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Sample records for implanted vx2 tumour

  1. Photodynamic therapy for implanted VX2 tumor in rabbit brains

    NASA Astrophysics Data System (ADS)

    Li, Fei; Feng, Hua; Lin, Jiangkai; Zhu, Gang; Chen, Zhi; Li, Cong-yan

    2005-07-01

    To evaluate the therapeutic effect and the safety of single photodynamic therapy (PDT) with hematoporphyrin derivative produced in China, 60 New Zealand adult rabbits with VX2 tumor implanted into the brain were divided randomly into non-PDT-group and PDT-group. 36 rabbits of the PDT-group were performed photodynamic therapy. The survival time, neurological deteriorations, intracranial pressure (ICP), histology, pathology, tumor volume and brain water content were measured. Other 12 rabbits were received hematoporphyrin derivative and light irradiation of the normal brain. The ICP, histology, pathology, and brain water content were measured. The result indicated that Simple PDT may elongate the average survival time of the rabbits with VX2 tumors significantly; kill tumor cells; cause transient brain edema and increase ICP, but it is safe to be used in treating brain tumor.

  2. Quantitative MRI assessment of VX2 tumour oxygenation changes in response to hyperoxia and hypercapnia

    NASA Astrophysics Data System (ADS)

    Winter, Jeff D.; Akens, Margarete K.; Cheng, Hai-Ling Margaret

    2011-03-01

    Magnetic resonance imaging (MRI) relaxation times provide indirect estimates of tissue O2 for monitoring tumour oxygenation. This study provides insight into mechanisms underlying longitudinal (R1 = 1/T1) and transverse effective (R2* = 1/T2*) relaxation rate changes during inhalation of 100% O2 and 3%, 6% and 9% CO2 (balanced O2) in a rabbit tumour model. Quantitative R1, R2*, and dynamic contrast-enhanced (DCE) imaging was performed in six rabbits 12-23 days following implantation of VX2 carcinoma cells in the quadricep muscle. Invasive measurements of tissue partial pressure of O2 (pO2) and perfusion were also performed, which revealed elevated pO2 levels in all tumour regions for all hyperoxic gases compared to baseline (air) and reduced perfusion for carbogen. During 100% O2 breathing, an R1 increase and R2* decrease consistent with elevated pO2 were observed within tumours. DCE-derived blood flow was weakly correlated with R1 changes from air to 100% O2. Further addition of CO2 (carbogen) did not introduce considerable changes in MR relaxation rates, but a trend towards higher R1 relative to breathing 100% O2 was observed, while R2* changes were inconsistent. This observation supports the predominance of dissolved O2 on R1 sensitivity and demonstrates the value of R1 over R2* for tissue oxygenation measures.

  3. Functional CT imaging of angiogenesis in rabbit VX2 soft-tissue tumour

    NASA Astrophysics Data System (ADS)

    Purdie, Thomas G.; Henderson, Elizabeth; Lee, Ting-Yim

    2001-12-01

    Functional parameters such as blood flow (BF), microvessel permeability surface area product (PS), blood volume (BV) and mean transit time (MTT) are physiological markers related to the changes associated with angiogenesis. In the current study we present a functional CT technique for the simultaneous measurement of these four functional parameters and the display of each parameter as a functional image over an entire tissue slice. New Zealand White rabbits with implanted VX2 thigh tumours were scanned using CT with contrast media injection. The ex vivo method of radioactive microspheres was used to evaluate the accuracy of BF measurements with the functional CT technique. There was a significant linear correlation (R = 0.96) between regional CT and microsphere-measured BF values, with a slope not significantly different from unity (0.98 +/- 0.02, P < 0.0001). The precision of our CT technique was determined by the repeated scanning under steady-state conditions. The precision of CT-measured BF, PS, BV and MTT was 14%, 18%, 20% and 24%, respectively. In conclusion, BF can be measured accurately and BF, PS, BV and MTT reproducibly using our functional CT technique. Functional CT can be readily incorporated into existing imaging protocols to assess tumour angiogenesis.

  4. Carbon dioxide reactivity of computed tomography functional parameters in rabbit VX2 soft tissue tumour

    NASA Astrophysics Data System (ADS)

    Purdie, Thomas G.; Lee, Ting-Yim

    2003-04-01

    Tumour blood flow is one of the important factors limiting the efficacy of radiation therapy (hypoxic radioresistance), chemotherapy (drug delivery) and thermal therapy (heat dissipation) in treating cancer. The modification of tumour blood flow has been an area of intense investigation. In the current study, the arterial carbon dioxide tension (PaCO2) was changed in order to investigate the tumour vascular response to carbon dioxide. Functional maps of blood flow, blood volume and mean transit time were generated at four PaCO2 levels in VX2 tumour in the rabbit thigh and normal soft tissue. The PaCO2 levels investigated were normocapnia (PaCO2 = 40.9 +/- 1.2 mmHg), hypocapnia (27.2 +/- 2.3 and 33.5 +/- 2.3 mmHg) and hypercapnia (54.9 +/- 4.4 mmHg). The carbon dioxide reactivity of the global tumour blood flow and mean transit time showed significant differences between normocapnia and the two levels of hypocapnia, but not between normocapnia and hypercapnia. The average fractional change of blood flow from normocapnia for the two levels of hypocapnia was -0.41 +/- 0.06 and -0.29 +/- 0.08, respectively (P < 0.05). In the case of mean transit time the fractional change was +0.39 +/- 0.30 and +0.23 +/- 0.24, respectively (P < 0.05). The fractional change of blood volume from normocapnia, however, was not significantly different at any capnic level, as was the case with respect to each of the functional parameters in normal tissue. The ability to reduce blood flow and increase mean transit time through hypocapnia has significant implications in thermal therapy, since heat dissipation is a major factor in limiting the effectiveness of treatment.

  5. 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.

  6. Evaluation of 70-150-μm doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model.

    PubMed

    Gholamrezanezhad, Ali; Mirpour, Sahar; Geschwind, Jean-Francois H; Rao, Pramod; Loffroy, Romaric; Pellerin, Olivier; Liapi, Eleni A

    2016-10-01

    To evaluate the pharmacokinetic profile (PK) and embolization effect of 70-150-μm doxorubicin eluting beads (DEBs) following intra-arterial injection (i.a.) in the rabbit liver VX2 tumour model. In this ACUC-approved study, 25 white New Zealand rabbits were randomly assigned into a small DEB group (SDB, n = 7, 70-150-μm DEBs), large DEB group (LDB, n = 7, 100-300-μm DEBs), untreated controls (n = 7), and doxorubicin controls (n = 4, without tumour, received i.a. 12.5 mg doxorubicin). Plasma PK was assessed up to 180 min post-injection. Drug tissue and liver enzyme levels, radiologic tumor response and histopathologic tumour necrosis were assessed at 7 days. Mean tumour doxorubicin concentrations were 922.83 nM (SD = 722.05) and 361.48 nM (SD = 473.23) for the SDB and LDB, respectively (p = 0.005). There was no statistically significant difference in tumour doxorubicinol, plasma doxorubicin and doxorubicinol PK values. More beads were observed in the SDB tumours (p = 0.01). Liver enzymes increased and gradually declined over the observation period, with significantly higher values in the SDB. In this preclinical study, plasma PK of i.a.-injected 70-150-μm DEBs was not different than that of 100-300-μm DEBs. More beads and higher tissue doxorubicin levels were observed in the SDB tumours. • Small and large doxorubicin-eluting beads show similar plasma pharmacokinetic profiles. • Higher tissue doxorubicin levels were observed in the small bead group. • Liver enzymes were overall significantly higher in the small bead group.

  7. Injectable PLGA/Fe3O4 implants carrying cisplatin for synergistic magnetic hyperthermal ablation of rabbit VX2 tumor.

    PubMed

    Yang, Yang; Wang, Fengjuan; Zheng, Kaiyuan; Deng, Liming; Yang, Lu; Zhang, Nan; Xu, Chunyan; Ran, Haitao; Wang, Zhaoxia; Wang, Zhigang; Zheng, Yuanyi

    2017-01-01

    Magnetic hyperthermia ablation has attracted wide attention in tumor therapy for its minimal invasion. Although the chemo-hyperthermal synergism has been proven to be effective in subcutaneously xenografted tumors of nude mice in our previous experiment, the occurrence of residual tumors due to incomplete ablation is more common in relatively larger and deeper-seated tumors in anti-tumor therapy. Thus, a larger tumor and larger animal model are needed for further study of the therapeutic efficacy. In this study, we tested the efficiency of this newly developed technique using a rabbit tumor model. Furthermore, we chose cisplatin (DDP), which has been confirmed with high efficiency in enhancing hyperthermia therapy as the chemotherapeutic drug for the synergistic magnetic hyperthermal ablation therapy of tumors. In vitro studies demonstrated that developed DDP-loaded magnetic implants (DDP/PLGA-Fe3O4) have great heating efficacy and the drug release can be significantly boosted by an external alternating magnetic field (AMF). In vivo studies showed that the phase-transitional DDP/PLGA-Fe3O4 materials that are ultrasound (US) and computerized tomography (CT) visible can be well confined in the tumor tissues after injection. When exposed to AMF, efficient hyperthermia was induced, which led to the cancer cells' coagulative necrosis and accelerating release of the drug to kill residual tumors. Furthermore, an activated anti-tumor immune system can promote apoptosis of tumor cells. In conclusion, the DDP/PLGA-Fe3O4 implants can be used efficiently for the combined chemotherapy and magnetic-hyperthermia ablation of rabbit tumors.

  8. Therapeutic efficacy of novel microwave-sensitized mPEG-PLGA@ZrO2@(DOX + ILS) drug-loaded microspheres in rabbit VX2 liver tumours.

    PubMed

    Mao, Jingsong; Tang, Shunsong; Hong, Duo; Zhao, Fan; Niu, Meng; Han, Xiangjun; Qi, Ji; Bao, Han; Jiang, Yutian; Fu, Changhui; Long, Dan; Meng, Xianwei; Su, Hongying

    2017-03-09

    The use of nanomaterials as drug delivery systems shows good effects in treating tumors. However, the effective dose of drugs targeted to tumor tissues is very low because of the effect of the reticuloendothelial system (RES) in removing such foreign substances. In order to eliminate the RES effect, we developed mPEG-PLGA@ZrO2@(DOX + ILS) (mPEG-PLGA@ZrO2@[DOX + ILS]) drug-loaded microspheres. These microwave (MW)-sensitized microspheres directly embolized the blood-supply vessels of tumors to induce tumor ischemia and hypoxia, as well as to aggregate drugs within tumor tissues in a long-lasting manner. Additionally, combination with MW ablation can triple the effects for the inhibition of tumor growth. The MW sensitive ionic liquid (ILS) in microspheres can rapidly produce a high temperature in a MW field on the basis of MW sensitization, thus accelerating the degradation of microspheres to release DOX-loaded ZrO2 into the lesions to kill tumors. Microspheres can also prolong the pharmacological time and effect of drugs through the enhanced permeability and retention (EPR) effect of nanocarriers, as well as the sustained release of nanomaterials. Studies performed in vivo revealed that mPEG-PLGA@ZrO2@(DOX + ILS) showed good biosafety. We undertook sensitized microsphere embolism therapy using novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres in a rabbit VX2 liver tumor model. Three, 6 and 9 d after treatment, computed tomography indicated no significant change in tumor size, and diffusion weighted imaging showed a marked decrease of residual tumor tissues. With the multiple functions of inducing embolisms, sensitization, and the sustained release of chemotherapeutics, novel mPEG-PLGA@ZrO2@(DOX + ILS) microspheres can achieve good therapeutic efficacy, in combination with MW ablation and chemotherapy, while embolizing the blood vessels of arterial tumors.

  9. Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model

    NASA Astrophysics Data System (ADS)

    Yu, Houqiang; Wang, Wei; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

    2017-03-01

    Ultrasound contrast agents (UCAs) such as SonoVue or Optison have been used widely in clinic for contrast-enhanced vascular imaging. However, microbubbles UCAs display limitations in tumor-targeted imaging due to the large sizes, nanoscaled UCAs has consequently attracted increasing attentions. In this work, we synthesized nanobubbles (NBs) by ultrasonic cavitation method, then a fluorescent marker of Alexa Fluor 680 was conjugated to the shell in order to observe the localization of NBs in tumor tissue. Measurement of fundamental characteristics showed that the NBs had homogeneous distribution of mean diameter of 267.9 +/- 19.2 nm and polydispersity index of 0.410 +/- 0.056. To assess in vivo tumor-selectivity of NBs, we established the rabbits VX2 hepatocellular carcinoma model though surgical implantation method. After the rabbits were intravenous administered of NBs, contrast-enhanced sonograms was observed in the surrounding of VX2 tumor, which showed there are rich capillaries in the tumor periphery. We additionally investigated the toxic of the NBs by hematoxylin-eosin staining. The results indicated that the NBs is a biocompatible non-toxic lipid system. Furthermore, the VX2 tumors and major organs were analyzed using ex vivo fluorescence imaging to confirm the targeted selectivity of NBs, and the results verified that the NBs were capable of targeting VX2 tumor. Confocal laser scanning microscopy examination showed that the NBs can traverse the VX2 tumor capillaries and target to the hepatocellular carcinoma tumor cells. All these results suggested that the newly prepared NBs have a potential application in molecular imaging and tumor-targeting therapy.

  10. 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.

  11. In vivo localized harmonic motion imaging of VX2 tumors

    NASA Astrophysics Data System (ADS)

    Curiel, Laura; Hynynen, Kullervo

    2012-10-01

    We evaluated the feasibility of localized harmonic motion (LHM) imaging for tumor detection in vivo. LHM was induced using a single-element focused ultrasound (FUS) transducer (80 mm focal, 100 mm diameter, 1.54 MHz) and a separate transducer (5 kHz PRF, 5 MHz) was used to track motion by cross-correlating RF signals. A scan was performed with the transducers assembly and LHM was induced 5 times per location. Images were formed averaging the calculated LHM amplitudes. Ten New Zealand rabbits had VX2 tumors implanted on their thighs. Tumors were located using Magnetic resonance images and LHM images were obtained. Eight out of ten tumors were visualized on LHM images as a region with lower amplitude (5.7±1.3μm in tumors and 19.5±5.8μm in muscle). All tumors had an elongated shape running along the muscle fibers. It was possible to detect tumors larger than 4mm in width (short axis of the tumor). We performed a FUS ablation of one tumor and the ablated region was detected as well on LHM images as a reduced LHM amplitude region.

  12. Cellular Imaging Using Equivalent Cross-Relaxation Rate Technique in Rabbit VX-2 Tumor Model.

    PubMed

    Nishiofuku, Hideyuki; Matsushima, Shigeru; Taguchi, Osamu; Inaba, Yoshitaka; Yamaura, Hidekazu; Sato, Yozo; Tanaka, Toshihiro; Kichikawa, Kimihiko

    2011-01-01

    Equivalent cross-relaxation rate (ECR) imaging (ECRI) is a measurement technique that can be used to quantitatively evaluate changes in structural organization and cellular density by MRI. The aim of this study was to evaluate the correlation between the ECR value and cellular density in the rabbit VX2 tumor model. Five rabbits implanted with 10 VX2 tumors in the femur muscles were included in this study. We adopted the off-resonance technique with a single saturation transfer pulse frequency of 7 ppm downfield from water resonance. The ECR value was defined as the percentage of signal loss between the unsaturated and saturated images. ECR images were constructed based on the percentage of the ECR value. Pathological specimens were divided into 34 areas and classified into two groups: the viable group and the necrotic group. ECR values were measured and compared between groups. The correlation between the ECR value and cellular density was then determined. The mean ECR value was significantly higher in the viable group than in the necrotic group (61.2% vs. 35.8%). The area under the curve that calculated by receiver operating characteristic curve was 0.991 at 7 ppm. The regression graph showed a linear relationship between the ECR value and cellular density; the correlation coefficient (r) was 0.858. There is a strong association between the ECR value and cellular density in VX2 tumors and so ECRI could be a potentially useful technique for accurately depicting viable and necrotic areas.

  13. Growth Inhibition of Tumour Implants by Associated Surface Active Agents

    PubMed Central

    Altman, R. F. A.; Spoladore, L. G.; Esch, E. L.

    1970-01-01

    Whereas dilute solutions of surface active agents modify the properties of cell membranes, particularly in relation to their electrical behaviour, moderate and strong solutions provoke more serious structural damage of the membrane, leading to an increase of its permeability and, finally, to cytolysis. These phenomena have inspired some authors to apply detergents as possible cancer chemotherapeuticals so far, however, with only poor results. The disintegrating effect of tumour emboli into single cells by certain detergents, and the ingenious discovery that the mutual adhesiveness between cancer cells is much less than between normal cells, have led the present authors to investigate the action of some biological surface active agents, alone as well as in some of their associations on the “take” of Yoshida sarcoma implants. Certain associations showed, in contradistinction to the separately applied components, surprisingly favourable activity. It could be established that a correlation actually exists between inhibitory effect and surface activity. PMID:4394469

  14. 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

  15. Sphere-forming-like cells (squamospheres) with cancer stem-like cell traits from VX2 rabbit buccal squamous cell carcinoma.

    PubMed

    Chen, Yuk-Kwan; Huang, Anderson Hsien-Cheng; Lin, Li-Min

    2014-12-01

    Previous studies have demonstrated that spheroid type cells grown under suspension culture conditions have cancer stem cell (CSC) traits in a number of cancers, but this phenomenon has not yet been reported in the VX2 rabbit oral cancer model. Hence, this study aimed to study the spheroid cells from VX2 rabbit buccal squamous cell carcinomas (SCCs) and assess their CSC characteristics. Five adult male New Zealand white outbred rabbits were used to generate VX2 rabbit buccal SCC. Sphere-forming cell culture was performed for the VX2 rabbit buccal SCC specimens. The self-renewal capability; cluster of designation (CD) 44, CD133, acetaldehyde dehydrogenase 1 (ALDH1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), Nestin, octamer-binding transcription factor 4 (Oct4) and reduced expression protein-1 (Rex-1) expression with reverse transcription-polymerase chain reaction (RT-PCR); chemoresistance to cisplatin and 5-fluorouracil; and in vivo tumorigenicity of spheroid cell transplantation in nude mice were evaluated to determine the CSC characteristics of the resulting spheroid cells. We successfully obtained spheroid cells from the VX2 rabbit OSCC tissues. The spheroid cells exhibited CSC traits, including the expression of CSC and stem cell markers (CD44, Bmi-1, Nestin, Oct4 and Rex-1), capacity to generate new spheroid colonies within 1 week of reseeding from single-dissociated spheroid cells, chemoresistance capacity and generation of tumour xenografts (with histological features resembling those of the original VX2 rabbit buccal SCC) from the transplantation of 10(3) undifferentiated spheroid cells into nude mice. In summary, we demonstrated that spheroid cells with CSC cell traits can be derived from VX2 rabbit buccal SCCs, indicating that this animal cancer model is applicable for studying CSCs in human oral cancers.

