:4197537

  9. Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model

    PubMed Central

    Broadhead, M L; Dass, C R; Choong, P F M

    2011-01-01

    Background: Pigment epithelium-derived factor (PEDF) is an endogenous glycoprotein with a potential role as a therapeutic for osteosarcoma. Animal studies have demonstrated the biological effects of PEDF on osteosarcoma; however, these results are difficult to extrapolate for human use due to the chosen study design and drug delivery methods. Methods: In this study we have attempted to replicate the human presentation and treatment of osteosarcoma using a murine orthotopic model of osteosarcoma. The effects of PEDF on osteosarcoma cell lines were evaluated in vitro prior to animal experimentation. Orthotopic tumours were induced by intra-tibial injection of SaOS-2 osteosarcoma cells. Treatment with PEDF was delayed until after the macroscopic appearance of primary tumours. Pigment epithelium-derived factor was administered systemically via an implanted intraperitoneal micro-osmotic pump. Results: In vitro, PEDF inhibited proliferation, induced apoptosis and inhibited cell cycling of osteosarcoma cells. Pigment epithelium-derived factor promoted adhesion to Collagen I and inhibited invasion through Collagen I. In vivo, treatment with PEDF caused a reduction in both primary tumour volume and burden of pulmonary metastases. Systemic administration of PEDF did not cause toxic effects on normal tissues. Conclusion: Systemically delivered PEDF is effective in suppressing the size of primary and secondary tumours in an orthotopic murine model of osteosarcoma. PMID:21979423

  10. Beneficial role of overexpression of TFPI-2 on tumour progression in human small cell lung cancer☆

    PubMed Central

    Lavergne, Marion; Jourdan, Marie-Lise; Blechet, Claire; Guyetant, Serge; Pape, Alain Le; Heuze-Vourc’h, Nathalie; Courty, Yves; Lerondel, Stephanie; Sobilo, Julien; Iochmann, Sophie; Reverdiau, Pascale

    2013-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin, a protease which is involved in tumour progression by activating (MMPs). This therefore makes TFPI-2 a potential inhibitor of invasiveness and the development of metastases. In this study, low levels of TFPI-2 expression were found in 65% of patients with small cell lung cancer (SCLC), the most aggressive type of lung cancer. To study the impact of TFPI-2 in tumour progression, TFPI-2 was overexpressed in NCI-H209 SCLC cells which were orthotopically implanted in nude mice. Investigations showed that TFPI-2 inhibited lung tumour growth. Such inhibition could be explained in vitro by a decrease in tumour cell viability, blockade of G1/S phase cell cycle transition and an increase in apoptosis shown in NCI-H209 cells expressing TFPI-2. We also demonstrated that TFPI-2 upregulation in NCI-H209 cells decreased MMP expression, particularly by downregulating MMP-1 and MMP-3. Moreover, TFPI-2 inhibited phosphorylation of the MAPK signalling pathway proteins involved in the induction of MMP transcripts, among which MMP-1 was predominant in SCLC tissues and was inversely expressed with TFPI-2 in 35% of cases. These results suggest that downregulation of TFPI-2 expression could favour the development of SCLC. PMID:23905012

  11. Urinary incontinence - injectable implant

    MedlinePlus

    Injectable implants are injections of material into the urethra to help control urine leakage ( urinary incontinence ) caused by a ... into the tissue next to the sphincter. The implant procedure is usually done in the hospital. Or ...

  12. Hair implant complications.

    PubMed

    Hanke, C W; Norins, A L; Pantzer, J G; Bennett, J E

    1981-04-01

    Four men who underwent hair implantation for pattern baldness were treated for complications such as infection, foreign-body reaction, pruritus, and scarring. The complications were similar to those reported with synthetic modacrylic fiber implants that have been used for the same purpose. Although we believe this is the first article to report complications from hair implants, the illogical basis of the procedure suggests that complications will occur in many unsuspecting patients who undergo hair implantation. PMID:7009899

  13. [Clinical types of thoracic cancer. Mediastinal tumours].