  16. Sphere-forming-like cells (squamospheres) with cancer stem-like cell traits from VX2 rabbit buccal squamous cell carcinoma

    PubMed Central

    Chen, Yuk-Kwan; Huang, Anderson Hsien-Cheng; Lin, Li-Min

    2014-01-01

    Previous studies have demonstrated that spheroid type cells grown under suspension culture conditions have cancer stem cell (CSC) traits in a number of cancers, but this phenomenon has not yet been reported in the VX2 rabbit oral cancer model. Hence, this study aimed to study the spheroid cells from VX2 rabbit buccal squamous cell carcinomas (SCCs) and assess their CSC characteristics. Five adult male New Zealand white outbred rabbits were used to generate VX2 rabbit buccal SCC. Sphere-forming cell culture was performed for the VX2 rabbit buccal SCC specimens. The self-renewal capability; cluster of designation (CD) 44, CD133, acetaldehyde dehydrogenase 1 (ALDH1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), Nestin, octamer-binding transcription factor 4 (Oct4) and reduced expression protein-1 (Rex-1) expression with reverse transcription-polymerase chain reaction (RT-PCR); chemoresistance to cisplatin and 5-fluorouracil; and in vivo tumorigenicity of spheroid cell transplantation in nude mice were evaluated to determine the CSC characteristics of the resulting spheroid cells. We successfully obtained spheroid cells from the VX2 rabbit OSCC tissues. The spheroid cells exhibited CSC traits, including the expression of CSC and stem cell markers (CD44, Bmi-1, Nestin, Oct4 and Rex-1), capacity to generate new spheroid colonies within 1 week of reseeding from single-dissociated spheroid cells, chemoresistance capacity and generation of tumour xenografts (with histological features resembling those of the original VX2 rabbit buccal SCC) from the transplantation of 103 undifferentiated spheroid cells into nude mice. In summary, we demonstrated that spheroid cells with CSC cell traits can be derived from VX2 rabbit buccal SCCs, indicating that this animal cancer model is applicable for studying CSCs in human oral cancers. PMID:25012868

  17. Enhancing tissue permeability with MRI guided preclinical focused ultrasound system in rabbit muscle: From normal tissue to VX2 tumor.

    PubMed

    Sun, Yao; Xiong, Xiaobing; Pandya, Darpan; Jung, Youngkyoo; Mintz, Akiva; Hayasaka, Satoru; Wadas, Thaddeus J; Li, King C P

    2017-06-28

    High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, (111)In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of (111)In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24h after systematic delivery of (111)In-DOTA-IA in VX2 tumors pretreated by pHIFU compared

  18. Intra- and interfractional variations in geometric arrangement between lung tumours and implanted markers.

    PubMed

    Ueki, Nami; Matsuo, Yukinori; Nakamura, Mitsuhiro; Mukumoto, Nobutaka; Iizuka, Yusuke; Miyabe, Yuki; Sawada, Akira; Mizowaki, Takashi; Kokubo, Masaki; Hiraoka, Masahiro

    2014-03-01

    To quantify the intra- and interfractional variations between lung tumours and implanted markers. Gold markers were implanted transbronchially around a lung tumour in fifteen patients. They underwent four-dimensional computed tomography scans twice, and the centroids of the tumour and markers were determined. Intrafractional variations were defined as the residual tumour motions relative to the markers due to respiration from the end-exhale phase. Interfractional variations were defined as the residual setup errors after correction for the position of the implanted markers in end-exhale phase images. The intrafractional variations differed between patients. The root mean squares of standard deviations for each phase were 0.6, 0.9, and 1.5mm in the right-left, anterior-posterior, and superior-inferior directions, respectively. The maximum difference in intrafractional variation among 10 phases was correlated with the amplitude of tumour motion in all directions and the tumour-marker distance in the anterior-posterior and superior-inferior directions. The interfractional variations were within 2.5mm. The intrafractional variations differed according to the amount of tumour motion and the tumour-marker distance. Additionally, interfractional variations of up to 2.5mm were observed. Thus, a corresponding margin should be considered during implanted marker-based beam delivery to account for these variations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Correlation between blood circulation grading and angiogenesis using ultrasonic contrast of rabbit VX2 hepatic carcinoma.

    PubMed

    Xu, Chang-Song; Su, Yi-Jin; Xu, Ming; Liu, Wei; Hao, Peng; Du, Lian-Fang

    2016-02-01

    To build the rabbit model of VX2 hepatic carcinoma, examine the tumor body using the ultrasonic contrast and study the correlation between the blood circulation grading and angiogenesis. The VX2 tumor strain was prepared in the lateral muscle of the hind legs of 40 male New Zealand rabbits (which were purchased from Nanjing Senbao Biotech Co., Ltd.). The tumor block was embedded in the center of left liver lobe directly to build the rabbit model of VX2 hepatic carcinoma. The ultrasonic contrast was performed 14 d after implanting the tumor body. The semi-quantitative classification (0-IV level) was taken according to the blood flow of tumor vessel. Animals were executed using the air embolism method. The liver was separated to extract RNA and total protein respectively. The real-time PCR and western blotting method were employed to detect the expression of angiogenesis-related factors of VEGF, bFGF and TNF-α, while the ultrasonic contrast to detect the correlation with blood circulation grading. The Pearson product moment correlation coefficient was used to measure the linear relationship between these two variables and analyze the correlation between the blood circulation grading and angiogenesis using the ultrasonic contrast. Thirty-three rabbits had the successful model of VX2 hepatic carcinoma. The blood circulation grading by ultrasonic contrast was: 2 cases at level 0 (6.60%), 5 cases at level I (16.7%), 12 cases at level II (40.0%), 6 cases at level III (20.0%) (local dense or clustered blood flow) and 5 cases at level IV (16.7%). The results showed that there was positive correlation between three angiogenesis-related factors and the blood circulation grading. The correlation coefficient between three angiogenesis-related factors and the blood circulation grading was over 0.9, which indicated the relatively high correlation. The ultrasound blood circulation grading for the hepatic carcinoma can clearly reflect the changes of blood vessel, which will be of

  20. Twin-screw extruded lipid implants containing TRP2 peptide for tumour therapy.

    PubMed

    Even, Marie-Paule; Bobbala, Sharan; Gibson, Blake; Hook, Sarah; Winter, Gerhard; Engert, Julia

    2017-01-16

    Much effort has been put in the development of specific anti-tumour immunotherapies over the last few years, and several studies report on the use of liposomal carriers for tumour-associated antigens. In this work, the use of lipid implants, prepared using two different extruders, was investigated for sustained delivery in tumour therapy. The implants consisted of cholesterol, soybean lecithin, Dynasan 114, trehalose, ovalbumin (OVA) or a TRP2 peptide, and Quil-A. Implants were first produced on a Haake Minilab extruder, and then a scale-down to minimal quantities of material on a small scale ZE mini extruder was performed. All formulations were characterised in terms of extrudability, implant properties and in vitro release behaviour of the model antigen ovalbumin. The type of extruder used to produce the implants had a major influence on implant properties and the release behaviour, demonstrating that extrusion parameters and lipid formulations have to be individually adapted to each extrusion device. Subsequently, lipid implants containing TRP-2 peptide were extruded on the ZE mini extruder and investigated in vitro and in vivo. The in vivo study showed that mice having received TRP2 loaded implants had delayed tumour growth for 3days compared to groups having received no TRP2.

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

    PubMed

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

    2009-06-07

    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.

  2. 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

  3. MRI image characteristics of materials implanted at sellar region after transsphenoidal resection of pituitary tumours

    PubMed Central

    Bladowska, Joanna; Bednarek-Tupikowska, Grażyna; Sokolska, Violetta; Badowski, Roman; Moroń, Krzysztof; Bonicki, Wiesław; Sąsiadek, Marek

    2010-01-01

    Summary Background: Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change in anatomical conditions. It depends also on numerous other factors, including: size and expansion of the tumour before surgery, type of surgical access, quality and volume of implanted materials and time of its resorption. The purpose was to demonstrate the characteristics of the implanted materials on MRI performed after transsphenoidal resection of pituitary tumours and to identify imaging criteria helpful in differential diagnosis of masses within the sellar region. Material/Methods: One hundred and fifty-four patients after transsphenoidal resection of pituitary tumours were included in the study. In general, 469 MRI examinations were performed with a 1.5T scanner. We obtained T1-weighted sagittal and coronal, enhanced and unenhanced images. In 102 cases, additional T2-weighted coronal, unenhanced images with 1.5 T unit were obtained as well. Results: The implanted materials appeared in 95 patient: fat in 86 and muscle with fascia in 3 patients. We could recognise implanted muscle and fascia in T2-weighted images, because of high signal intensity of the degenerating muscle and the line of low signal representing fascia. The implanted titanium mesh was found in 4 patients. Haemostatic materials were visible only in 2 patients in examinations performed at an early postoperative stage (1 month after the procedure). Conclusions: The knowledge of MRI characteristics of the materials implanted at the sellar region is very important in postoperative diagnosis of pituitary tumours and may help discriminate between tumorous and non-tumorous involvement of the sellar region. Some implanted materials, like fat, could be seen on MRI for as long as 10 years after the operation, others, like haemostatic materials, for only 1 month after surgery. T2-weighted imaging is a useful assessment method of the implanted muscle and fascia for a long time after surgery. PMID

  4. High-Resolution SPECT-CT/MR Molecular Imaging of Angiogenesis in the Vx2 Model

    PubMed Central

    Lijowski, Michal; Caruthers, Shelton; Hu, Grace; Zhang, Huiying; Scott, Michael J.; Williams, Todd; Erpelding, Todd; Schmieder, Anne H.; Kiefer, Garry; Gulyas, Gyongyi; Athey, Phillip S.; Gaffney, Patrick J.; Wickline, Samuel A.; Lanza, Gregory M.

    2009-01-01

    inhibition of 99mTc αvβ3-integrin-targeted nanoparticles at 22.2 MBq/kg reduced (P < 0.05) TMR (5.31 ± 0.06) to the nontargeted control contrast level. Multislice CT imaging could not distinguish the presence of Vx2 tumor implanted in the popliteal fossa from lymph nodes in the same fossa or in the contralateral leg. However, the use of 99mTc αvβ3-nanoparticles with SPECT-CT produced a clear neovasculature signal from the tumor that was absent in the nonimplanted hind leg. Using αvβ3-targeted 99mTc-gadolinium nanoparticles, the sensitive detection of the Vx2 tumor was extended to allow MR molecular imaging and 3D mapping of angiogenesis in the small tumor, revealing an asymmetrically distributed, patchy neovasculature along the periphery of the cancer. Conclusion Dual modality molecular imaging with αvβ3-targeted 99mTc-gadolinium nanoparticles can afford highly sensitive and specific localization of tumor angiogenesis, which can be further characterized with high-resolution MR neovascular mapping, which may predict responsiveness to antiangiogenic therapy. PMID:18836386

  5. Direct Quantification and Comparison of Intratumoral Hypoxia following Transcatheter Arterial Embolization of VX2 Liver Tumors with Different Diameter Microspheres.

    PubMed

    Levy, Elliot B; Gacchina Johnson, Carmen; Jacobs, Genevieve; Woods, David L; Sharma, Karun V; Bacher, John D; Lewis, Andrew L; Dreher, Matthew R; Wood, Bradford J

    2015-10-01

    To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an animal model of liver tumors. Inoculation of VX2 tumors in the left liver lobe was performed successfully in 12 New Zealand white rabbits weighing 3.7 kg ± 0.5 (mean ± SD). Tumors were deemed eligible for oxygen measurements when the maximum transverse diameter measured 15 mm or more by ultrasound examination. Direct monitoring of oxygenation of implanted rabbit hepatic VX2 tumors was performed with a fiberoptic electrode during and after transarterial embolization of the proper hepatic artery to angiographic flow stasis with microspheres measuring 70-150 μm, 100-300 μm, or 300-500 μm in diameter. Failure to achieve tumor hypoxia as defined despite angiographic flow stasis was observed in 10 of 11 animals. Embolization microsphere size effect failed to demonstrate a significant trend on hypoxia outcome among the diameters tested, and pair-wise comparisons of different embolic diameter treatment groups showed no difference in hypoxia outcome. All microsphere diameters tested resulted in similar absolute reduction (24.3 mm Hg ± 18.3, 29.1 mm Hg ± 1.8, and 19.9 mm Hg ± 9.3, P = .66) and percentage decrease in oxygen (56.0 mm Hg ± 23.9, 56.0 mm Hg ± 6.4, and 35.8 mm Hg ± 20.6, P = .65). Pair-wise comparisons for percent tumor area occupied by embolic agents showed a significantly reduced fraction for 300-500 μm diameters compared with 70-150 μm diameters (P < .05). In the rabbit VX2 liver tumor model, three tested microsphere diameters failed to cause tumor hypoxia as measured by a fiberoptic probe sensor according to the adopted hypoxia definitions. Copyright © 2015. Published by Elsevier Inc.

  6. Bioevaluation study of 32P-CP-PLLA particle brachytherapy in a rabbit VX2 lung tumor model.

    PubMed

    Xu, Yu ping; Yang, Min; Pan, Dong hui; Wang, Li zhen; Liu, Lu; Huang, Peilin; Shao, Guoqiang

    2012-04-01

    The purpose of this study was to investigate the therapy effects of intratumoral administration of (32)P-CP-PLLA particles in a rabbit VX2 lung tumor model. 16 rabbits with tumors were randomly divided into 4 groups. 4 rabbits served as untreated controls, and others received intratumoral administration of (32)P-CP-PLLA particles with CT guidance. The total radioactivities in treated groups were as follows: a low activity was 93 MBq (n=4) (group 1), a medium activity was 185 MBq (n=4) (group 2) and a high activity was 370 MBq (n=4) (group 3). Brachytherapy treated VX2 tumors underwent (18)F-FDG PET/CT at 0 day, 3 day, 7 day and 14 day postinjection. In control group, (18)F-FDG PET/CT images were acquired at the same time points but without any treatment. Bremsstrahlung SPECT images were performed at 14 days after intratumoral brachytherapy in treated groups. After Bremsstrahlung SPECT and last (18)F-FDG PET/CT imagings, the rabbits were euthanized and the tumors were removed for histological examination. Bremsstrahlung SPECT images study indicated that there was no leakage of (32)P out of the injection site at 14 days after treatment. Compared with the control, the tumor volumes in treated groups significantly decreased, and (32)P-CP-PLLA particle produced a reduction in maximum or mean SUV of VX2 tumor (p<0.05). The percentage changes in maximum and mean SUV gradually decreased in group 1 and group 2 from day 3 to day 14 (p<0.05). A transient increase in (18)F-FDG accumulation at group 3 occurred due to the inflammatory reaction elements. Activity dependence was seen in HE and PCNA staining after 14 days treatment among three treated groups (p<0.05). Our data suggested that (32)P-CP-PLLA particle localized on the injecting sites. This novel brachytherapy device efficiently suppressed the growth of the VX2 tumors implanted in the rabbit. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. [Effect of lipiodol emulsion and local hyperthermia on hepatic tissue blood flow in rabbits with VX-2 liver tumor].

    PubMed

    Suzuki, K; Tada, I; Okada, K; Kim, Y I; Kobayashi, M

    1988-08-01

    The effect of intra-arterial infusion of lipiodol-emulsion and local hyperthermia on tissue blood flow was examined in experimental hepatic tumor and normal liver of rabbits. VX-2 tumor was implanted in liver of rabbit. The tissue blood flow was estimated by hydrogen gas clearance method when the tumor grew to about 2 cm. Tissue blood flow in tumor (64.5 ml/min/100 g) was significantly less than in normal liver (90.8 ml/min/100 g) (p less than 0.005). The intra-arterial infusion of lipiodol-emulsion did not alter the flow in either tissue. However, the addition of hyperthermia induced a substantial rise of tissue blood flow in normal liver (35% increase, from 93.8 to 127 ml/min/100 g) when compared with in VX-2 tumor (8.9% increase, from 65.1 to 71.8 ml/min/100 g). These were accompanied by a selective heating of liver tumor; the tumor temperature rose to 43 degrees C, although that of normal liver remained at 38 degrees C. Our results suggested that a specific temperature rise of liver tumor after infusion of lipiodol-emulsion and local heating might be related to a different response of microcirculation in tumor and normal liver to the hyperthermia.

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

    PubMed

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

    2011-09-07

    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.

  9. 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.

  10. 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.

  11. Calcium hydroxyapatite ceramic implants in bone tumour surgery. A long-term follow-up study.

    PubMed

    Matsumine, A; Myoui, A; Kusuzaki, K; Araki, N; Seto, M; Yoshikawa, H; Uchida, A

    2004-07-01

    We reviewed the results of 51 patients with benign bone tumours treated by curettage and implantation of calcium hydroxyapatite ceramic (CHA). The mean follow-up was 11.4 years (10 to 15.5). Post-operative fractures occurred in two patients and three had local recurrences; three had slightly limited movement of the adjacent joint and one had mild osteoarthritis. There were no allergic or neoplastic complications. In all cases, radiographs showed that the CHA was well incorporated into the host bone. Statistical analysis showed that absorption of the implanted CHA was greater in males (odds ratio, 6.2; 95% CI, 1.6 to 23.7) and younger patients (odds ratio, 0.6 for increase in age of 10 years; 95% CI, 0.91 to 0.99). However, the implanted CHA was not completely absorbed in any patient. We conclude that CHA is a useful and safe bone substitute for the treatment of benign bone tumours.

  12. Arsenic trioxide treatment of rabbit liver VX-2 carcinoma via hepatic arterial cannulation-induced apoptosis and decreased levels of survivin in the tumor tissue.

    PubMed

    Li, Hong; Gong, Jian; Jiang, Xuyuan; Shao, Haibo

    2013-02-01

    To investigate the role of tumor apoptosis-inhibitory protein survivin in arsenic trioxide-induced apoptosis in VX-2 carcinoma in the rabbit liver by means of transcatheter arterial chemoembolization. Sixteen rabbits with 32 implanted hepatic VX-2 tumors were randomly divided into two groups. The experimental group received 2 mg of arsenic trioxide and 1 mL of ultra-fluid lipiodol co-injected via hepatic arterial cannulation and the control group received only 1 mL of lipiodol. Animals were sacrificed 3 weeks after trans-catheterial arterial chemoembolization. Tumor tissue and tumor-peripheral tissue were collected for analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining was used to assess tumor cells apoptosis. Immunohistochemistry was used to assess the presence of survivin protein. Reverse transcription polymerase chain reaction was used to determine the expression of survivin gene. The number of apoptotic cells significantly increased in the tumor tissue (5.20 ± 0.60%) compared to tumor-peripheral tissue (1.29 ± 0.42%) of the arsenic trioxide-treated group. Survivin expression levels in the tumor tissue were significantly reduced in arsenic trioxide-treated group (7.68 ± 0.65) compared to the control group (35.30 ± 4.63). Transcatheter arterial chemoembolization with arsenic trioxide induced apoptosis of VX-2 carcinoma, in which tumor apoptosis-inhibitory protein survivin may have played a role.

  13. Validation of VX2 as a Hepatocellular Carcinoma Model: Comparison of the Molecular Reaction of VX2 and HepG2 Tumor Cells to Sorafenib In Vitro.

    PubMed

    Nass, Norbert; Streit, Sebastian; Wybranski, Christian; Jürgens, Julian; Brauner, Jan; Schulz, Nadine; Powerski, Maciej; Ricke, Jens; Kalinski, Thomas; Dudeck, Oliver; Seidensticker, Max

    2017-01-01

    As there is currently no superior hepatocellular carcinoma (HCC) model with percutaneous vascular access for transarterial treatments available, the VX2 rabbit model is frequently used for in vivo investigations on liver carcinoma. However, the VX2 cell line was derived from a virus-induced skin papilloma that can form carcinosarcoma in liver of rabbits and the transferability of obtained results to HCC treatment remains open. Here we compared the most frequently investigated human HCC model cell line, HepG2, with VX2 cells in vitro in terms of sensitivity towards the broad specificity kinase inhibitor sorafenib and responsiveness to the addition of platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF), as well as insulin and interleukin-1β (IL1β). Phosphorylation of protein kinase B (AKT) the mitogen-activated protein kinases (MAPKs) p38 and p42/44 (extracellular signal-regulated kinase, ERK1/2) and inhibitor of kappa light chain gene enhancer alpha (IĸBα) was determined by western blotting as these events are associated with early signaling cascades. Additionally, the inhibition of phosphorylation under sorafenib treatment was investigated. Sorafenib was equally toxic to both cell lines, but only in HepG2 was activation of caspase 3/7 activity, as a sign of apoptosis, observed. VX2 cells exhibited generally more intense phosphorylation signals in response to the growth factors and also serum. In contrast to VX2, HepG2 cells showed no response to PDGF-AB or VEGF as determined by kinase phosphorylation. In both cell lines, sorafenib inhibited growth factor-induced phosphorylation of ERK and p38-MAPK. AKT phosphorylation was only inhibited in VX2 cells and IĸBα phosphorylation was not influenced by this kinase inhibitor in either cell type. Taken together, the two cellular models for HCC share several features related to sorafenib application, but differed in their responsiveness towards growth

  14. Monitoring of VX2 tumor growth in rabbit liver using T2-weighted and dynamic contrast-enhanced magnetic resonance imaging at 1.5T

    NASA Astrophysics Data System (ADS)

    Jao, Jo-Chi; Mac, Ka-Wai; Chang, Chiung-Yun; Wu, Yu-Chiuan; Hsiao, Chia-Chi; Chen, Po-Chou

    2017-03-01

    This study aimed to investigate the VX2 tumor growth in rabbit liver using T2-weighted imaging (T2WI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Five New Zealand white (NZW) rabbits were implanted with VX2 cell suspension in liver. Afterwards, MRI was performed 7, 14, 21 and 28 days after tumor implantation. A 1.5T clinical MRI scanner was used to perform scans. After 3-plane localizer, T1 weighted imaging (T1WI), T2WI, and DCE-MRI using a three-dimensional gradient echo pulse sequence was performed. After 4 pre-contrast images were acquired, each rabbit was injected i.v. with 0.1 mmol/kg Dotarem. The total scan time after Dotarem administration was 30 minutes. All acquired images were analyzed using ImageJ software. Several regions of interest were selected from the rims of tumor, liver, and muscle. The enhancement ratio (ER) was calculated by dividing the MR signal after Dotarem injection to the MR signal before Dotarem injection. The maximum ER (ER_max) value of tumor for each rabbit was observed right after the Dotarem injection. The T2W MR signal intensities (T2W_SI) and the ER_max values obtained 7, 14, 21 and 28 days after tumor implantation were analyzed with a linear regression algorithm. Both T2W_SI and ER_max of tumors increased with time. The changes for T2W_SI and ER_max of tumors between 7 and 28 days after tumor implantation were 32.66% and 18.14%, respectively. T2W_SI is more sensitive than ER_max for monitoring the growth of VX2 tumor in a rabbit liver model.

  15. Magnetic resonance imaging-navigated argon-helium cryoablation therapy against a rabbit VX2 brain tumor

    PubMed Central

    WANG, YANG; KAN, HONG-LI; SUN, HONG; WANG, DONG-XIN; WANG, HUAI-WU; LIU, JI-XIN

    2015-01-01

    The aim of the present study was to investigate the feasibility of interventional magnetic resonance imaging (MRI)-guided and monitored argon-helium cryoablation for the treatment of brain tumors in rabbits. In addition, the present study evaluated the associations between imaging and pathology, the therapeutic effects and the effects on the surrounding normal tissues. A total of 14 rabbits were equally divided into groups C and D. Under general anesthesia, the skull was drilled and tumor blocks were implanted. Subsequently, a New Zealand rabbit VX2 brain tumor model was successfully established. Rabbits in group C were treated with argon-helium cryoablation and those in group D did not undergo any treatment (control). Regular postoperative MRI scanning was performed to observe the changes in tumor size, and the survival times of the rabbits in groups C and D were recorded. The extent of necrosis in the brain tumor exhibited a significant correlation with the freezing time of cryoablation, and the necrotic region was shown to be the same size as the ice ball. The survival times of the rabbits in the treatment group (group C) were significantly prolonged. Therefore, the observations of the present study demonstrated that the VX2 brain tumor model, produced using an improved tumor block implantation method, was stable and suitable for MRI observation and interventional study. In addition, argon-helium cryoablation was shown to be a safe and feasible therapeutic method for the treatment of brain tumors, and was demonstrated to significantly increase the survival times of the brain tumor-bearing rabbits. PMID:26136965

  16. Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

    PubMed Central

    Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G; Vang, Russell; Cope, Leslie; Junge, Jette; Kjaer, Susanne K; Kurman, Robert J; Shih, Ie-Ming

    2014-01-01

    There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease identified from a nation-wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST–implant (non-invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non-invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour. PMID:24307542

  17. Combining dynamic contrast enhanced magnetic resonance imaging and microvessel density to assess the angiogenesis after PEI in a rabbit VX2 liver tumor model.

    PubMed

    Chen, Juan; Qian, Ting; Zhang, Huanhuan; Wei, Chunxiao; Meng, Fanhua; Yin, Huabin

    2016-02-01

    To evaluate the correlation between parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and microvessel density (MVD) measurements in rabbit VX2 liver tumor models after percutaneous ethanol injection (PEI) and to observe influence of PEI on angiogenesis in a rabbit VX2 liver tumor model with dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Forty five New Zealand white rabbits were used in this study. VX2 tumor tissue blocks were implanted in the left lobe of liver by percutaneous puncture under CT guidance. 2 weeks later, all rabbits underwent conventional MRI (T1WI, T2WI) to determine the successful models. Then those successful implanted VX2 liver tumor models in the study were randomly divided into the control group and the experimental group, the former did not have processing, and the latter underwent PEI under CT guidance. MRI (T1WI, T2WI and DCE-MRI) was performed 1 week later again, the parameters of DCE-MRI (Ktrans, Kep, Ve and iAUC60) of viable tumor portions were observed. Then all the liver samples were processed for hematoxylin and eosin (H&E) staining and immunohistochemical staining for CD31 to determine MVD. At last, data (including DCE-MRI perfusion parameters and MVD) were compared between experimental and control groups, correlation of DCE-MRI perfusion parameters and MVD was evaluated. Twenty six VX2 liver tumor models underwent all examinations (thirteen models for each group) 1 week later after PEI. For the experimental group, the parameters Ktrans (r=0.6382, P=0.0189) and iAUC60 (r=0.6591, P=0.0143) in viable tumor portions were positively moderately correlated with MVD, whereas the parameters Kep (r=0.4656, P=0.1088) and Ve (r=0.2918, P=0.3333) were not correlated with MVD. For the control group, the parameters Ktrans (r=0.6385, P=0.0188) and iAUC60 (r=0.6391, P=0.0187) in viable tumor portions were also positively moderately correlated with MVD, while the parameters Kep (r=0.5518, P=0.0506) and Ve (r

  18. 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

  19. The electronic structure and spin states of 2D graphene/VX2 (X = S, Se) heterostructures.

    PubMed

    Popov, Z I; Mikhaleva, N S; Visotin, M A; Kuzubov, A A; Entani, S; Naramoto, H; Sakai, S; Sorokin, P B; Avramov, P V

    2016-12-07

    The structural, magnetic and electronic properties of 2D VX2 (X = S, Se) monolayers and graphene/VX2 heterostructures were studied using a DFT+U approach. It was found that the stability of the 1T phases of VX2 monolayers is linked to strong electron correlation effects. The study of vertical junctions comprising of graphene and VX2 monolayers demonstrated that interlayer interactions lead to the formation of strong spin polarization of both graphene and VX2 fragments while preserving the linear dispersion of graphene-originated bands. It was found that the insertion of Mo atoms between the layers leads to n-doping of graphene with a selective transformation of graphene bands keeping the spin-down Dirac cone intact.

  20. Thermochemical Ablation Therapy of VX2 Tumor Using a Permeable Oil-Packed Liquid Alkali Metal

    PubMed Central

    Guo, Ziyi; Zhang, Qiang

    2015-01-01

    Objective Alkali metal appears to be a promising tool in thermochemical ablation, but, it requires additional data on safety is required. The objective of this study was to explore the effectiveness of permeable oil-packed liquid alkali metal in the thermochemical ablation of tumors. Methods Permeable oil-packed sodium–potassium (NaK) was prepared using ultrasonic mixing of different ratios of metal to oil. The thermal effect of the mixture during ablation of muscle tissue ex vivo was evaluated using the Fluke Ti400 Thermal Imager. The thermochemical effect of the NaK-oil mixture on VX2 tumors was evaluated by performing perfusion CT scans both before and after treatment in 10 VX2 rabbit model tumors. VX2 tumors were harvested from two rabbits immediately after treatment to assess their viability using trypan blue and hematoxylin and eosin (H.E.) staining. Results The injection of the NaK–oil mixture resulted in significantly higher heat in the ablation areas. The permeable oil controlled the rate of heat released during the NaK reaction with water in the living tissue. Perfusion computed tomography and its parameter map confirmed that the NaK–oil mixture had curative effects on VX2 tumors. Both trypan blue and H.E. staining showed partial necrosis of the VX2 tumors. Conclusions The NaK–oil mixture may be used successfully to ablate tumor tissue in vivo. With reference to the controlled thermal and chemical lethal injury to tumors, using a liquid alkali in ablation is potentially an effective and safe method to treat malignant tumors. PMID:25885926

  1. Thermochemical ablation therapy of VX2 tumor using a permeable oil-packed liquid alkali metal.

    PubMed

    Guo, Ziyi; Zhang, Qiang; Li, Xiaoguang; Jing, Zhengyu

    2015-01-01

    Alkali metal appears to be a promising tool in thermochemical ablation, but, it requires additional data on safety is required. The objective of this study was to explore the effectiveness of permeable oil-packed liquid alkali metal in the thermochemical ablation of tumors. Permeable oil-packed sodium-potassium (NaK) was prepared using ultrasonic mixing of different ratios of metal to oil. The thermal effect of the mixture during ablation of muscle tissue ex vivo was evaluated using the Fluke Ti400 Thermal Imager. The thermochemical effect of the NaK-oil mixture on VX2 tumors was evaluated by performing perfusion CT scans both before and after treatment in 10 VX2 rabbit model tumors. VX2 tumors were harvested from two rabbits immediately after treatment to assess their viability using trypan blue and hematoxylin and eosin (H.E.) staining. The injection of the NaK-oil mixture resulted in significantly higher heat in the ablation areas. The permeable oil controlled the rate of heat released during the NaK reaction with water in the living tissue. Perfusion computed tomography and its parameter map confirmed that the NaK-oil mixture had curative effects on VX2 tumors. Both trypan blue and H.E. staining showed partial necrosis of the VX2 tumors. The NaK-oil mixture may be used successfully to ablate tumor tissue in vivo. With reference to the controlled thermal and chemical lethal injury to tumors, using a liquid alkali in ablation is potentially an effective and safe method to treat malignant tumors.

  2. Arsenic trioxide treatment of rabbit liver VX-2 carcinoma via hepatic arterial cannulation-induced apoptosis and decreased levels of survivin in the tumor tissue

    PubMed Central

    Li, Hong; Gong, Jian; Jiang, Xuyuan; Shao, Haibo

    2013-01-01

    Aim To investigate the role of tumor apoptosis-inhibitory protein survivin in arsenic trioxide-induced apoptosis in VX-2 carcinoma in the rabbit liver by means of transcatheter arterial chemoembolization. Methods Sixteen rabbits with 32 implanted hepatic VX-2 tumors were randomly divided into two groups. The experimental group received 2 mg of arsenic trioxide and 1 mL of ultra-fluid lipiodol co-injected via hepatic arterial cannulation and the control group received only 1 mL of lipiodol. Animals were sacrificed 3 weeks after trans-catheterial arterial chemoembolization. Tumor tissue and tumor-peripheral tissue were collected for analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining was used to assess tumor cells apoptosis. Immunohistochemistry was used to assess the presence of survivin protein. Reverse transcription polymerase chain reaction was used to determine the expression of survivin gene. Results The number of apoptotic cells significantly increased in the tumor tissue (5.20 ± 0.60%) compared to tumor-peripheral tissue (1.29 ± 0.42%) of the arsenic trioxide-treated group. Survivin expression levels in the tumor tissue were significantly reduced in arsenic trioxide-treated group (7.68 ± 0.65) compared to the control group (35.30 ± 4.63). Conclusion Transcatheter arterial chemoembolization with arsenic trioxide induced apoptosis of VX-2 carcinoma, in which tumor apoptosis-inhibitory protein survivin may have played a role. PMID:23444241

  3. 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.

  4. Sentinel Node Mapping of VX2 Carcinoma in Rabbit Thigh with CT Lymphography Using Ethiodized Oil

    PubMed Central

    Lee, Yoon Jin; Lee, Kyoung Ho; Park, Ji Hoon; Lee, Hye Seung; Jung, Seung Chai; Joo, Seung-Moon

    2014-01-01

    Objective To assess the feasibility of computed tomography (CT) lymphography using ethiodized oil for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh. Materials and Methods This experiment received approval from the institutional animal use and care administrative advisory committee. Twenty-three rabbits with VX2 carcinoma in the thigh underwent CT before and after (1 hour, 2 hour) peritumoral injection of 2 mL ethiodized oil. After the CT examination, sentinel nodes were identified by peritumoral injection of methylene blue and subsequently removed. The retrieved sentinel and non-sentinel lymph nodes were investigated with radiographic and pathologic examinations. Based on the comparison of CT findings with those of radiographic and pathologic examinations, the diagnostic performance of CT for sentinel node identification was assessed. Results All 23 rabbits showed 53 ethiodized oil retention nodes on post-injection CT and specimen radiography, and 52 methylene blue-stained nodes at the right femoroiliac area. Of the 52 blue-stained sentinel nodes, 50 nodes demonstrated ethiodized oil retention. Thus, the sentinel node detection rate of CT was 96% (50 of 52). On pathologic examination, 28 sentinel nodes in 17 rabbits (nodes/rabbit, mean ± standard deviation, 1.7 ± 0.6) harbored metastasis. Twenty seven of the 28 metastatic sentinel nodes were found to have ethiodized oil retention. Conclusion Computed tomography lymphography using ethiodized oil may be feasible for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh. PMID:24497789

  5. Topical application of temoporfin-loaded invasomes for photodynamic therapy of subcutaneously implanted tumours in mice: a pilot study.

    PubMed

    Dragicevic-Curic, Nina; Gräfe, Susanna; Albrecht, Volker; Fahr, Alfred

    2008-04-25

    Temoporfin (mTHPC) represents a very potent second-generation synthetic photosensitizer. It has shown to be effective in the photodynamic therapy of early or recurrent oral carcinomas, in the palliative treatment of refractory oral carcinomas and in the treatment of primary non-melanomatous tumours of the skin of the head and neck. Until now for all positive findings an intravenous application of the photosensitizer was mandatory. In the case of cutaneous malignant or non-malignant diseases a topical application of the drug onto the site of the disease followed by illumination, would be advantageous. Unfortunately, mTHPC is a highly hydrophobic drug with a low percutaneous absorption. The purpose of this experiment was to investigate the photodynamic efficacy of novel mTHPC-loaded invasomes after their topical application onto the skin of mice bearing the subcutaneously implanted human colorectal tumour HT29 followed by photoirradiation. Invasomes are vesicles containing in addition to phospholipids a mixture of terpenes (cineole, citral and d-limonene) or only one terpene (citral) and ethanol, as penetration enhancers. This was a pilot study since until now no data are available about the efficacy of mTHPC in the photodynamic therapy of HT29 tumours after its topical application. The aim of this experiment was to investigate whether a mTHPC-loaded invasome formulation can reduce tumour size by photodynamic therapy or at least to find a formulation slowing down tumour growth compared to the control group (mice without any treatment). The groups of mice treated with mTHPC-invasomes containing 1% of the terpene mixture prior to photoirradiation showed a significantly smaller (p<0.05) tumour increase compared to control groups (mice without any treatment and mice only photoirradiated).

  6. 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).

  7. 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

  8. 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

  9. 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

  10. Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect.

    PubMed

    Kim, Gyoung Min; Kim, Man Deuk; Kim, Do Young; Kim, Se Hoon; Won, Jong Yun; Park, Sung Il; Lee, Do Yun; Shin, Wonseon; Shin, Minwoo

    2016-07-01

    To investigate feasibility, safety, and effect of transarterial chemoembolization using sorafenib on degree of tumor necrosis in a rabbit VX2 liver tumor model. New Zealand White rabbits (n = 20) with a VX2 tumor were divided into two groups; one group was treated with hepatic arterial administration of 0.5 mL ethiodized oil alone (Lipiodol; Guerbet, Aulnay-sous-Bois, France) (transarterial embolization with Lipiodol [TAE-L] group), and one group was treated with 0.5 mL ethiodized oil plus 10 mg sorafenib (transarterial embolization with sorafenib [TAE-S] group). Liquid chromatography tandem mass spectrometry was used to measure sorafenib concentration in peripheral blood and tissue. Hepatic enzymes, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1α (HIF-1α) were measured at 0, 24, and 72 hours after treatment. Histopathologic examination was performed to evaluate extent of tumor necrosis and normal parenchymal damage. Serum sorafenib concentration peaked at 2 hours after treatment. The mean tissue concentration was 406.8 times greater than the serum concentration. Aspartate aminotransferase and alanine aminotransferase levels were significantly elevated in the TAE-S group at 24 hours after treatment. Serum VEGF and HIF-1α concentrations were not significantly different between the TAE-L and TAE-S groups. Hepatic parenchymal damage was more severe in the TAE-S group. Mean fraction of tumor necrosis after treatment was significantly greater in the TAE-S group. Transarterial chemoembolization using sorafenib resulted in a high intrahepatic concentration of sorafenib. The degree of tumor necrosis was significantly greater in the TAE-S group compared with the TAE-L group, but more severe toxicity of normal liver tissue also occurred. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  11. Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model.

    PubMed

    Parvinian, Ahmad; Casadaban, Leigh C; Hauck, Zane Z; van Breemen, Richard B; Gaba, Ron C

    2015-01-01

    Use of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model. A 3 mg/kg dose of sorafenib ethiodized oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification. Sorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 μg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10-18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 μg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution. While targeted transarterial delivery of sorafenib ethiodized oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels.

  12. [Intravenous contrast-enhanced ultrasound of metastatic lymph nodes in rabbit VX2 tongue carcinoma model].