    PubMed

    Lemarié, E

    2006-11-01

    Mediastinal germ cell tumours (teratomas, seminomas, and non-seminomatous malignant germ cell tumours) are a heterogeneous group of benign and malignant neoplasms. The standard treatment of mediastinal non-seminomatous malignant germ cell tumours is four cycles of chemotherapy followed by surgical resection of the residual mass. Small localized mediastinal seminomas may be treated with primary resection followed by radiotherapy. In patients with locally advanced disease, the preferred treatment is systemic chemotherapy followed by surgical resection of any residual disease. Thymomas can be locally invasive and associated with parathymic syndromes. Complete surgical excision is attempted in most cases of thymoma. Radiation therapy is usually recommended for invasive or incompletely excised tumours. Invasive thymoma is chemosensitive. PMID:17268355

  14. A rare solitary fibrous tumour of kidney.

    PubMed

    Pathak, Tilak Bahadur; Nepal, Umesh

    2013-01-01

    A solitary fibrous tumour is an unusual spindle cell neoplasm. It frequently arises from the serosal surface of pleural cavity but has recently been described in diverse extrapleural sites. Urogenital localization is rare and only 36 cases of solitary fibrous tumours of the kidney have been described on published report. We report a case of a large solitary fibrous tumour clinically and radiologically thought to be renal cell carcinoma arising in the kidney of a 30 year old female. The radical nephrectomy was performed. The tumour was a well- circumscribed, solid mass attached to the renal pelvis without necrosis and haemorrhage. Histopathologically, a spindle cell neoplasia with alternating hypo and hypercellular areas, storiform, fascicular and hemangipericytoma like growth pattern and less cellular dense collagen deposits were observed. Immunohistochemical studies revealed reactivity for CD34, CD99 and Bcl-2 protein. PMID:24362666

  15. Chemotherapy sensitivity testing in human tumours.

    PubMed Central

    Richmond, H G; Billington, R W

    1981-01-01

    We have attempted to establish in vitro growth in a consecutive series of 245 malignant tumours submitted for routine histopathology. Initially, three disaggregation procedures were used: mechanical separation, digestion by trypsin, and digestion by collagenase. The resulting cell fractions had varying success rates in establishing growth. Abundant epithelial cell growth was achieved in monolayer culture in 63 tumours, and the sensitivity of the cells to cytotoxic agents was tested. There was no indiscriminate cytotoxic effect, and each tumour type varied in its sensitivity from one patient's lesion to another. While testing of all solid tumours is not possible with present-day techniques, we believe that the employment of in vitro sensitivity testing as a routine procedure may be possible in the future if a suitable system giving correlation between in vitro and in vivo sensitivity can be developed. Images PMID:7240421

  16. The International Histological Classification of Tumours*

    PubMed Central

    Sobin, L. H.

    1981-01-01

    This article reviews the development of the WHO project on the histological classification of tumours, which has included the establishment of several collaborating centres and has involved more than 300 pathologists in over 50 countries. The project has resulted in the publication, over the last 14 years, of 25 volumes in the first series of the International Histological Classification of Tumours (IHCT), each giving a classification of tumours specific to a certain site. The classifications are based primarily on the microscopic characteristics of the tumours and are concerned with morphologically identifiable cell types and histological patterns as seen by means of light microscopy and conventional staining techniques. The article also describes the relationship between IHCT and other classification and coding systems and assesses possible future developments that may result from new approaches to diagnosis. PMID:6978190

  17. Imaging tumour hypoxia with positron emission tomography

    PubMed Central

    Fleming, I N; Manavaki, R; Blower, P J; West, C; Williams, K J; Harris, A L; Domarkas, J; Lord, S; Baldry, C; Gilbert, F J