    PubMed

    Zhang, Yu; Shi, Fang; Li, Shi-min; Jin, Yun-jie; Wu, Hai-tao

    2012-06-01

    To investigate the sonographic features of the cervical lymph nodes in rabbit VX2 tongue carcinoma model and hyperplasia cervical lymph nodes model using gray scale contrast-enhanced ultrasonography (CEUS) after intravenous administration of SonoVue (a sonographic contrast agent) and to evaluate the potential utility of CEUS in detecting early metastatic cervical lymph nodes in the rabbit VX2 tongue carcinoma model. Twenty New Zealand rabbits were placed into 2 groups, 12 for node metastasis and 18 for node hyperplasia. Cervical CEUS was performed in the rabbits of both groups before and after intravenous administration of SonoVue(0.6 ml). The phase, pattern, beginning area and echogenicity of enhancement of the lymph nodes on the right neck were observed and recorded. Dissection of the lymph nodes were guided by the marks made during CEUS and examined histopathologically. On the right side of each rabbit only one lymph node were detected in both groups. All 8 cases in the hyperplasia group showed homogeneous enhancement starting from central, while in the metastasis group one case showed homogeneous enhancement starting from the central, 3 cases showed inhomogeneous enhancement starting from periphery, and 8 cases showed inhomogeneous enhancement starting both from central and periphery. One lymph node was dissected on the right side of the neck in each rabbit in both groups. Pathological examination showed all 12 lymph nodes in the metastatic group were metastatic lymph nodes, and all 8 lymph nodes in the hyperplasia group were hyperplastic lymph nodes. After intravenous CEUS, metastatic lymph nodes show inhomogeneous enhancement starting from periphery/central or periphery area, while hyperplastic lymph nodes show homogeneous enhancement starting from central area. Metastatic lymph nodes can be characterized as being neoplastic or benign on the basis of the enhancement patterns evaluated by CEUS.

  13. The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative analysis in rabbit VX2 liver cancer.

    PubMed

    Xiang, Zhiming; Liang, Qianwen; Liang, Changhong; Zhong, Guimian

    2014-12-01

    Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P < 0.01). The diagnostic results of CEUS and MRI perfusion quantitative analysis were not significantly different (P > 0.05). However, the quantitative parameter of them were significantly positively correlated (P < 0.05). CEUS and MRI perfusion quantitative analysis can both dynamically monitor the liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.

  14. 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

  15. 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.

  16. Optimal strategies for combining transcatheter arterial chemoembolization and radiofrequency ablation in rabbit VX2 hepatic tumors.

    PubMed

    Mostafa, Elian M; Ganguli, Suvranu; Faintuch, Salomao; Mertyna, Pawel; Goldberg, S Nahum

    2008-12-01

    To determine the optimum combination strategy of transcatheter arterial chemoembolization and radiofrequency (RF) ablation in an experimentally induced hepatic tumor model. Twenty-five New Zealand White rabbits with VX2 carcinoma-induced hepatic tumors were randomly divided into five treatment groups, which received (i) chemoembolization followed 15 minutes later by RF ablation; (ii) RF ablation followed by chemoembolization; (iii) chemoembolization alone; (iv) RF ablation alone; and (v) bland embolization followed by RF ablation. Animals were euthanized at 48 hours to determine tumor infarction and coagulation, which were compared with analysis of variance. Representative histopathologic slides were compared. Significantly larger areas of coagulation were produced by chemoembolization followed by RF ablation (22.0 cm(3) +/- 7.7) compared with RF ablation followed by chemoembolization (13.1 cm(3) +/- 3.2) and RF ablation alone (10.0 cm(3) +/- 4.5; P < .05). RF ablation followed by chemoembolization showed larger treatment areas than chemoembolization alone (25.0 cm(3) +/- 9.6 vs 12.1 cm(3) +/- 4.6; P < .001), with chemotherapeutic agent preferentially depositing around the coagulation zone. Histopathologic analysis revealed greater vascular thrombosis and necrosis and reduced islands of viable tumor cells in the chemoembolization/RF ablation group versus the groups treated with chemoembolization alone or bland embolization/RF ablation. Larger treatment volumes were produced when chemoembolization was performed before RF ablation than when RF ablation preceded chemoembolization or when RF ablation or chemoembolization were performed alone. Larger treatment volumes were also produced when chemoembolization rather than bland embolization was performed before RF ablation, indicating the importance and synergy of the chemotherapeutic regimen. These results suggest that the reduction of tumor blood flow combined with the effect of hyperthermia and local chemotherapy

  17. Tumour bed delineation for partial breast/breast boost radiotherapy: what is the optimal number of implanted markers?

    PubMed

    Kirby, Anna Nm; Jena, Rajesh; Harris, Emma J; Evans, Phil M; Crowley, Clare; Gregory, Deborah L; Coles, Charlotte E

    2013-02-01

    International consensus has not been reached regarding the optimal number of implanted tumour bed (TB) markers for partial breast/breast boost radiotherapy target volume delineation. Four common methods are: insertion of 6 clips (4 radial, 1 deep and 1 superficial), 5 clips (4 radial and 1 deep), 1 clip at the chest wall, and no clips. We compared TB volumes delineated using 6, 5, 1 and 0 clips in women who have undergone wide-local excision (WLE) of breast cancer (BC) with full-thickness closure of the excision cavity, in order to determine the additional margin required for breast boost or partial breast irradiation (PBI) when fewer than 6 clips are used. Ten patients with invasive ductal BC who had undergone WLE followed by implantation of six fiducial markers (titanium clips) each underwent CT imaging for radiotherapy planning purposes. Retrospective processing of the DICOM image datasets was performed to remove markers and associated imaging artefacts, using an in-house software algorithm. Four observers outlined TB volumes on four different datasets for each case: (1) all markers present (CT6M); (2) the superficial marker removed (CT(5M)); (3) all but the chest wall marker removed (CTCW); (4) all markers removed (CT(0M)). For each observer, the additional margin required around each of TB(0M), TBCW, and TB(5M) in order to encompass TB(6M) was calculated. The conformity level index (CLI) and differences in centre-of-mass (COM) between observers were quantified for CT(0M), CTCW, CT(5M), CT(6M). The overall median additional margins required to encompass TB(6M) were 8mm (range 0-28 mm) for TB(0M), 5mm (range 1-13 mm) for TBCW, and 2mm (range 0-7 mm) for TB(5M). CLI were higher for TB volumes delineated using CT(6M) (0.31) CT(5M) (0.32) than for CTCW (0.19) and CT(0M) (0.15). In women who have undergone WLE of breast cancer with full-thickness closure of the excision cavity and who are proceeding to PBI or breast boost RT, target volume delineation based on 0 or

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Distal femur reconstruction with modular tumour prostheses: a single Institution analysis of implant survival comparing fixed versus rotating hinge knee prostheses.

    PubMed

    Pala, Elisa; Trovarelli, Giulia; Angelini, Andrea; Ruggieri, Pietro

    2016-10-01

    To evaluate the incidence of complications in distal femur reconstructions with modular prostheses, comparing fixed vs rotating hinge knee. Retrospective analysis of implant survival, complications, and functional results of the Rizzoli series on distal femur megaprosthesis. Between 1983 and 2010, 687 distal femur tumour modular prostheses were implanted: 491 fixed hinge and 196 rotating hinge knee prostheses. Failures of the prostheses were classified in five types: type 1, soft tissue failure; type 2, aseptic loosening; type 3, structural failure; type 4, infection; type 5, tumour progression. Failure rate was 27 % (185/687). Implant survival to all types of failure was 70 % at ten years and 50 % at 20 years with no significant difference between fixed and rotating hinge knee prostheses (p = 0.0928). When excluding type 5 and type 1 failures, the overall survival was 78 % and 58 % at ten and 20 years. There was not a significant difference in implant survival to aseptic loosening (p = 0.5) and infection (p = 0.2) between fixed and rotating hinge knee prostheses. All cases of breakage of prosthetic components occurred in fixed hinge knee prostheses. Functional results, evaluated in 536 pts, were satisfactory in 91.4 % of cases with a mean score of 23.3 with a significantly better function for rotating hinge knee prostheses (p < 0.001). The most frequent cause of failure was infection followed by aseptic loosening. Even if better results were expected for rotating hinge knee prostheses, there is no significant difference in overall implant survival. No cases of breakage of prosthetic components occurred in rotating hinge knee prosthesis. Functional results were significantly better for the rotating hinge knee prostheses. Therapeutic study, level IV (case series).

  4. Phase stability of the nanolaminates V2Ga2C and (Mo1-xVx)2Ga2C from first-principles calculations.

    PubMed

    Thore, A; Dahlqvist, M; Alling, B; Rosen, J

    2016-05-14

    We here use first-principles calculations to investigate the phase stability of the hypothetical laminated material V2Ga2C and the related alloy (Mo1-xVx)2Ga2C, the latter for a potential parent material for synthesis of (Mo1-xVx)2C, a new two-dimensional material in the family of so called MXenes. We predict that V2Ga2C is thermodynamically stable with respect to all identified competing phases in the ternary V-Ga-C phase diagram. We further calculate the stability of ordered and disordered configurations of Mo and V in (Mo1-xVx)2Ga2C and predict that ordered (Mo1-xVx)2Ga2C for x≤ 0.25 is stable, with an order-disorder transition temperature of ∼1000 K. Furthermore, (Mo1-xVx)2Ga2C for x = 0.5 and x≥ 0.75 is suggested to be stable, but only for disordered Mo-V configurations, and only at elevated temperatures. We have also investigated the electronic and elastic properties of V2Ga2C; the calculated bulk, shear, and Young's modulus are 141, 94, and 230 GPa, respectively.

  5. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel alpha(nu)beta3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging.

    PubMed

    Winter, Patrick M; Caruthers, Shelton D; Kassner, Andrea; Harris, Thomas D; Chinen, Lori K; Allen, John S; Lacy, Elizabeth K; Zhang, Huiying; Robertson, J David; Wickline, Samuel A; Lanza, Gregory M

    2003-09-15

    Early noninvasive detection and characterization of solid tumors and their supporting neovasculature is a fundamental prerequisite for effective therapeutic intervention, particularly antiangiogenic treatment regimens. Emerging molecular imaging techniques now allow recognition of early biochemical, physiological, and anatomical changes before manifestation of gross pathological changes. Although new tumor, vascular, extracellular matrix, and lymphatic biomarkers continue to be discovered, the alpha(nu)beta(3)-integrin remains an attractive biochemical epitope that is highly expressed on activated neovascular endothelial cells and essentially absent on mature quiescent cells. In this study, we report the first in vivo use of a magnetic resonance (MR) molecular imaging nanoparticle to sensitively detect and spatially characterize neovascularity induced by implantation of the rabbit Vx-2 tumor using a common clinical field strength (1.5T). New Zealand White rabbits (2 kg) 12 days after implantation of fresh Vx-2 tumors (2 x 2 x 2 mm(3)) were randomized into one of three treatment groups: (a) alpha(nu)beta(3)-targeted, paramagnetic formulation; (b) nontargeted, paramagnetic formulation; and (c) alpha(nu)beta(3)-targeted nonparamagnetic nanoparticles followed by (2 h) the alpha(nu)beta(3)-targeted, paramagnetic formulation to competitively block magnetic resonance imaging (MRI) signal enhancement. After i.v. systemic injection (0.5 ml of nanoparticles/kg), dynamic T(1)-weighted MRI was used to spatially and temporally determine nanoparticle deposition in the tumor and adjacent tissues, including skeletal muscle. At 2-h postinjection, alpha(nu)beta(3)-targeted paramagnetic nanoparticles increased MRI signal by 126% in asymmetrically distributed regions primarily in the periphery of the tumor. Similar increases in MR contrast were also observed within the walls of some vessels proximate to the tumor. Despite their relatively large size, nanoparticles penetrated into the

  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. 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.

  8. Assessment of tumor angiogenesis: dynamic contrast-enhanced MRI with paramagnetic nanoparticles compared with Gd-DTPA in a rabbit Vx-2 tumor model.

    PubMed

    Kassner, Andrea; Thornhill, Rebecca E; Liu, Fang; Winter, Patrick M; Caruthers, Shelton D; Wickline, Samuel A; Lanza, Gregory M

    2010-01-01

    The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd-DTPA) using dynamic contrast-enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12-14 days after Vx-2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd-DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (K(i)) maps were calculated using a two-compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The K(i) values estimated using PNs were significantly lower than those obtained for Gd-DTPA (p = 0.018). When PNs and Gd-DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd-DTPA data (p = 0.34). The mean K(i) for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd-DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd-DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis.

  9. Monoclonal antibody Po66 uptake by human lung tumours implanted in nude mice: effect of co-administration with doxorubicin.

    PubMed Central

    Desrues, B.; Léna, H.; Brichory, F.; Ramée, M. P.; Toujas, L.; Delaval, P.; Dazord, L.

    1995-01-01

    The efficacy of radioimmunotherapy of tumours with radiolabelled monoclonal antibodies (MAbs) depends on the amount of antibody taken up by the tumour and on its intratumoral distribution. In the case of MAbs directed against intracellular antigens, increasing the permeability of the cytoplasmic membrane may augment the bioavailability of the antigen for the antibody. This raises the question whether the induction of tumour necrosis by chemotherapy can enhance the tumour uptake of radiolabelled monoclonal antibodies. In this work, the effect of doxorubicin on the biodistribution of Po66, an MAb directed against an intracellular antigen, was studied in nude mice grafted with the human non-small-cell lung carcinoma cell line SK-MES-1. After injection on day 0 of 125I-labelled Po66, tumour radioactivity increased up to days 3-5, and then remained unchanged to day 14. The combined administration of 125I-labelled Po66 with 8 mg kg-1 doxorubicin, in two doses separated by 7 days, doubled the radioactivity retained by the tumour. Histological and historadiographic analysis showed, however, that the drug induced cellular damage. In the absence of doxorubicin, the accumulation of Po66 was restricted to some necrotic areas, whereas with doxorubicin the necrosis was more extensive and the antibody more evenly distributed. These results suggest that chemotherapy and immunoradiotherapy combined would enhance tumour uptake of radioisotope and promote more homogenous distribution of the radiolabelled MAb. This would promote eradication of the remaining drug-resistant cells in tumours. Images Figure 2 Figure 5 PMID:7577450

  10. Re-implantation of cryopreserved ovarian cortex resulting in restoration of ovarian function, natural conception and successful pregnancy after haematopoietic stem cell transplantation for Wilms tumour.

    PubMed

    Dunlop, C E; Brady, B M; McLaughlin, M; Telfer, E E; White, J; Cowie, F; Zahra, S; Wallace, W H B; Anderson, R A

    2016-12-01

    With the improvement of long-term cancer survival rates, growing numbers of female survivors are suffering from treatment-related premature ovarian insufficiency (POI). Although pre-treatment embryo and oocyte storage are effective fertility preservation strategies, they are not possible for pre-pubertal girls or women who cannot delay treatment. In these cases, the only available treatment option is ovarian cortex cryopreservation and subsequent re-implantation. A 32-year-old woman had ovarian cortex cryopreserved 10 years previously before commencing high-dose chemotherapy and undergoing a haematopoietic stem cell transplant for recurrent adult Wilms tumour, which resulted in POI. She underwent laparoscopic orthotopic transplantation of cryopreserved ovarian cortex to the original site of biopsy on the left ovary. She ovulated at 15 and 29 weeks post-re-implantation with AMH detectable, then rising, from 21 weeks, and conceived naturally following the second ovulation. The pregnancy was uncomplicated and a healthy male infant was born by elective Caesarean section at 36(+4) weeks gestation. This is the first report of ovarian cortex re-implantation in the UK. Despite the patient receiving low-risk chemotherapy prior to cryopreservation and the prolonged tissue storage duration, the re-implantation resulted in rapid restoration of ovarian function and natural conception with successful pregnancy.

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

    PubMed Central

    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.

    2016-01-01

    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

  12. Multimodal imaging using optical coherence tomography and endolaryngeal ultrasonography in a new rabbit VX2 laryngeal cancer model.

    PubMed

    Oak, Chulho; Ahn, Yeh-Chan; Nam, Sung-Jin; Jung, Maan Hong; Hwang, Sang Seok; Chae, Yu-Gyeong; Lee, Hyoung Shin; Lee, Kang Dae; Jung, Min Jung; Chun, Bong Kwon; Lee, Hae Young; Park, Eun-Kee; Kim, Sung Won

    2015-11-01

    Optical coherence tomography (OCT) provides ultrahigh-resolution imaging of tissues within a depth of a few millimeters, whereas ultrasonography provides good imaging further below the surface. We aimed to develop a minimally invasive rabbit model of VX2 laryngeal cancer, suitable for these two imaging modalities through a transoral approach. We also sought to study the utility of combined OCT and endolaryngeal ultrasonography (EUS) for evaluation of early and advanced laryngeal cancer, using this model. VX2 tumor suspension was inoculated into the vocal folds of ten rabbits by injection through the trans-thyrohyoid membrane. The tumor model was characterized by rigid laryngoscopy and the tumor generation rate was 80% (8/10). Correlation between frequency-domain OCT and high-frequency EUS were used to visualize laryngeal tumors in the area of protruding mass formation in four rabbits, one week after injection (group A) and the remaining four rabbits two weeks after injection (group B). A small submucosal tumor was observed with rigid laryngoscopy in group A, and pathologic evaluation showed that the tumor was close to the basement membrane of the vocal fold mucosa, but had not invaded. OCT confirmed that the lining of the mucosa and basement membrane of the vocal fold was not broken, but the mucosa had thinned at the most elevated ridge. However, these lesions were not detected by EUS, and the overall shape of the tumor could not be clearly identified by EUS. A large tumor filling the laryngeal lumen was observed with rigid laryngoscopy in group B, and nearly the entire vocal fold, including the paraglottic space, was found to be involved on pathologic analysis. Distinguishing between normal structures and tumor was difficult using OCT; however, EUS confirmed the overall shape, size, and extent of the tumor, and the paraglottic space and thyroid cartilage were shown to be intact. This study is the first experimental trial, assessing the value of multimodal imaging

  13. 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

  14. 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.

  15. Distribution of Iron Oxide Core-Titanium Dioxide Shell Nanoparticles in VX2 Tumor Bearing Rabbits Introduced by Two Different Delivery Modalities

    SciTech Connect

    Refaat, Tamer; West, Derek; El Achy, Samar; Parimi, Vamsi; May, Jasmine; Xin, Lun; Harris, Kathleen; Liu, William; Wanzer, Michael; Finney, Lydia; Maxey, Evan; Vogt, Stefan; Omary, Reed; Procissi, Daniele; Larson, Andrew; Paunesku, Tatjana; Woloschak, Gayle

    2016-08-03

    This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. This difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.

  16. Distribution of Iron Oxide Core-Titanium Dioxide Shell Nanoparticles in VX2 Tumor Bearing Rabbits Introduced by Two Different Delivery Modalities

    PubMed Central

    Refaat, Tamer; West, Derek; El Achy, Samar; Parimi, Vamsi; May, Jasmine; Xin, Lun; Harris, Kathleen R.; Liu, William; Wanzer, Michael Beau; Finney, Lydia; Maxey, Evan; Vogt, Stefan; Omary, Reed A.; Procissi, Daniele; Larson, Andrew C.; Paunesku, Tatjana; Woloschak, Gayle E.

    2016-01-01

    This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. This difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future. PMID:28335271

  17. Distribution of iron oxide core-titanium dioxide shell nanoparticles in VX2 tumor bearing rabbits introduced by two different delivery modalities

    DOE PAGES

    Refaat, Tamer; West, Derek; El Achy, Samar; ...

    2016-08-03

    This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Bothmore » IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. Furthermore, this difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.« less

  18. Distribution of iron oxide core-titanium dioxide shell nanoparticles in VX2 tumor bearing rabbits introduced by two different delivery modalities

    SciTech Connect

    Refaat, Tamer; West, Derek; El Achy, Samar; Parimi, Vamsi; May, Jasmine; Xin, Lun; Harris, Kathleen R.; Liu, William; Wanzer, Michael Beau; Finney, Lydia; Maxey, Evan; Vogt, Stefan; Omary, Reed A.; Procissi, Daniele; Larson, Andrew C.; Paunesku, Tatjana; Woloschak, Gayle E.

    2016-08-03

    This work compares intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core-titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits. NPs coated with glucose and decorated with a peptide sequence from cortactin were administered to animals with developed VX2 liver cancer. Two hours after NPs delivery tumors, normal liver, kidney, lung and spleen tissues were harvested and used for a series on histological and elemental analysis tests. Quantification of NPs in tissues was done both by bulk inductively coupled plasma mass spectrometry (ICP-MS) analysis and by hard X-ray fluorescence microscopy. Both IV and IC NPs injection are feasible modalities for delivering NPs to VX2 liver tumors with comparable tumor accumulation. It is possible that this is an outcome of the fact that VX2 tumors are highly vascularized and hemorrhagic, and therefore enhanced permeability and retention (EPR) plays the most significant role in accumulation of nanoparticles in tumor tissue. It is, however, interesting to note that IV delivery led to increased sequestration of NPs by spleen and normal liver tissue, while IC delivery lead to more NP positive Kupffer cells. Furthermore, this difference is most likely a direct outcome of blood flow dynamics. Armed with this knowledge about nanoparticle delivery, we plan to test them as radiosensitizers in the future.

  19. [Non-thermal effect of high-intensity focused ultrasound on ultrastructure and apoptosis in rabbit hepatic VX2 tumors].

    PubMed

    Peng, Song; He, Wei

    2015-07-01

    目的:观察高强度聚焦超声(high-intensity focused ultrasound,HIFU)热效应和非热效应损伤后兔肝VX2肿瘤的微观形态学变化。方法:将40只兔肝VX2肿瘤模型大白兔随机分为热效应组(n=20)和非热效应组(n=20),每组于治疗后即刻及3,7,14 d分别随机处死5只,分析超微结构、凋亡相关蛋白表达及细胞凋亡情况。结果:电镜显示HIFU辐照后各时间点非热效应组的组织细胞破坏程度较热效应组严重。消融后两组交界区凋亡相关蛋白即刻及3 d血管内皮生长因子(vascular endothelial growth factor,VEGF)呈低水平表达,7~14 d均逐渐升高,各时间点两组相比差异均无统计学意义(均P>0.05);caspase-3治疗后3 d表达达到高峰,3与7 d时非热效应组表达明显高于热效应组(均P<0.05);NF-κB的表达3 d时开始增加,7 d达高峰,14 d开始下降,各时间点两组相比差异无统计学意义(均P>0.05)。TUNEL检测HIFU治疗后交界区凋亡阳性细胞,发现3与7 d非热效应组高于热效应组(均P<0.01),凋亡指数分别为(28.60±1.14)%,(21.80±1.92)%和(21.00±1.58)%,(14.80±1.48)%。结论:HIFU热效应及非热效应机制均能诱导交界区凋亡产生,而后者效果更为强烈。.

  20. Targeting of VX2 rabbit liver tumor by selective delivery of 3-bromopyruvate: a biodistribution and survival study.

    PubMed

    Vali, Mustafa; Vossen, Josephina A; Buijs, Manon; Engles, James M; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Ganapathy-Kanniappan, Shanmugasundaram; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L; Geschwind, Jean-Francois H

    2008-10-01

    The aim of this study was to determine the biodistribution and tumor targeting ability of (14)C-labeled 3-bromopyruvate ([(14)C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [(14)C]3-BrPA on tumor and healthy tissue glucose metabolism by determining (18)F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [(14)C]3-BrPA i.a., 1.75 mM [(14)C]3-BrPA i.v., 20 mM [(14)C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [(14)C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [(14)C]3-BrPA was 1.8 +/- 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [(14)C]3-BrPA was 0.03 +/- 0.01% ID/g. After i.a. administration of [(14)C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [(14)C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit.

  1. Treatment of (131)I-labeled anti-CD147 monoclonal antibody in VX2 carcinoma-induced liver tumors.

    PubMed

    Niu, Huanzhang; Wang, Ruihua; Cheng, Jingliang; Gao, Shegan; Liu, Baoping

    2013-07-01

    Hepatocellular carcinoma (HCC) is a major health problem worldwide. CD147 has been reported to be overexpressed in HCC and blocking CD147 expression can decrease tumor growth. (131)I is often used in combination with other drugs to treat HCC and yields positive results. In this study, we combined the (131)I and CD147 monoclonal antibody to treat HCC in a rabbit VX2 animal model. In the (131)I-labeled CD147 antibody ((131)I-CD147-Ab) treatment group, the animals lived considerably longer than the animals in the other treatment groups. Metastasis and tumor growth in the (131)I-CD147-Ab treatment group were also inhibited. MMP2 and CD31 expression were significantly lower in the treatment group, whereas Tunel staining was overexpressed. These findings suggest that (131)I-CD147-Ab is a promising drug in the treatment of HCC, by inhibiting metastasis and growth and by decreasing the expression of MMP2 and CD31 or by inducing tumor necrosis. After testing the biochemical parameters, (131)I-CD147-Ab caused fewer side-effects in the animals.

  2. 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

  3. 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

  4. 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.

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

    PubMed Central

    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

    2016-01-01

    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

  6. 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

  7. 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.

  8. Liver Injury and Tumor-Inhibiting Effect of Sequential Transcatheter Arterial Chemoembolization and Portal Venous Embolization on Rabbit VX2 Liver Carcinoma

    PubMed Central

    Song, Dongda; Hu, Minggen; Guo, Weichang

    2017-01-01

    Background The concepts of sequential transcatheter arterial chemoembolization (TACE) and portal venous embolization (PVE) were proposed to prevent the detrimental tumor growth-inducing effect of PVE and to facilitate growth of further future liver remnant (FLR). This study aimed to investigate the effect of sequential TACE and PVE on liver damage and the therapeutic effect in a rabbit VX2 liver tumor model. Material/Methods Rabbits bearing VX2 liver tumors were randomly divided into TACE+PVE, TACE, PVE, and Sham groups. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and alkaline phosphatase (ALP) at 6 h, 24 h, 3 days, and 7 days were measured by ELISA assay. Tumor diameter on day 7 was measured and the tumor sections with cleaved caspase-3 was stained and observed. Results Plasma ALT, AST, and ALP levels were significantly increased at the first hours after the interventions. The TACE group had higher increases than the TACE+PVE and PVE alone groups. ALT, AST, and ALP levels decreased on day 7 and presented a trend to return to the baseline level. The TACE+PVE group showed stronger tumor-inhibiting effect than the TACE and PVE alone groups and also induced the highest level of tumor cell apoptosis. Conclusions The liver damage caused by TACE+PVE is mild and recoverable. TACE+PVE showed stronger tumor-inhibiting effect than in the TACE and PVE group and also induced the highest level of tumor cell apoptosis. PMID:28344313

  9. Liver Injury and Tumor-Inhibiting Effect of Sequential Transcatheter Arterial Chemoembolization and Portal Venous Embolization on Rabbit VX2 Liver Carcinoma.

    PubMed

    Song, Dongda; Hu, Minggen; Guo, Weichang

    2017-03-27

    BACKGROUND The concepts of sequential transcatheter arterial chemoembolization (TACE) and portal venous embolization (PVE) were proposed to prevent the detrimental tumor growth-inducing effect of PVE and to facilitate growth of further future liver remnant (FLR). This study aimed to investigate the effect of sequential TACE and PVE on liver damage and the therapeutic effect in a rabbit VX2 liver tumor model. MATERIAL AND METHODS Rabbits bearing VX2 liver tumors were randomly divided into TACE+PVE, TACE, PVE, and Sham groups. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and alkaline phosphatase (ALP) at 6 h, 24 h, 3 days, and 7 days were measured by ELISA assay. Tumor diameter on day 7 was measured and the tumor sections with cleaved caspase-3 was stained and observed. RESULTS Plasma ALT, AST, and ALP levels were significantly increased at the first hours after the interventions. The TACE group had higher increases than the TACE+PVE and PVE alone groups. ALT, AST, and ALP levels decreased on day 7 and presented a trend to return to the baseline level. The TACE+PVE group showed stronger tumor-inhibiting effect than the TACE and PVE alone groups and also induced the highest level of tumor cell apoptosis. CONCLUSIONS The liver damage caused by TACE+PVE is mild and recoverable. TACE+PVE showed stronger tumor-inhibiting effect than in the TACE and PVE group and also induced the highest level of tumor cell apoptosis.

  10. 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.

  11. 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

  12. 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.

  13. Evaluation of Chemotherapy Response in VX2 Rabbit Lung Cancer with 18F-Labeled C2A Domain of Synaptotagmin I

    PubMed Central

    Wang, Feng; Fang, Wei; Zhang, Ming-Rong; Zhao, Ming; Liu, Biao; Wang, Zizheng; Hua, Zichun; Yang, Min; Kumata, Katsushi; Hatori, Akiko; Yamasaki, Tomoteru; Yanamoto, Kazuhiko; Suzuki, Kazutoshi

    2013-01-01

    The C2A domain of synaptotagmin I can target apoptotic cells by binding to exposed anionic phospholipids. The goal of this study was to synthesize and develop 18F-labeled C2A-gluta-thione-S-transferase (GST) as a molecular imaging probe for the detection of apoptosis and to assess the response of paclitaxel chemotherapy in VX2 rabbit lung cancer. Methods 18F-C2A-GST was prepared by labeling C2A-GST with N-succinimidyl 4-18F-fluorobenzoate (18F-SFB). 18F-C2A-GST was confirmed by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The binding of 18F-C2A-GST toward apoptosis was validated in vitro using camptothecin-induced Jurkat cells. Biodistribution of 18F-C2A-GST was determined in mice by a dissection method and small-animal PET. Single-dose paclitaxel was used to induce apoptosis in rabbits bearing VX2 tumors (n = 6), and 2 VX2 rabbits without treatment served as control. 18F-C2A-GST PET was performed before and at 72 h after therapy, and 18F-FDG PET/CT was also performed before treatment. To confirm the presence of apoptosis, tumor tissue was analyzed and activated caspase-3 was measured. Results 18F-C2A-GST was obtained with more than 95% radiochemical purity and was stable for 4 h after formulation. 18F-C2A-GST bound apoptotic cells specifically. Biodistribution in mice showed that 18F-C2A-GST mainly excreted from the kidneys and rapidly cleared from blood and nonspecific organs. High focal uptake of 18F-C2A-GST in the tumor area was determined after therapy, whereas no significant uptake before therapy was found in the tumor with 18F-FDG–avid foci. The maximum standardized uptake value after therapy was 0.47 ± 0.28, significantly higher than that in the control (0.009 ± 0.001; P < 0.001). The apoptotic index was 79.81% ± 8.73% in the therapy group, significantly higher than that in the control (5.03% ± 0.81%; P < 0.001). Activated caspase-3 after paclitaxel treatment increased to 69.55% ± 16.27% and

  14. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Ablation of high-intensity focused ultrasound assisted with SonoVue on Rabbit VX2 liver tumors: sequential findings with histopathology, immunohistochemistry, and enzyme histochemistry.

    PubMed

    Luo, Wen; Zhou, Xiaodong; Yu, Ming; He, Guangbin; Zheng, Xiaoying; Li, Qiuyang; Liu, Qing; Han, Zenghui; Zhang, Jun; Qian, Yunqiu

    2009-08-01

    We investigated sequential effects of HIFU ablation combined with contrast agent SonoVue by using histopathology examination, immunohistochemistry, and enzyme histochemistry. Forty rabbits with VX2 liver tumors were subjected to HIFU ablation. Before ablation, a bolus injection of 0.2 mL SonoVue was administrated in group II (n = 20), and normal saline solution was injected in group I (n = 20). On day 0, 3, 7, and 14 after ablation, 5 animals in each group were sacrificed. The tissue in ablated zone, transient zone (within 3 mm around ablated area), and surrounding zone (beyond 3 mm around ablated area) were collected. Coagulated volume measurement, hematoxylin-eosin staining, immunohistochemistry of Ki 67, Bcl-2, CD54, and MMP-2 to determine cell proliferation and tissue repair, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and succinic dehydrogenase (SDH) staining to evaluate tissue viability were performed. The coagulated volume in group II at each time point was larger than that in group I (P < .05). After day 3, hematoxylin-eosin staining demonstrated necrosis in ablated zones and increasing surrounding fibra bands in group I and group II, while increasing expression of Ki 67, Bcl-2, CD54, and MMP-2 in transient zones was detected using immunohistochemistry in both groups (P > .05). NADPH-d and SDH staining showed dramatic decrease of enzyme activities in ablated zones immediately after ablation, while residual viable tissues in ablated zones of group II were less than those of group I (P < .05). Contrast agent SonoVue enables improvement of HIFU ablation on rabbit VX2 liver tumors.

  16. Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model

    PubMed Central

    Ranjan, Ashish; Jacobs, Genevieve; Woods, David L.; Negussie, Ayele H.; Partanen, Ari; Yarmolenko, Pavel S.; Gacchina, Carmen E.; Sharma, Karun V.; Frenkel, Victor; Wood, Bradford J.; Dreher, Matthew R.

    2012-01-01

    Clinical-grade Doxorubicin encapsulated low temperature sensitive liposomes (LTSLs) were combined with a clinical magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) platform to investigate in-vivo image-guided drug delivery. Plasma pharmacokinetics were determined in 3 rabbits. Fifteen rabbits with Vx2 tumors within superficial thigh muscle were randomly assigned into three treatment groups: 1) free doxorubicin, 2) LTSL and 3) LTSL+MR-HIFU. For the LTSL+MR-HIFU group, mild hyperthermia (40–41°C) was applied to the tumors using an MR-HIFU system. Image-guided non-invasive hyperthermia was applied for a total of 30 min, completed within 1 hour after LTSL infusion. High-pressure liquid chromatography (HPLC) analysis of the harvested tumor and organ/tissue homogenates was performed to determine doxorubicin concentration. Fluorescence microscopy was performed to determine doxorubicin spatial distribution in the tumors. Sonication of Vx2 tumors resulted in accurate (mean=40.5±0.1°C) and spatially homogenous (SD=1.0°C) temperature control in the target region. LTSL+MR-HIFU resulted in significantly higher tumor doxorubicin concentrations (7.6- and 3.4-fold greater compared to free doxorubicin and LTSL respectively, p<0.05, Newman-Keuls). This improved tumor concentration was achieved despite heating <25% of the tumor volume. Free doxorubicin and LTSL treatments appeared to deliver more drug in the tumor periphery as compared to the tumor core. In contrast, LTSL+MR-HIFU treatment suggested an improved distribution with doxorubicin found in both the tumor periphery and core. Doxorubicin bio-distribution in non-tumor organs/tissues was fairly similar between treatment groups. This technique has potential for clinical translation as an image-guided method to deliver drug to a solid tumor. PMID:22210162

  17. Resistance to tumour challenge after tumour laser thermotherapy is associated with a cellular immune response

    PubMed Central

    Ivarsson, K; Myllymäki, L; Jansner, K; Stenram, U; Tranberg, K-G

    2005-01-01

    Previous studies in our laboratory have shown that interstitial laser thermotherapy (ILT) of an experimental liver tumour is superior to surgical excision, at least partly due to a laser-induced immunological effect. The aim of the present study was to investigate the time–response relationship of the ILT-induced immunisation and the cellular response of macrophages and lymphocytes. A dimethylhydrazine-induced adenocarcinoma was transplanted into the liver of syngeneic rats. Rats with tumour were treated 6–8 days later (tumour size 0.25–0.40 cm3) with ILT of tumour or resection of the tumour-bearing lobe. Two groups of rats without tumour were treated with resection of a normal liver lobe or ILT of normal liver. A challenging tumour was implanted into the liver of each rat 2, 5 or 10 weeks after primary treatment. Rats were killed 6, 12 and 48 days (or earlier due to their condition) after challenge (n=8 in all groups). Immunohistochemical techniques were used to determine lymphocytes (CD8, CD4) and macrophages (ED1, ED2) in rats having had treatment of a primary tumour. Interstitial laser thermotherapy of the first tumour was followed by eradication of challenging tumour and absence of tumour spread. This contrasted with rapid growth and spread of challenging tumour in the other groups. In the challenging vital tumour tissue and in the interface between the tumour and surroundings, the number of ED1 macrophages and CD8 lymphocytes was higher in rats having been treated with the ILT of tumour than in those having undergone resection of the tumour-bearing lobe. The number of ED2 macrophages and CD4 lymphocytes was low and did not vary between these two groups. Interstitial laser thermotherapy elicited an immune response that eradicated a challenging tumour and was associated with increased numbers of tumour-infiltrating macrophages and CD8 lymphocytes. PMID:16091763

  18. Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors.

    PubMed

    Huang, Lili; Shen, Ming; Li, Rongxin; Zhang, Xiangyu; Sun, Ying; Gao, Pei; Fu, Hao; Liu, Hongqiang; He, Yang; Du, Yuqing; Cao, Jun; Duan, Yourong

    2016-11-08

    Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy.

  19. Detection and Pathologic Evaluation of Sentinel Lymph Nodes in the VX2 Tumor Model Using a Novel Ultrasound/Near-Infrared Dual-Modality Contrast Agent.

    PubMed

    Qu, Enze; Dai, Zhifei; Liang, Xiaolong; Qian, Yajun; Wang, Shumin; Ke, Hengte; Wang, Jinrui

    2015-07-01

    This study was conducted with the aim of developing a microbubble agent for near-infrared (NIR) fluorescence and ultrasound dual-modality contrast microbubbles applicable to imaging of sentinel lymph nodes in the VX2 rabbit tumor model. Specific ligands of phosphatidylserine (PS) and Cy7 NIR fluorescent dyes with long emission wavelengths (750-900 nm) were conjugated to the surface of ultrasound contrast microbubbles (MBs), termed Cy7 PS MBs. Ultrasound lymphography and NIR fluorescence imaging were performed using subcutaneous injection of Cy7 PS MBs to visualize the sentinel lymph node. Sentinel lymph node detection rates using the patent blue method, ultrasound lymphography and NIR fluorescence imaging were 95%, 79% and 95%, respectively, and sensitivity was 87%, 74% and 92%, respectively. With 2-D ultrasound, the diagnostic sensitivity for detection of sentinel lymph node metastases was 60% and the specificity was 74%, whereas Cy7 PS MB-enhanced ultrasound had a sensitivity of 80% and a specificity of 87%. The results indicate that dual-modality Cy7 PS MBs combined with ultrasound lymphography and NIR fluorescence may be useful in the detection of normal and metastasized sentinel lymph nodes. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  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. Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors

    PubMed Central

    Huang, Lili; Shen, Ming; Li, Rongxin; Zhang, Xiangyu; Sun, Ying; Gao, Pei; Fu, Hao; Liu, Hongqiang; He, Yang; Du, Yuqing; Cao, Jun; Duan, Yourong

    2016-01-01

    Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy. PMID:27602579

  3. Oral Tumours

    PubMed Central

    Lecavalier, D.R.; Main, J.H.P.

    1988-01-01

    The authors of this article review briefly the anatomy of the oral soft tissues and describe the more common benign and malignant tumours of the mouth, giving emphasis to their clinical features. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8 PMID:21253197

  4. Tumour angiogenesis.

    PubMed Central

    Arnold, F.

    1985-01-01

    Tumours induce the growth of host blood vessels to support their proliferation. This process of angiogenesis is evoked by specific chemical signals. Recognition of these angiogenic factors has led to experimental methods for cancer diagnosis and for inhibiting malignant growth by specifically blocking neovascularisation. The clinical potential of these techniques is discussed. PMID:2413796

  5. "Concomitant immunity" in murine tumours of non-detectable immunogenicity.