    2015-01-01

    Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers. PMID:25514380

  18. Dentigerous Cyst Associated with Adenomatoid Odontogenic Tumour

    PubMed Central

    Majumdar, Sumit; Uppala, Divya; Talasila, Sunil; Babu, Mahesh

    2015-01-01

    Adenomatoid odontogenic tumour (AOT), a tumour composed of odontogenic epithelium, is an uncommon tumour of odontogenic origin that accounts for only 2.2- 7.1% of all odontogenic tumours. Very few cases of AOT associated with Dentigerous cyst (DC) have been reported till date, most cases are in females and have a striking tendency to occur in the anterior maxilla. The present case is that of a 14-year-old female who revealed a large radiolucent lesion associated with the crown of an unerupted canine located in the left maxillary anterior region. The microscopic examination revealed the presence of AOT in the fibrous capsule of a DC. In this paper, we describe the importance of grossing, sectioning and complete examination of the slide to diagnose such hybrid lesions. PMID:26155575

  19. Primary malignant tumours of the duodenum.

    PubMed

    Nix, G A; Wilson, J H; Dees, J

    1985-04-01

    The clinical and radiological findings in 19 patients with primary duodenal malignancy are described. Weight loss, abdominal pain, nausea and vomiting were the main symptoms. Diagnosis was made by endoscopy or ERCP (71%) or by barium studies (68%). In retrospect the tumour was visible in 97% of the studies. Tumour growth was longitudinal, circular or spiral, the inner curvature being involved over a greater length than the outer curvature. Exophytic tumour growth, involvement of the papilla of Vater, malignant spikes, transient, non-constant tumour image, skip lesions and ulceration were often seen. Mean survival time was 18 months from start of symptoms in 10 inoperable patients, and 24 months in 9 patients undergoing resection. PMID:2986213

  20. Implantable Heart Aid

    NASA Technical Reports Server (NTRS)

    1984-01-01

    CPI's human-implantable automatic implantable defibrillator (AID) is a heart assist system, derived from NASA's space circuitry technology, that can prevent erratic heart action known as arrhythmias. Implanted AID, consisting of microcomputer power source and two electrodes for sensing heart activity, recognizes onset of ventricular fibrillation (VF) and delivers corrective electrical countershock to restore rhythmic heartbeat.

  1. Intramuscular Hibernoma: A Rare Tumour in Buttock

    PubMed Central

    Naik, Reena; Kushwaha, Anil KU; Agrawal, P.C.

    2015-01-01

    Hibernomas are benign tumours of brown fat that does not recur after complete excision. These tumours are found most often in adults and most commonly in thigh. Four morphologic variants of hibernoma are identified: typical, myxoid, spindle cell, and lipoma-like. The most common histologic type is typical variant. In this report, we present the clinical, morphological features and discuss the differential diagnosis of a typical variant of intramuscular hibernoma. PMID:26266129

  2. Antenatally detected solid tumour of kidney

    PubMed Central

    Panda, Shasanka Shekhar; Mandelia, Ankur; Gupta, Devendra Kumar; Singh, Amit

    2014-01-01

    Congenital renal tumours are rare and usually benign. Polyhydramnios is the most common mode of presentation. Although most cases have been diagnosed postnatally, with advances in imaging technology, an increasing number of cases are being detected on antenatal scans. We describe a case of solid tumour of kidney detected in the second trimester of pregnancy and managed by surgery in the postnatal period. PMID:24526198

  3. Skull metastasis from rectal gastrointestinal stromal tumours.

    PubMed

    Gil-Arnaiz, Irene; Martínez-Trufero, Javier; Pazo-Cid, Roberto Antonio; Felipo, Francesc; Lecumberri, María José; Calderero, Verónica

    2009-09-01

    Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract. Rectum localisation is infrequent for these neoplasms, accounting for about 5% of all cases. Distant metastases of GIST are also rare. We present a patient with special features: the tumour is localised in rectum and it has an uncommon metastatic site, the skull, implying a complex differential diagnosis approach. PMID:19776004