    PubMed Central

    Ruggiero, R. A.; Bustuoabad, O. D.; Bonfil, R. D.; Meiss, R. P.; Pasqualini, C. D.

    1985-01-01

    Various immunization assays were used to demonstrate the lack of immunogenicity of three BALB/c tumours of spontaneous origin and of a fourth one resulting from foreign body tumorigenesis. All four tumours inhibited the growth of a second implant of the same tumour into the contralateral flank. In our tumour models "concomitant immunity" (1) was not mediated by macrophage or T-cell dependent immune reactions: both thymectomized BALB/c and nude mice (treated or untreated with silica) gave the same results as intact mice; (2) showed some degree of non-specificity, inhibiting the growth of a different tumour in 3/4 cases; though, the existence of a specific component could not be discarded; (3) was proportional to the volume of the primary tumour at the time of the second challenge; (4) was dependent on actively growing primary tumour, not being obtained with progressively increasing daily inocula of irradiated tumour cells; (5) was detectable in an actively growing secondary tumour; recurrent growth after partial surgical excision was inhibited and (6) involved cytostasis of the secondary tumour: a syngeneic graft of the overlying skin led to tumour growth while histological studies revealed the presence of viable tumour cells. It is postulated that "concomitant immunity" or resistance can be generated without the active participation of the immune system and that tumour-related factors are, in certain cases, responsible for blocking the growth of secondary tumours. Images Figure 5 PMID:2981538

  6. Urogenital tumours in childhood

    PubMed Central

    Swinson, S.

    2011-01-01

    Abstract The commonest urogenital tumours in childhood are Wilms tumour of the kidney and rhabdomyosarcoma in the pelvis. We review these tumours along with other primary renal tumours and less common ovarian and testicular tumours in childhood. Current clinical concepts, relevant staging investigations and imaging features are described. PMID:22187115

  7. 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.

  8. 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

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

    PubMed

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

    2016-01-25

    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.

  10. Phase stability of the nanolaminates V2Ga2C and (Mo1–xVx)2Ga2C from first-principles calculations† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6cp00802j Click here for additional data file. Click here for additional data file.

    PubMed Central

    Dahlqvist, M.; Alling, B.; Rosen, J.

    2016-01-01

    We here use first-principles calculations to investigate the phase stability of the hypothetical laminated material V2Ga2C and the related alloy (Mo1–xVx)2Ga2C, the latter for a potential parent material for synthesis of (Mo1–xVx)2C, a new two-dimensional material in the family of so called MXenes. We predict that V2Ga2C is thermodynamically stable with respect to all identified competing phases in the ternary V–Ga–C phase diagram. We further calculate the stability of ordered and disordered configurations of Mo and V in (Mo1–xVx)2Ga2C and predict that ordered (Mo1–xVx)2Ga2C for x ≤ 0.25 is stable, with an order–disorder transition temperature of ∼1000 K. Furthermore, (Mo1–xVx)2Ga2C for x = 0.5 and x ≥ 0.75 is suggested to be stable, but only for disordered Mo–V configurations, and only at elevated temperatures. We have also investigated the electronic and elastic properties of V2Ga2C; the calculated bulk, shear, and Young's modulus are 141, 94, and 230 GPa, respectively. PMID:27094754

  11. Tumour angiogenesis: the gap between theory and experiments.

    PubMed

    Schofield, J W; Gaffney, E A; Gatenby, R A; Maini, P K

    2011-04-07

    A common experimental technique for viewing in vivo angiogenesis utilises tumours implanted into a test animal cornea. The cornea is avascular but the tumour promotes vascularisation from the limbus and the new blood vessels can be readily observed through the transparent cornea. Many of the early mathematical models for tumour angiogenesis used this scenario as their experimental template and as such assumed that there is a large gap, of the order of 2mm, between the tumour and neighbouring vasculature at the onset of angiogenesis. In this work we consider whether the assumption that there is a significant gap between the tumour and neighbouring vasculature is unique to intra-cornea tumour implants, or whether this characterises avascular tumour growth more generally. To do this we utilise a simple scaling argument, derive a multi-compartment model for tumour growth, and consider in vivo images. This analysis demonstrates that the corneal implant experiments and the corresponding mathematical models cannot generally be applied to a clinical setting. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. The uptake of soluble and nanoparticulate imaging isotope in model liver tumours after intra-venous and intra-arterial administration.

    PubMed

    Stephens, Ross W; Knox, Karen J; Philip, Lee A; Debono, Kelly M; Bell, Jessica L; King, David W; Parish, Christopher R; Senden, Tim J; Tanudji, Marcel R; Winter, Jillean G; Bickley, Stephanie A; Tapner, Michael J; Pang, Jian H; Jones, Stephen K

    2015-01-01

    Delivery of chemotherapeutic drugs to tumours by reformulation as nanoparticles has often been proposed as a means of facilitating increased selective uptake, exploiting the increased permeability of the tumour vasculature. However realisation of this improvement in drug delivery in cancer patients has met with limited success. We have compared tumour uptake of soluble Tc99m-pertechnetate and a colloid of nanoparticles with a Tc99m core, using both intra-venous and intra-arterial routes of administration in a rabbit liver VX2 tumour model. The radiolabelled nanoparticles were tested both in untreated and cationised form. The results from this tumour model in an internal organ show a marked advantage in intra-arterial administration over the intra-venous route, even for the soluble isotope. Tumour accumulation of nanoparticles from arterial administration was augmented by cationisation of the nanoparticle surface with histone proteins, which consistently facilitated selective accumulation within microvessels at the periphery of tumours. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. [Cochlear implant in adults].

    PubMed

    Bouccara, D; Mosnier, I; Bernardeschi, D; Ferrary, E; Sterkers, O

    2012-03-01

    Cochlear implant in adults is a procedure, dedicated to rehabilitate severe to profound hearing loss. Because of technological progresses and their applications for signal strategies, new devices can improve hearing, even in noise conditions. Binaural stimulation, cochlear implant and hearing aid or bilateral cochlear implants are the best opportunities to access to better level of comprehension in all conditions and space localisation. By now minimally invasive surgery is possible to preserve residual hearing and use a double stimulation modality for the same ear: electrical for high frequencies and acoustic for low frequencies. In several conditions, cochlear implant is not possible due to cochlear nerve tumour or major malformations of the inner ear. In these cases, a brainstem implantation can be considered. Clinical data demonstrate that improvement in daily communication, for both cochlear and brainstem implants, is correlated with cerebral activation of auditory cortex.

  14. Extrarenal teratoid Wilms' tumour.

    PubMed

    Chowhan, A K; Reddy, M K; Javvadi, V; Kannan, T

    2011-06-01

    We report an unusual case of extrarenal teratoid Wilms' tumour in a 15-month-old male child. The tumour was retroperitoneal in location and consisted of triphasic Wilms' tumour elements, along with the presence of heterologous components. The heterologous teratoid elements were composed of predominantly glandular epithelium with the presence of focal skeletal muscle, adipose and neuroglial tissues. Although extrarenal Wilms' tumours have been documented in the literature, only a few cases have been noted to date. We present the relevant clinical, radiological, histomorphological, histochemical and immunohistochemical features of this rare tumour, and discuss the various theories of its histogenesis.

  15. Renal angiomyoadenomatous tumour.

    PubMed

    Jayalakshmy, P S; Jose, Merin; Feroze, M; Kumar, Rajesh K

    2017-09-01

    Renal angiomyoadenomatous tumour is a newly described rare neoplasm. This tumour is characterised microscopically by admixture of three components- epithelial cells arranged in tubules and nests, angiomyomatous stroma and capillary sized interconnecting vascular channels in close association with the epithelial cell clusters. Microscopically it has wide range of differential diagnoses which include mixed epithelial and stromal tumour of kidney, angiomyolipoma and clear cell renal cell carcinoma with angiomyolipomatous/angiomyoadenomatous areas. Renal angiomyoadenomatous tumour should be differentiated from these tumours. Till now, only 10 cases have been reported in English medical literature. Here, we are reporting a case of renal angiomyoadenomatous tumour in a 29 year- old female patient who presented with hematuria and low backache and describing its main features so as to differentiate this entity from other renal tumours. To the best of our knowledge, this is the first case to be reported from India.

  16. 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.

  17. Malignant tumours after renal transplantation.

    PubMed

    Fahlenkamp, D; Reinke, P; Kirchner, S; Schnorr, D; Lindeke, A; Loening, S A

    1996-10-01

    In 1243 patients after renal transplantation, 39 malignant tumours were detected in 37 patients. The average latency period between transplantation and tumour disease was 72 months. Tumours included 8 malignant lymphomas, 7 dermatomas and 24 visceral tumours. The patients who developed a tumour had received fewer blood transfusions before transplantation than a tumour-free control group of 60 patients with renal transplants. Rejection crises occurred in a significantly smaller number of tumour patients compared with the control group.

  18. Tumours of the pancreas.

    PubMed

    Kircher, C H; Nielsen, S W

    1976-01-01

    Tumours of the pancreas occur most commonly in dogs and cats and only rarely in other domestic species. The incidence of neoplasms, both exocrine and endocrine, increases with age. Exocrine adenocarcinomas are the most common malignant tumours and have three fairly distinct morphological patterns: small tubular, large tubular, and acinar cell (rare). They readily metastasize, usually before clinical signs are apparent. A "starry sky" pattern with clear histiocytes scattered among tumour cells is a regular feature of poorly differentiated areas of small tubular adenocarcinomas and undifferentiated carcinomas. Islet cell tumours occur in a significant number only in dogs. Metastases are found in about half of the tumours, but malignancy cannot always be predicted by the morphological appearance. Slightly more than half of the islet cell tumours reported in the dog have been associated with clinical signs of hypoglycaemia. Nodular hyperplasia and exocrine adenomas are sometimes difficult to differentiate. Adenomas are considered rare while nodular hyperplasia is common in old animals.

  19. B-1 cells and concomitant immunity in Ehrlich tumour progression.

    PubMed

    Azevedo, M C; Palos, M C; Osugui, L; Laurindo, M F; Masutani, D; Nonogaki, S; Bachi, A L L; Melo, F H M; Mariano, M

    2014-05-01

    Concomitant immunity is a phenomenon in which a tumour-bearing host is resistant to the growth of an implanted secondary tumour. Metastases are considered to be secondary tumours that develop spontaneously during primary tumour growth, suggesting the involvement of concomitant immunity in controlling the rise of metastases. It has been demonstrated that B-1 cells, a subset of B-lymphocytes found predominantly in pleural and peritoneal cavities, not only increase the metastatic development of murine melanoma B16F10, but also are capable of differentiating into mononuclear phagocytes, modulating inflammatory responses in wound healing, in oral tolerance and in Paracoccidiose brasiliensis infections. Here, we studied B-1 cells' participation in concomitant immunity during Ehrlich tumour progression. Our results show that B-1 cells obtained from BALB/c mice previously injected with Ehrlich tumour in the footpad were able to protect BALB/c and BALB/Xid mice against Ehrlich tumour challenge. In addition, it was demonstrated that BALB/Xid show faster tumour growth and have lost concomitant immunity, and that this state can be partially restored by reconstituting these animals with B-1 cells. However, further researches are required to establish the mechanism involving B-1 cells in Ehrlich tumour growth. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. Endolymphatic sac tumour.

    PubMed

    Zulkarnaen, Mohammad; Tang, Ing Ping; Wong, Siong Lung

    2012-06-01

    We present a case of a papillary tumour at the cerebellopontine angle in a 41-year-old man. He presented with left-sided facial and ear pain associated with dizziness, nystagmus and hearing loss. CT scan of the temporal bone showed a destructive tumour at the left cerebellopontine angle. Surgical excision was performed and the diagnosis of the endolymphatic sac tumour was made. Endolymphatic tumour is a low grade adenocarcinoma that originates from the endolymphatic sac. The definitive diagnosis requires a combination of clinical features, radiological finding and pathological correlation.

  1. 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

  2. Parapharyngeal space primary tumours.

    PubMed

    Grilli, Gianluigi; Suarez, Vanessa; Muñoz, María Gabriela; Costales, María; Llorente, José Luis

    The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  3. Tumours and tumour mimics in the olecranon.

    PubMed

    Kularatne, U; James, S L J; Evans, N; Tyrrell, P N M; Singh, J

    2015-07-01

    Lesions in the olecranon are rare and may be identified during the investigation of a clinically suspected abnormality or as an incidental finding. This review describes the spectrum of tumours and tumour-like lesions that can involve the olecranon and illustrates the radiographic, CT, and MRI appearances that may facilitate diagnosis. A variety of pathological processes affecting the olecranon are presented and discussed including the epidemiology and imaging features. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  4. Progressive dysembryoplastic neuroepithelial tumour.

    PubMed

    Alexander, Hamish; Tannenburg, Anthony; Walker, David G; Coyne, Terry

    2015-01-01

    Dysembryoplastic neuroepithelial tumour (DNET) is a benign tumour characterised by cortical location and presentation with drug resistant partial seizures in children. Recently the potential for malignant transformation has been reported, however progression without malignant transformation remains rare. We report a case of clinical and radiologic progression of a DNET in a girl 10 years after initial biopsy.

  5. 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

  6. Model simulation and experimental validation of intratumoral chemotherapy using multiple polymer implants.

    PubMed

    Weinberg, Brent D; Patel, Ravi B; Wu, Hanping; Blanco, Elvin; Barnett, Carlton C; Exner, Agata A; Saidel, Gerald M; Gao, Jinming

    2008-10-01

    Radiofrequency ablation has emerged as a minimally invasive option for liver cancer treatment, but local tumor recurrence is common. To eliminate residual tumor cells in the ablated tumor, biodegradable polymer millirods have been designed for local drug (e.g., doxorubicin) delivery. A limitation of this method has been the extent of drug penetration into the tumor (<5 mm), especially in the peripheral tumor rim where thermal ablation is less effective. To provide drug concentration above the therapeutic level as needed throughout a large tumor, implant strategies with multiple millirods were devised using a computational model. This dynamic, 3-D mass balance model of drug distribution in tissue was used to simulate the consequences of various numbers of implants in different locations. Experimental testing of model predictions was performed in a rabbit VX2 carcinoma model. This study demonstrates the value of multiple implants to provide therapeutic drug levels in large ablated tumors.

  7. Model Simulation and Experimental Validation of Intratumoral Chemotherapy Using Multiple Polymer Implants

    PubMed Central

    Weinberg, Brent D.; Patel, Ravi B.; Wu, Hanping; Blanco, Elvin; Barnett, Carlton C.; Exner, Agata A.; Saidel, Gerald M.; Gao, Jinming

    2017-01-01

    Radiofrequency ablation has emerged as a minimally invasive option for liver cancer treatment, but local tumor recurrence is common. To eliminate residual tumor cells in the ablated tumor, biodegradable polymer millirods have been designed for local drug (e.g., doxorubicin) delivery. A limitation of this method has been the extent of drug penetration into the tumor (< 5 mm), especially in the peripheral tumor rim where thermal ablation is less effective. To provide drug concentration above the therapeutic level as needed throughout a large tumor, implant strategies with multiple millirods were devised using a computational model. This dynamic, 3-D mass balance model of drug distribution in tissue was used to simulate the consequences of various numbers of implants in different locations. Experimental testing of model predictions was performed in a rabbit VX2 carcinoma model. This study demonstrates the value of multiple implants to provide therapeutic drug levels in large ablated tumors. PMID:18523817

  8. Tumour ablation: technical aspects.

    PubMed

    Widmann, Gerlig; Bodner, Gerd; Bale, Reto

    2009-10-02

    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.

  9. 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.

  10. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion.

    PubMed

    Yanagie, Hironobu; Kumada, Hiroaki; Nakamura, Takemi; Higashi, Syushi; Ikushima, Ichiro; Morishita, Yasuyuki; Shinohara, Atsuko; Fijihara, Mitsuteru; Suzuki, Minoru; Sakurai, Yoshinori; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Nishimura, Ryohei; Ono, Koji; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Takahashi, Hiroyuki

    2011-12-01

    Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of (10)B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared (10)BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), (10)BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. The (10)B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that (10)B entrapped WOW emulsion could be applied to novel intra-arterial boron delivery carrier

  11. 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.

  12. The profile of melatonin production in tumour-bearing rats.

    PubMed

    Ferreira, Ana Carolina Franco; Martins, Eivor; Afeche, Solange Castro; Cipolla-Neto, José; Costa Rosa, Luís Fernando Bicudo Pereira

    2004-09-24

    The pineal gland is involved in the regulation of tumour growth through the anticancer activity of melatonin, which presents immunomodulatory, anti-proliferative and anti-oxidant effects. In this study we measured melatonin content directly in the pineal gland, in an attempt to clarify the modulation of pineal melatonin secretory activity during tumour growth. Different groups of Walker 256 carcinosarcoma bearing rats were sacrificed at 12 different time points during 24h (12h:12h light/dark cycle) on different days during the tumour development (on the first, seventh and fourteenth day after tumour inoculation). Melatonin content in the pineal gland was determined by high-performance liquid chromatography with electrochemical detection. During tumour development the amount of melatonin secreted increased from 310.9 ng/mg of protein per day from control animals, to 918.1 ng/mg of protein per day 14 days after tumour implantation, and there were changes in the pineal production profile of melatonin. Cultured pineal glands obtained from tumour-bearing rats turned out to be less responsive to noradrenaline, suggesting the existence, in vivo, of putative factor(s) modulating pineal melatonin production. The results demonstrated that during tumour development there is a modification of pineal melatonin production daily profile, possibly contributing to cachexia, associated to changes in pineal gland response to noradrenaline stimulation.

  13. Tumour-induced osteomalacia.

    PubMed

    Minisola, Salvatore; Peacock, Munro; Fukumoto, Seijii; Cipriani, Cristiana; Pepe, Jessica; Tella, Sri Harsha; Collins, Michael T

    2017-07-13

    Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 (FGF23). Owing to the role of FGF23 in renal phosphate handling and vitamin D synthesis, TIO is characterized by decreased renal tubular reabsorption of phosphate, by hypophosphataemia and by low levels of active vitamin D. Chronic hypophosphataemia ultimately results in osteomalacia (that is, inadequate bone mineralization). The diagnosis of TIO is usually suspected when serum phosphate levels are chronically low in the setting of bone pain, fragility fractures and muscle weakness. Locating the offending tumour can be very difficult, as the tumour is often very small and can be anywhere in the body. Surgical removal of the tumour is the only definitive treatment. When the tumour cannot be located or when complete resection is not possible, medical treatment with phosphate salts or active vitamin D is necessary. One of the most promising emerging treatments for unresectable tumours that cause TIO is the anti-FGF23 monoclonal antibody KRN23. The recent identification of a fusion of fibronectin and fibroblast growth factor receptor 1 (FGFR1) as a molecular driver in some tumours not only sheds light on the pathophysiology of TIO but also opens the door to a better understanding of the transcription, translocation, post-translational modification and secretion of FGF23, as well as suggesting approaches to targeted therapy. Further study will reveal if the FGFR1 pathway is also involved in tumours that do not harbour the translocation.

  14. [Gastric mesenchymal tumours (GIST)].

    PubMed

    Spivach, Arrigo; Fezzi, Margherita; Sartori, Alberto; Belgrano, Manuel; Rimondini, Alessandra; Cuttin-Zernich, Roberto; Covab, Maria Assunta; Bonifacio, Daniela; Buri, Luigi; Pagani, Carlo; Zanconati, Fabrizio

    2008-01-01

    The incidence of gastrointestinal stromal tumours (GIST) has increased in recent years. A number of authors have attempted to define the actual nature of these tumours. Immunohistochemistry highlighting the positivity of tyrosine-kinase (CD117/c-Kit) has revealed the difference between gastrointestinal stromal tumours and other mesenchymal tumours and, therefore, the possibility of medical rather than surgical therapy. We retrospectively reviewed 19 patients affected by primary gastric GIST, who underwent surgery in recent years with subsequent follow-up. Gastroscopy and gastrointestinal tract radiography were used not only to obtain the diagnosis but also to establish the size, density, contours, ulceration, regional lymphadenopathy, mesenteric infiltration and the presence of metastases. The aim of this study was to evaluate the roles of endoscopy and radiology in this pathology and the advantages and limitations of each individual technique.

  15. 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

  16. Modular endoprosthetic replacement for metastatic tumours of the proximal femur

    PubMed Central

    Chandrasekar, Coonoor R; Grimer, Robert J; Carter, Simon R; Tillman, Roger M; Abudu, Adesegun T

    2008-01-01

    Background and aims Endoprosthetic replacements of the proximal femur are commonly required to treat destructive metastases with either impending or actual pathological fractures at this site. Modular prostheses provide an off the shelf availability and can be adapted to most reconstructive situations for proximal femoral replacements. The aim of this study was to assess the clinical and functional outcomes following modular tumour prosthesis reconstruction of the proximal femur in 100 consecutive patients with metastatic tumours and to compare them with the published results of patients with modular and custom made endoprosthetic replacements. Methods 100 consecutive patients who underwent modular tumour prosthetic reconstruction of the proximal femur for metastases using the METS system from 2001 to 2007 were studied. The patient, tumour and treatment factors in relation to overall survival, local control, implant survival and complications were analysed. Functional scores were obtained from surviving patients. Results and conclusion There were 45 male and 55 female patients. The mean age was 60.2 years. The indications were metastases. Seventy five patients presented with pathological fracture or with failed fixation and 25 patients were at a high risk of developing a fracture. The mean follow up was 15.9 months [range 0–77]. Three patients died within 2 weeks following surgery. 69 patients have died and 31 are alive. Of the 69 patients who were dead 68 did not need revision surgery indicating that the implant provided single definitive treatment which outlived the patient. There were three dislocations (2/5 with THR and 1/95 with unipolar femoral heads). 6 patients had deep infections. The estimated five year implant survival (Kaplan-Meier analysis) was 83.1% with revision as end point. The mean TESS score was 64% (54%–82%). We conclude that METS modular tumour prosthesis for proximal femur provides versatility; low implant related complications and

  17. Cochlear Implants

    MedlinePlus

    ... Medical Procedures Implants and Prosthetics Cochlear Implants Cochlear Implants Share Tweet Linkedin Pin it More sharing options ... normal ear, ear with hearing loss, and cochlear implant procedure Welcome to the Food and Drug Administration ( ...

  18. Predicting tumour response

    PubMed Central

    Law, W. Phillip; Miles, Kenneth A.

    2013-01-01

    Abstract Response prediction is an important emerging concept in oncologic imaging, with tailored, individualized treatment regimens increasingly becoming the standard of care. This review aims to define tumour response and illustrate the ways in which imaging techniques can demonstrate tumour biological characteristics that provide information on the likely benefit to be received by treatment. Two imaging approaches are described: identification of therapeutic targets and depiction of the treatment-resistant phenotype. The former approach is exemplified by the use of radionuclide imaging to confirm target expression before radionuclide therapy but with angiogenesis imaging and imaging correlates for genetic response predictors also demonstrating potential utility. Techniques to assess the treatment-resistant phenotype include demonstration of hypoperfusion with dynamic contrast-enhanced computed tomography and magnetic resonance imaging (MRI), depiction of necrosis with diffusion-weighted MRI, imaging of hypoxia and tumour adaption to hypoxia, and 99mTc-MIBI imaging of P-glycoprotein mediated drug resistance. To date, introduction of these techniques into clinical practice has often been constrained by inadequate cross-validation of predictive criteria and lack of verification against appropriate response end points such as survival. With further refinement, imaging predictors of response could play an important role in oncology, contributing to individualization of therapy based on the specific tumour phenotype. This ability to predict tumour response will have implications for improving efficacy of treatment, cost-effectiveness and omission of futile therapy. PMID:24061161

  19. 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.

  20. The determinants of tumour immunogenicity

    PubMed Central

    Blankenstein, Thomas; Coulie, Pierre G.; Gilboa, Eli; Jaffee, Elizabeth M.

    2013-01-01

    Many standard and targeted therapies, as well as radiotherapy, have been shown to induce an anti-tumour immune response, and immunotherapies rely on modulating the host immune system to induce an anti-tumour immune response. However, the immune response to such therapies is often reliant on the immunogenicity of a tumour. Tumour immunogenicity varies greatly between cancers of the same type in different individuals and between different types of cancer. So, what do we know about tumour immunogenicity and how might we therapeutically improve tumour immunogenicity? We asked four leading cancer immunologists around the world for their opinions on this important issue. PMID:22378190

  1. Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma

    PubMed Central

    Johansson, M; Henriksson, R; Bergenheim, A T; Koskinen, L-O D

    2000-01-01

    Biotherapy including interleukin-2 (IL-2) treatment seems to be more effective outside the central nervous system when compared to the effects obtained when the same tumour is located intracerebrally. Recently published studies suggest that reduced activity of NK cells in tumour tissue can be increased by histamine. The present study was designed to determine whether IL-2 and histamine, alone or in combination, can induce anti-tumour effects in an orthotopic rat glioma model. One group of rats was treated with histamine alone (4 mg kg–1s.c. as daily injections from day 6 after intracranial tumour implantation), another group with IL-2 alone as a continuous subcutaneous infusion and a third group with both histamine and IL-2. The animals were sacrificed at day 24 after tumour implantation. IL-2 and histamine in combination significantly reduced tumour growth. The microvessel density was significantly reduced, an effect mainly affecting the small vessels. No obvious alteration in the pattern of VEGF mRNA expression was evident and no significant changes in apoptosis were observed. Neither IL-2 nor histamine alone caused any detectable effects on tumour growth. Histamine caused an early and pronounced decline in tumour blood flow compared to normal brain. The results indicate that the novel combination of IL-2 and histamine can be of value in reducing intracerebral tumour growth and, thus, it might be of interest to re-evaluate the therapeutic potential of biotherapy in malignant glioma. © 2000 Cancer Research Campaign PMID:10952789

  2. Microenvironmental autophagy promotes tumour growth.

    PubMed

    Katheder, Nadja S; Khezri, Rojyar; O'Farrell, Fergal; Schultz, Sebastian W; Jain, Ashish; Rahman, Mohammed M; Schink, Kay O; Theodossiou, Theodossis A; Johansen, Terje; Juhász, Gábor; Bilder, David; Brech, Andreas; Stenmark, Harald; Rusten, Tor Erik

    2017-01-19

    As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment. Induction of autophagy is mediated by Drosophila tumour necrosis factor and interleukin-6-like signalling from metabolically stressed tumour cells, whereas tumour growth depends on active amino acid transport. We show that dormant growth-impaired tumours from autophagy-deficient animals reactivate tumorous growth when transplanted into autophagy-proficient hosts. We conclude that transformed cells engage surrounding normal cells as active and essential microenvironmental contributors to early tumour growth through nutrient-generating autophagy.

  3. Vasculogenesis: a crucial player in the resistance of solid tumours to radiotherapy

    PubMed Central

    2014-01-01

    Tumours have two main ways to develop a vasculature: by angiogenesis, the sprouting of endothelial cells from nearby blood vessels, and vasculogenesis, the formation of blood vessels from circulating cells. Because tumour irradiation abrogates local angiogenesis, the tumour must rely on the vasculogenesis pathway for regrowth after irradiation. Tumour irradiation produces a marked influx of CD11b+ myeloid cells (macrophages) into the tumours, and these are crucial to the formation of blood vessels in the tumours after irradiation and for the recurrence of the tumours. This process is driven by increased tumour hypoxia, which increases levels of HIF-1 (hypoxia-inducible factor 1), which in turn upregulates SDF-1 (stromal cell-derived factor 1 or CXCL12), the main driver of the vasculogenesis pathway. Inhibition of HIF-1 or of its downstream target SDF-1 prevents the radiation-induced influx of the CD11b+ myeloid cells and delays or prevents the tumours from recurring following irradiation. Others and we have shown that with a variety of tumours in both mice and rats, the inhibition of the SDF-1/CXCR4 pathway delays or prevents the recurrence of implanted or autochthonous tumours following irradiation or following treatment with vascular disrupting agents or some chemotherapeutic drugs such as paclitaxel. In addition to the recruited macrophages, endothelial progenitor cells (EPCs) are also recruited to the irradiated tumours, a process also driven by SDF-1. Together, the recruited proangiogenic macrophages and the EPCs reform the tumour vasculature and allow the tumour to regrow following irradiation. This is a new paradigm with major implications for the treatment of solid tumours by radiotherapy. PMID:24338942

  4. Macrophage migration inhibitory factor produced by the tumour stroma but not by tumour cells regulates angiogenesis in the B16-F10 melanoma model

    PubMed Central

    Girard, E; Strathdee, C; Trueblood, E; Quéva, C

    2012-01-01

    Background: Macrophage migration inhibitory factor (MIF) has been proposed as a link between inflammation and tumorigenesis. Despite its potentially broad influence in tumour biology and prevalent expression, the value of MIF as a therapeutic target in cancer remains unclear. We sought to validate MIF in tumour models by achieving a complete inhibition of its expression in tumour cells and in the tumour stroma. Methods: We used MIF shRNA-transduced B16-F10 melanoma cells implanted in wild-type and MIF−/− C57Bl6 mice to investigate the effect of loss of MIF on tumour growth. Cytokine detection and immunohistochemistry (IHC) were used to evaluate tumours ex vivo. Results: Macrophage migration inhibitory factor shRNA inhibited expression of MIF protein by B16-F10 melanoma cells in vitro and in vivo. In vitro, the loss of MIF in this cell line resulted in a decreased response to hypoxia as indicated by reduced expression of VEGF. In vivo the growth of B16-F10 tumours was inhibited by an average of 47% in the MIF−/− mice compared with wild-type but was unaffected by loss of MIF expression by the tumour cells. Immunohistochemistry analysis revealed that microvessel density was decreased in tumours implanted in the MIF−/− mice. Profiling of serum cytokines showed a decrease in pro-angiogenic cytokines in MIF−/− mice. Conclusion: We report that the absence of MIF in the host resulted in slower tumour growth, which was associated with reduced vascularity. While the major contribution of MIF appeared to be in the regulation of angiogenesis, tumour cell-derived MIF played a negligible role in this process. PMID:22955855

  5. Percutaneous renal tumour biopsy.

    PubMed

    Delahunt, Brett; Samaratunga, Hemamali; Martignoni, Guido; Srigley, John R; Evans, Andrew J; Brunelli, Matteo

    2014-09-01

    The use of percutaneous renal tumour biopsy (RTB) as a diagnostic tool for the histological characterization of renal masses has increased dramatically within the last 30 years. This increased utilization has paralleled advances in imaging techniques and an evolving knowledge of the clinical value of nephron sparing surgery. Improved biopsy techniques using image guidance, coupled with the use of smaller gauge needles has led to a decrease in complication rates. Reports from series containing a large number of cases have shown the non-diagnostic rate of RTB to range from 4% to 21%. Re-biopsy has been shown to reduce this rate, while the use of molecular markers further improves diagnostic sensitivity. In parallel with refinements of the biopsy procedure, there has been a rapid expansion in our understanding of the complexity of renal cell neoplasia. The 2013 Vancouver Classification is the current classification for renal tumours, and contains five additional entities recognized as novel forms of renal malignancy. The diagnosis of tumour morphotype on RTB is usually achievable on routine histology; however, immunohistochemical studies may be of assistance in difficult cases. The morphology of the main tumour subtypes, based upon the Vancouver Classification, is described and differentiating features are discussed. © 2014 John Wiley & Sons Ltd.

  6. 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

  7. Why measure tumours?

    PubMed

    Olsen, Øystein E

    2015-01-01

    This article questions the scientific justification of ingrained radiologic practices exemplified by size measurements of childhood solid tumours. This is approached by a critical review of staging systems from a selection of paediatric oncological treatment protocols. Local staging remains size-dependent for some tumour types. The consequent stage assignment can significantly influence treatment intensity. Still, the protocols tend not to give precise guidance on how to perform scans and standardise measurements. Also, they do not estimate or account for the inevitable variability in measurements. Counts and measurements of lung nodules are, within some tumour groups, used for diagnosis of metastatic disease. There is, however, no evidence that nodule size is a useful discriminator of benign and malignant lung nodules. The efficacy of imaging depends chiefly on observations being precise, accurate and valid for the desired diagnostic purpose. Because measurements without estimates of their errors are meaningless, studies of variability dependent on tumour shape and location, imaging device and observer need to be encouraged. Reproducible observations make good candidates for staging parameters if they have prognostic validity and at the same time show little covariation with (thereby adding new information to) the existing staging system. The lack of scientific rigour has made the validity of size measurement very difficult to assess. Action is needed, the most important being radiologists' active contribution in development of oncological staging systems, attention to standardisation, knowledge about errors in measurement and protection against undue influence of such errors in the staging of the individual child.

  8. Metastasising pilar tumour of scalp.

    PubMed Central

    Batman, P A; Evans, H J

    1986-01-01

    A case of pilar tumour of the scalp, treated by local excision and radiotherapy, later metastasised to the neck. The variable histological growth patterns of the primary tumour and its metastases are described. It is concluded that the pilar tumour is a genuine neoplasm of the hair follicle that is occasionally capable of malignant behaviour. Images PMID:3734112

  9. 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…

  10. 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…

  11. Gastrointestinal stromal tumour and second tumours: A literature review.

    PubMed

    Núñez-Martín, Rafael; Cubedo Cervera, Ricardo; Provencio Pulla, Mariano

    2017-07-20

    There are several tumours associated with gastrointestinal stromal tumour (GIST), most of them without an apparent family relationship; only 5% of them occur within the context of a family syndrome. In this article the corresponding literature about the former has been reviewed. A search in Pubmed was carried out, the methodology of which is described in detail in the body of the article. A total of 88 articles have been chosen for the review, next to the application of limits as well as a manual review. GIST patients have a twofold risk of developing a second tumour than the general population (4-33% of them develop a second neoplasm, either synchronic or metachronic). Most incident tumours associated with GIST are gastrointestinal and genitourinary tumours. In addition, patients with second tumours have a worse survival rate than those without second tumours. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  12. Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity

    PubMed Central

    Gigi, V; Stein, J; Askenasy, N; Yaniv, I; Ash, S

    2013-01-01

    Background: Perspectives of immunotherapy to cancer mediated by bone marrow transplantation (BMT) in conjunction with dendritic cell (DC)-mediated immune sensitisation have yielded modest success so far. In this study, we assessed the impact of DC on graft vs tumour (GvT) reactions triggered by allogeneic BMT. Methods: H2Ka mice implanted with congenic subcutaneous Neuro-2a neuroblastoma (NB, H2Ka) tumours were irradiated and grafted with allogeneic H2Kb bone marrow cells (BMC) followed by immunisation with tumour-inexperienced or tumour-pulsed DC. Results: Immunisation with tumour-pulsed donor DC after allogeneic BMT suppressed tumour growth through induction of T cell-mediated NB cell lysis. Early post-transplant administration of DC was more effective than delayed immunisation, with similar efficacy of DC inoculated into the tumour and intravenously. In addition, tumour inexperienced DC were equally effective as tumour-pulsed DC in suppression of tumour growth. Immunisation of DC did not impact quantitative immune reconstitution, however, it enhanced T-cell maturation as evident from interferon-γ (IFN-γ) secretion, proliferation in response to mitogenic stimulation and tumour cell lysis in vitro. Dendritic cells potentiate GvT reactivity both through activation of T cells and specific sensitisation against tumour antigens. We found that during pulsing with tumour lysate DC also elaborate a factor that selectively inhibits lymphocyte proliferation, which is however abolished by humoral and DC-mediated lymphocyte activation. Conclusion: These data reveal complex involvement of antigen-presenting cells in GvT reactions, suggesting that the limited success in clinical application is not a result of limited efficacy but suboptimal implementation. Although DC can amplify soluble signals from NB lysates that inhibit lymphocyte proliferation, early administration of DC is a dominant factor in suppression of tumour growth. PMID:23511628

  13. Trafficking of activated lymphocytes into the RENCA tumour microcirculation in vivo in mice.

    PubMed Central

    Brown, N. J.; Ali, S.; Reed, M. W.; Wiltrout, R.; Rees, R. C.

    1997-01-01

    The aim of the study was to establish a model of tumour microcirculation in vivo using the murine renal cell carcinoma cell line (RENCA) implanted into the mouse cremaster muscle, and subsequently to investigate the trafficking of syngeneic lymphocyte subpopulations into both the RENCA tumour and the surrounding normal cremaster muscle microcirculation. We have demonstrated that RENCA tumour cells, at a dose of 1.5 x 10(5) per 30 microl injected into the cremaster muscle, reproducibly produced a vascularized tumour suitable for in vivo microscopy at 10-14 days. Injection of fluorescently labelled effector cells (1 x 10(6)) including naive splenocytes, T-cell enriched populations and ex vivo interleukin 2 (IL-2)-activated splenocytes all migrated to and flowed through both the tumour and the normal microcirculation, with negligible adhesion. However, we observed the selective recruitment, localization and arrest of IL-2-activated splenocytes (P < 0.05) into the tumour microcirculation, and the subsequent extravasation of cells into the tumour intestitium in some instances. This did not occur with the other effector cells. We also observed the absence of leucocyte rolling in the tumour microcirculation, suggesting an impairment in adhesion molecule expression on the tumour endothelium. We have therefore established the potential of this model for defining further effector cell-tumour-endothelium interactions. PMID:9413944

  14. Warfarin inhibits metastasis of Mtln3 rat mammary carcinoma without affecting primary tumour growth.

    PubMed Central

    McCulloch, P.; George, W. D.