  4. Epithelial odontogenic tumours in domestic animals.

    PubMed

    Walsh, K M; Denholm, L J; Cooper, B J

    1987-09-01

    Epithelial odontogenic tumours are uncommon, poorly understood and often difficult to diagnose, oral neoplasms. Dental organ pre-ameloblasts and basal lamina induce development of mesenchymal cells into odontoblasts, which produce dentin and induce pre-ameloblasts to mature into secretory ameloblasts. These reciprocal sequential inductive interactions between dental epithelium and mesenchyme form the basis for classifying epithelial odontogenic tumours. There are three tumours classified as non-inductive: ameloblastoma characterized by cords and islands of stellate reticulum with peripheral palisades of polarized columnar cells, adenomatoid ameloblastoma which has acini, rosettes and ducts of polarized columnar cells and stellate reticulum and calcifying epithelial odontogenic tumour which contains foci of Congo-red-positive material surrounded by pleomorphic polygonal epithelial cells. There are five tumours in which induction of mesenchymal tissue is evident: ameloblastic fibroma with characteristics of ameloblastoma plus proliferation of closely associated pulp-like mesenchyme; dentinoma consisting of masses of dentin, often with minimal cellular component; ameloblastic odontoma which contains palisaded epithelium and stellate reticulum as in ameloblastoma, as well as foci of dentin and/or enamel; complex odontoma which is a disorderly array of dentin, enamel, ameloblastic epithelium and odontoblasts; and compound odontoma containing denticles with well-organized tooth morphology. This paper reviews the embryogenesis of teeth and describes six types of epithelial odontogenic tumours in 13 animals. The literature concerning these tumours in nearly 250 animals is reviewed. The most commonly reported tumour is ameloblastoma and the species in which all types are most commonly reported is the dog. PMID:3316314

  5. Ovarian stimulation and granulosa-cell tumour.

    PubMed

    Willemsen, W; Kruitwagen, R; Bastiaans, B; Hanselaar, T; Rolland, R

    1993-04-17

    Ovarian stimulation in the treatment of infertility is far from physiological because patients and their ovaries are exposed to high concentrations of gonadotropins. Many studies have focused on the two most common side-effects of ovarian stimulation--ie, hyperstimulation and multiple pregnancy. We describe 12 patients in whom granulosa-cell tumour was discovered after ovarian stimulation treatment with clomiphene citrate and/or gonadotropins. Although we cannot prove a causal link between the tumour and the medication, investigations in animals have shown a relation between gonadotropin exposition and the development of granulosa-cell tumours. The possible relation of ovarian stimulation and granulosa-cell tumours in human beings has not been published before. We postulate three explanations for this finding; first, the granulosa-cell tumour is present in the ovary, waiting for a hormonal trigger; second, increased follicle stimulating hormone concentrations are oncogenic to granulosa cell; and third, the onset of the granulosa-cell tumour during ovarian stimulation is coincidental. We recommend that ovarian stimulation is done only if there is a valid indication after proper assessment of the ovaries, and that women who have had ovarian stimulation are followed for longer than at present. PMID:8096944

  6. Soft Tissue Tumours of the Retroperitoneum

    PubMed Central

    Van Roggen, J. Frans Graadt

    2000-01-01

    Purpose. This review summarizes the more prevalent soft tissue tumours arising in the retroperitoneum and highlights some recent fundamental and diagnostic developments relevant to mesenchymal tumours. Discussion. The retroperitoneum is an underestimated site for benign and malignant neoplastic disease, and represents the second most common site of origin of primary malignant soft tissue tumours (sarcomas) after the deep tissues of the lower extremity. In contrast to the predominance of benign soft tissue lesions over malignant sarcomas elsewhere, retroperitoneal mesenchymal lesions are far more likely to be malignant. The differential diagnosis is primarily with the more common lymphoproliferative and parenchymatous epithelial lesions arising in this area, and with metastatic disease from known or unknown primary sites elsewhere.The most prevalent mesenchymal tumours at this site are of a lipomatous, myogenic or neural nature.Their generally late clinical presentation and poorly accessible location provides numerous clinical challenges; optimal radiological imaging and a properly performed biopsy are essential cogs in the management route. Histopathological diagnosis may be complicated, but has been aided by developments in the fields of immunohistochemistry and tumour (cyto)genetics. Despite significant advances in oncological management protocols, the prognosis remains generally less favourable than for similar tumours at more accessible sites. PMID:18521430

  7. Consensus on biomarkers for neuroendocrine tumour disease

    PubMed Central

    Oberg, Kjell; Modlin, Irvin M; De Herder, Wouter; Pavel, Marianne; Klimstra, David; Frilling, Andrea; Metz, David C; Heaney, Anthony; Kwekkeboom, Dik; Strosberg, Jonathan; Meyer, Timothy; Moss, Steven F; Washington, Kay; Wolin, Edward; Liu, Eric; Goldenring, James

    2016-01-01

    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours. PMID:26370353

  8. Solitary fibrous tumour of the chest wall.

    PubMed

    Mohtarrudin, N; Nor Hanipah, Z; Mohd Dusa, N

    2016-04-01

    Extrapleural solitary fibrous tumours (SFTs) are rare tumours characterized by patternless spindle cells with haemangiopericytoma-like vascular spaces. Previously the tumours have been classified as haemangiopericytoma, an entity that is now considered obsolete. We report a case of extrapleural SFT arising in the soft tissue of the chest wall. The patient was a 31-year-old Malay lady presenting with a mobile swelling of the right chest wall for more than five years. During excision the tumour was noted to be well-circumscribed and yellowish in colour, giving an impression of lipoma. Microscopically, the tumour had patternless architecture, characterized by hypocellular and hypercellular areas. It was composed of uniform, spindle-shaped cells displaying oval nuclei, inconspicuous nucleoli, pale cytoplasm and indistinct cell borders. The mitotic count was 2 per 10 HPF. Branching, medium-sized thin-walled blood vessels in a haemangiopericytomatous growth pattern, some with hyalinised wall were identified. The neoplastic cells were immunoreactive to CD99 and CD34 and were non-immunoreactive to Desmin, Smooth Muscle Actin, S100 protein and EMA. We elucidate the challenges in diagnosing this tumour in this unusual location. PMID:27126667

  9. Oral inoculation of probiotics Lactobacillus acidophilus NCFM suppresses tumour growth both in segmental orthotopic colon cancer and extra-intestinal tissue.

    PubMed

    Chen, Chien-Chang; Lin, Wei-Chuan; Kong, Man-Shan; Shi, Hai Ning; Walker, W Allan; Lin, Chun-Yen; Huang, Ching-Tai; Lin, Yung-Chang; Jung, Shih-Ming; Lin, Tzou-Yien

    2012-06-01

    Modulation of the cellular response by the administration of probiotic bacteria may be an effective strategy for preventing or inhibiting tumour growth. We orally pre-inoculated mice with probiotics Lactobacillus acidophilus NCFM (La) for 14 d. Subcutaneous dorsal-flank tumours and segmental orthotopic colon cancers were implanted into mice using CT-26 murine colon adenocarcinoma cells. On day 28 after tumour initiation, the lamina propria of the colon, mesenteric lymph nodes (MLN) and spleen were harvested and purified for flow cytometry and mRNA analyses. We demonstrated that La pre-inoculation reduced tumour volume growth by 50·3 %, compared with untreated mice at 28 d after tumour implants (2465·5 (SEM 1290·4) v. 4950·9 (SEM 1689·3) mm³, P<0·001). Inoculation with La reduced the severity of colonic carcinogenesis caused by CT-26 cells, such as level of colonic involvement and structural abnormality of epithelial/crypt damage. Moreover, La enhanced apoptosis of CT-26 cells both in dorsal-flank tumour and segmental orthotopic colon cancer, and the mean counts of apoptotic body were higher in mice pre-inoculated with La (P<0·05) compared with untreated mice. La pre-inoculation down-regulated the CXCR4 mRNA expressions in the colon, MLN and extra-intestinal tissue, compared with untreated mice (P<0·05). In addition, La pre-inoculation reduced the mean fluorescence index of MHC class I (H-2Dd, -Kd and -Ld) in flow cytometry analysis. Taken together, these findings suggest that probiotics La may play a role in attenuating tumour growth during CT-26 cell carcinogenesis. The down-regulated expression of CXCR4 mRNA and MHC class I, as well as increasing apoptosis in tumour tissue, indicated that La may be associated with modulating the cellular response triggered by colon carcinogenesis. PMID:21992995

  10. Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight

    PubMed Central

    Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

    2015-01-01

    Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. PMID:25648860