    1989-01-01

    Coumarin anticoagulants inhibit metastasis in several animal models, but the mechanism of this effect is uncertain. In order to determine the role of cytotoxic and/or cytostatic actions of coumarins on the tumour cells, we have studied the effects of warfarin on tumour cell growth in a model in which tumour metastasis is inhibited by this drug. Clonogenic assay, growth curve analysis and thymidine labelling index revealed that warfarin had no effects on Mtln3 mammary carcinoma cell growth in vitro at concentrations below 1 mM. The growth rate of subcutaneously implanted Mtln3 tumour deposits in female F344 rats, assessed by weight and by stathmokinetic analysis of the tumour tissue, was identical in warfarin-treated and control animals. Spontaneous metastasis from such tumours to the lungs was, however, significantly reduced in warfarin-treated animals (median 0 pulmonary tumours per animal in warfarin treated, eight tumours per animal in control animals; P less than 0.05, Mann-Whitney). The mean plasma warfarin concentration in warfarin treated rats was 1.63 microM. These results suggest that warfarin treatment of the host animal can inhibit tumour metastasis without having any direct or indirect effect on the growth rate of the tumour cells. PMID:2930682

  15. Telomerase activity (TMA) in tumour and peritumoural tissues in a rat liver cancer model.

    PubMed

    Zhang, Huo-Jun; Yang, Ji-Jin; Tian, Jian-Ming; Wang, Pei-Jun; Shao, Cheng-Wei; Zuo, Chang-Jing; Zhang, Shun-Min; Gupta, Sanjay

    2009-02-01

    To study the levels of telomerase activity (TMA) in tumour and peritumoural tissues in a liver cancer model in rats, and to study the change in TMA expression over time. Using the telomeric repeated amplification protocol (TRAP), TMA was measured in tumour tissue, peritumoural tissue and normal liver tissue of Walker-256 tumour-bearing rats at 4, 6 and 8 days after tumour implantation. TMA at day 4, 6 and 8 was 0.767+/-0.117, 0.768+/-0.118 and 0.774+/-0.111 in tumour tissue, 0.389+/-0.263, 0.492+/-0.253 and 0.584+/-0.239 in peritumoural tissue, and 0.231+/-0.022, 0.229+/-0.022 and 0.233+/-0.021 in normal liver tissue, respectively. TMA in tumour tissue was higher than that in peri-tumour and normal liver tissues at all time points of measurement (P < 0.05). The TMA levels in tumour tissue and normal liver tissue did not show any change over time. TMA level in the peritumoural tissue increased with time; TMA level in animals sacrificed at day 8 was higher than that seen in animals sacrificed at day 4 (P < 0.05). TMA in walker-256 tumour-bearing rats was higher than that in normal and peritumoural tissues. TMA level in the peritumoural tissue increased with time suggesting that TMA activation in peritumoural tissue may be an important factor promoting tumour growth.

  16. Radiotherapy in Phyllodes Tumour

    PubMed Central

    Sasidharan, Balukrishna; Manipadam, Marie Therese; Paul, M J; Backianathan, Selvamani

    2017-01-01

    Introduction Phyllodes Tumour (PT) of the breast is a relatively rare breast neoplasm (<1%) with diverse range of pathology and biological behaviour. Aim To describe the clinical course of PT and to define the role of Radiotherapy (RT) in PT of the breast. Materials and Methods Retrospective analysis of hospital data of patients with PT presented from 2005 to 2014 was done. Descriptive statistics was used to analyze the results. Simple description of data was done in this study. Age and duration of symptoms were expressed in median and range. Percentages, tables and general discussions were used to understand the meaning of the data analyzed. Results Out of the 98 patients, 92 were eligible for analysis. The median age of presentation was 43 years. A total of 64/92 patients were premenopausal. There was no side predilection for this tumour but 57/92 patients presented as an upper outer quadrant lump. Fifty percent of the patients presented as giant (10 cm) PT. The median duration of symptoms was 12 months (range: 1-168 months). A 60% of patients had Benign (B), 23% had Borderline (BL) and 17% had malignant (M) tumours. The surgical treatment for benign histology included Lumpectomy (L) for 15%, Wide Local Excision (WLE) for 48%, and Simple Mastectomy (SM) for 37%. All BL and M tumours were treated with WLE or SM. There was no recurrence in B and BL group when the margin was ≥1 cm. All non-metastatic M tumours received adjuvant RT irrespective of their margin status. Total 3/16 patients with M developed local recurrence. Total 6/16 M patients had distant metastases (lung or bone). Our median duration of follow up was 20 months (range: 1-120 months). Conclusion Surgical resection with adequate margins (>1 cm) gave excellent local control in B and BL tumours. For patients with BL PT, local radiotherapy is useful, if margins are close or positive even after the best surgical resection. There is a trend towards improved local control with adjuvant radiotherapy for

  17. Penile Implants

    MedlinePlus

    Penile Implants Overview By Mayo Clinic Staff Penile implants are devices placed inside the penis to allow men with erectile dysfunction (ED) to get an erection. Penile implants are typically recommended after other treatments for ED ...

  18. Dental Implants.

    PubMed

    Griggs, Jason A

    2017-10-01

    Systematic reviews of literature over the period between 2008 and 2017 are discussed regarding clinical evidence for the factors affecting survival and failure of dental implants. The factors addressed include publication bias, tooth location, insertion torque, collar design, implant-abutment connection design, implant length, implant width, bone augmentation, platform switching, surface roughness, implant coatings, and the use of ceramic materials in the implant body and abutment. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. Diagnosing Musculoskeletal Tumours

    PubMed Central

    Carter, Simon R.; Spooner, David; Sneath, Rodney S.

    2001-01-01

    In 1993 we became aware of a worrying increase in apparent errors in the histopathological diagnosis of musculoskeletal tumours in our Unit. As a result all cases seen over the past 8 years were reviewed by an independent panel. Of the 1996 cases reviewed there was an error in 87. In 54 cases (2.7%) this had led to some significant change in the active management of the patient. The main areas where errors arose were in those very cases where clinical and radiological features were not helpful in confirming or refuting the diagnosis. The incidence of errors rose with the passage of time, possibly related to a deterioration in the pathologist’s health. The error rate in diagnosing bone tumours in previously published series ranges from 9 to 40%. To ensure as accurate a rate of diagnosis as possible multidisciplinary working and regular audit are essential. PMID:18521309

  1. 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

  2. [Adrenal tumours in childhood].

    PubMed

    Martos-Moreno, G A; Pozo-Román, J; Argente, J

    2013-09-01

    This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy.

  3. [Phyllodes tumour: a rare, rapidly growing breast tumour].

    PubMed

    den Exter, Paul L; Hornstra, Bonne J; Vree, Robbert

    2009-01-01

    A 40-year-old woman presented at the breast outpatient clinic with a giant tumour of her left breast. The size, rapid growth and radiological characteristics of the lesion led us to suspect a phyllodes tumour. A histological examination of a needle biopsy confirmed this diagnosis. An additional CT scan revealed no signs of metastases. We performed a mastectomy during which a tumour measuring 48 x 33 x 25 cm was resected. Histological examination revealed a borderline phyllodes tumour. Phyllodes tumours are rare fibroepithelial neoplasms of the breast and pre-operatively these are often difficult to differentiate from fibroadenomas. Phyllodes tumours have a variable clinical course with the ability to metastasize and a propensity to recur locally. Complete excision with wide margins is essential to prevent local recurrence. In our case, the surgical margins were limited and our patient was therefore treated with postoperative radiation therapy.

  4. 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

  5. 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. © 2014 The Authors. Immunology published by John Wiley & Sons Ltd.

  6. Metabolic scaling in solid tumours

    PubMed Central

    Milotti, E.; Vyshemirsky, V.; Sega, M.; Stella, S.; Chignola, R.

    2013-01-01

    Tumour metabolism is an outstanding topic of cancer research, as it determines the growth rate and the global activity of tumours. Recently, by combining the diffusion of oxygen, nutrients, and metabolites in the extracellular environment, and the internal motions that mix live and dead cells, we derived a growth law of solid tumours which is linked to parameters at the cellular level1. Here we use this growth law to obtain a metabolic scaling law for solid tumours, which is obeyed by tumours of different histotypes both in vitro and in vivo, and we display its relation with the fractal dimension of the distribution of live cells in the tumour mass. The scaling behaviour is related to measurable parameters, with potential applications in the clinical practice. PMID:23727729

  7. Metabolic scaling in solid tumours

    NASA Astrophysics Data System (ADS)

    Milotti, E.; Vyshemirsky, V.; Sega, M.; Stella, S.; Chignola, R.

    2013-06-01

    Tumour metabolism is an outstanding topic of cancer research, as it determines the growth rate and the global activity of tumours. Recently, by combining the diffusion of oxygen, nutrients, and metabolites in the extracellular environment, and the internal motions that mix live and dead cells, we derived a growth law of solid tumours which is linked to parameters at the cellular level. Here we use this growth law to obtain a metabolic scaling law for solid tumours, which is obeyed by tumours of different histotypes both in vitro and in vivo, and we display its relation with the fractal dimension of the distribution of live cells in the tumour mass. The scaling behaviour is related to measurable parameters, with potential applications in the clinical practice.

  8. VEGF targets the tumour cell

    PubMed Central

    Goel, Hira Lal; Mercurio, Arthur M.

    2014-01-01

    The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches. PMID:24263190

  9. VEGF targets the tumour cell.

    PubMed

    Goel, Hira Lal; Mercurio, Arthur M

    2013-12-01

    The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches.

  10. Imaging biomarkers of brain tumour margin and tumour invasion.

    PubMed

    Price, S J; Gillard, J H

    2011-12-01

    Invasion of tumour cells into the normal brain is one of the major reasons of treatment failure for gliomas. Although there is a good understanding of the molecular and cellular processes that occur during this invasion, it is not possible to detect the extent of the tumour with conventional imaging. However, there is an understanding that the degree of invasion differs with individual tumours, and yet they are all treated the same. Newer imaging techniques that probe the pathological changes within tumours may be suitable biomarkers for invasion. Imaging methods are now available that can detect subtle changes in white matter organisation (diffusion tensor imaging), tumour metabolism and cellular proliferation (using MR spectroscopy and positron emission tomography) occurring in regions of tumour that cannot be detected by conventional imaging. The role of such biomarkers of invasion should allow better delineation of tumour margins, which should improve treatment planning (especially surgery and radiotherapy) and provide information on the invasiveness of an individual tumour to help select the most appropriate therapy and help stratify patients for clinical trials.

  11. A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy.

    PubMed

    Winslow, Timothy B; Eranki, Annu; Ullas, Soumya; Singh, Anurag K; Repasky, Elizabeth A; Sen, Arindam

    2015-01-01

    The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy.

  12. A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy

    PubMed Central

    Winslow, Timothy B.; Eranki, Annu; Ullas, Soumya; Singh, Anurag K.; Repasky, Elizabeth A.; Sen, Arindam

    2015-01-01

    Purpose The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. Materials and methods SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. Results Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. Conclusions Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy. PMID:25986432

  13. Uterine Tumour Resembling Ovarian Sex Cord Tumour- A Rare Entity

    PubMed Central

    Ilhan, Tolgay Tuyan; Gül, Ayhan; Ugurluoglu, Ceyhan; Çelik, Çetin

    2016-01-01

    Uterine Tumour Resembling Ovarian Sex-Cord Tumours (UTROSCTs) are an extremely rare type of uterine body tumours arising from the endometrial stroma. Epidemiology, aetiology, pathogenesis, management and natural history of UTROSCTs are still a question of debate, as there is little available data in the literature. Although rare, the possibility of UTROSCTs should be kept in mind, when a patient presents with abnormal bleeding and an enlarged uterus. UTROSCTs appear dirty white/cream-coloured, gelatinous, well-circumscribed mass with smooth surface on macroscopic examination. We present a rare case of endometrial stromal tumour with sex-cord-like differentiation which was successfully treated by hysterectomy with bilateral salpingo-oophorectomy. The clinical manifestations, pathologic characteristics, diagnosis and management of these tumours are reviewed here. PMID:28208949

  14. Shear wave elastography of tumour growth in a human breast cancer model with pathological correlation.

    PubMed

    Chamming's, Foucauld; Latorre-Ossa, H; Le Frère-Belda, M A; Fitoussi, V; Quibel, T; Assayag, F; Marangoni, E; Autret, G; Balvay, D; Pidial, L; Gennisson, J L; Tanter, M; Cuenod, C A; Clément, O; Fournier, L S

    2013-08-01

    To assess stiffness in a human breast cancer implanted in mice using shear wave elastography (SWE) during tumour growth and to correlate the results with pathology. Local ethics committee for animal research approval was obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24 athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours, every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven tumours were measured both in vivo and ex vivo. Tumours of different sizes were removed for pathological analysis on which the percentages of viable cellular tissue, fibrosis and necrosis were measured. A total of 63 SWE measurements were performed. Stiffness increased during tumour growth with an excellent correlation with size (r = 0.94, P < 0.0001). No differences were found between the values of stiffness in vivo and ex vivo (P = 0.81). There was a significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant correlation with cellular tissue (r = 0.40, p = 0.1). Fibrosis plays an important role in stiffness as measured by SWE, whereas necrosis is correlated with softness. • In a breast cancer model, ultrasound tumour stiffness is correlated with size. • Stiffness changes with tumour growth are correlated with pathological changes. • Stiffness is very well correlated with proportion of tumour fibrosis. • Stiffness is inversely correlated with proportion of tumour necrosis. • Tumour stiffness measurements are similar in vivo and ex vivo.

  15. Giant cell tumour of the mandibular condyle.

    PubMed

    Della Sala, S W; Recla, M; Campolongo, F; Bortot, G; Bauer, M; Peterlongo, P

    1996-01-01

    The authors report a case of giant cell tumour of the mandibular condyle, which is a rare finding. This tumour, studied using the main three radiological modalities (plain radiography, CT and MRI) showed characteristic radiological features of "giant cell tumour".

  16. Adapting radiotherapy to hypoxic tumours

    NASA Astrophysics Data System (ADS)

    Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

    2006-10-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

  17. Intraspinal tumours in the Kenya African.

    PubMed

    Ruberti, R F; Carmagnani, A L

    1976-06-01

    Thirty-one cases of intraspinal tumours in the African have been described, with age, sex incidence, frequency, site and histopathology shown. Intraspinal tumours in this series are compared with the larger series. Extradural and intramedullary tumours together with cervical spine tumours appear to be more frequent in this series. There is a high incidence of dumbell tumours in the neurinomas. Sarcomas are the most common type of tumours and mainly affect the thoracic spine.

  18. Sclerostin expression in bone tumours and tumour-like lesions.

    PubMed

    Inagaki, Yusuke; Hookway, Edward S; Kashima, Takeshi G; Munemoto, Mitsuru; Tanaka, Yasuhito; Hassan, Andrew Bassim; Oppermann, Udo; Athanasou, Nick A

    2016-09-01

    To assess the immunophenotypic and mRNA expression of sclerostin in human skeletal tissues and in a wide range of benign and malignant bone tumours and tumour-like lesions. Sclerostin expression was evaluated by immunohistochemistry and quantitative polymerase chain reaction (PCR). In lamellar and woven bone, there was strong sclerostin expression by osteocytes. Osteoblasts and other cell types in bone were negative. Hypertrophic chondrocytes in the growth plate and mineralized cartilage cells in zone 4 of hyaline articular cartilage strongly expressed sclerostin, but most chondrocytes in hyaline cartilage were negative. In primary bone-forming tumours, including osteosarcomas, there was patchy expression of sclerostin in mineralized osteoid and bone. Sclerostin staining was seen in woven bone in fibrous dysplasia, in osteofibrous dysplasia, and in reactive bone formed in fracture callus, in myositis ossificans, and in the wall of solitary bone cysts and aneurysmal bone cysts. Sclerostin was expressed by hypertrophic chondrocytes in osteochondroma and chondroblasts in chondroblastoma, but not by tumour cells in other bone tumours, including myeloma and metastatic carcinoma. mRNA expression of sclerostin was identified by quantitative PCR in osteosarcoma specimens and cell lines. Sclerostin is an osteocyte marker that is strongly expressed in human woven and lamellar bone and mineralizing chondrocytes. This makes it a useful marker with which to identify benign and malignant osteogenic tumours and mineralizing cartilage tumours, such as chondroblastomas and other lesions in which there is bone formation. © 2016 John Wiley & Sons Ltd.

  19. Benign hepatic tumours and tumour like conditions in men.

    PubMed Central

    Karhunen, P J

    1986-01-01

    In a consecutive medicolegal necropsy series benign hepatic tumours and tumour like conditions occurred in 52% of the 95 men aged 35-69 years. The incidence increased with age, mainly due to small bile duct tumours (n = 26; mean age 56.7 years; p less than 0.01; mean size 1.3 mm). The next most common tumours were cavernous hemangiomas (n = 19; mean age 53.9 years; mean size 5.2 mm) that were not related to age. Focal nodular hyperplasia (n = 3; mean size 8.0 mm) tended to occur in a younger age group (mean age 40.3 years; p less than 0.001). Multiple bile duct tumours were present in 46% and hemangiomas in 50% of the men studied. Liver cell adenoma, nodular regenerative hyperplasia, and peliosis hepatis were incidental findings (one case of each). Nodular regenerative hyperplasia was associated with the consumption of alcohol and a total dose of 21.5 g of testosterone. These results indicate that benign hepatic tumours and tumour like conditions are not rare in men but may remain undetected because of their small size. Images PMID:3950039

  20. 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. © 2015 FEBS.

  1. 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

  2. Dental Implants.

    PubMed

    Zohrabian, Vahe M; Sonick, Michael; Hwang, Debby; Abrahams, James J

    2015-10-01

    Dental implants restore function to near normal in partially or completely edentulous patients. A root-form implant is the most frequently used type of dental implant today. The basis for dental implants is osseointegration, in which osteoblasts grow and directly integrate with the surface of titanium posts surgically embedded into the jaw. Radiologic assessment is critical in the preoperative evaluation of the dental implant patient, as the exact height, width, and contour of the alveolar ridge must be determined. Moreover, the precise locations of the maxillary sinuses and mandibular canals, as well as their relationships to the site of implant surgery must be ascertained. As such, radiologists must be familiar with implant design and surgical placement, as well as augmentation procedures utilized in those patients with insufficient bone in the maxilla and mandible to support dental implants.

  3. Penile Implants

    MedlinePlus

    ... Three-piece inflatable implants use a fluid-filled reservoir implanted under the abdominal wall, a pump and ... an erection, you pump the fluid from the reservoir into the cylinders. Afterward, you release the valve ...

  4. Diagnostics of neuroendocrine tumours.

    PubMed

    Hodolic, M; Fettich, J; Banti, E; Chondrogiannis, S; Al-Nahhas, A; Rubello, D

    2010-01-01

    Neuroendocrine tumours (NETs) are rare pathologies which origin from neuroectodermic and endodermic cells and that can produce peptides and amino acids. About 70% of NETs derive from gastroenterohepatic (GEP) system and the other 30% from the different sites through the body. They are distinguished into single and multiple localizations and also into sporadic, familial multiple endocrine-related forms and recurrent forms. Moreover, when they produce hormones they usually are symptomatic; yet, they are characterized by the synthesis and secretion in the blood stream of several tumor-specific markers or can express somatostatin receptors in their cellular surface. The diagnosis and follow-up of NETs rely on laboratory studies, histopathology and the combination of anatomical and functional imaging, with the latter being the main method for monitoring response to therapy. In recent years, nuclear medicine has contributed to the impressive development of the knowledge of NETs in terms of biology (receptor scintigraphy), pharmacology (development of new tracers) and therapy (radiometabolic therapy). Nuclear medicine procedures for diagnosis and treatment of NETs are based on the biological properties of these tumours: the expression of somatostatin receptors. Somatostatin receptor scintigraphy not only has a crucial role in diagnosis and staging of NETs, but also in assessing suitability for treatment with cold and radiolabelled somatostatin analogues, as well as in monitoring response to treatment and detecting recurrent disease. In conventional nuclear medicine, the two most important functional imaging modalities are ¹¹¹In-octrescan and ¹²³I-MIBG. Over the last 5 years, due to the development of new tracers, such as ⁶⁸Ga labelled-DOTA-peptides PET and ¹⁸F-DOPA, PET has also been employed with significant benefits in the diagnosis and management of NETs.

  5. Changes in blood metabolic parameters during the development of Walker-256 tumour-induced cachexia in rats are not caused by decreased food intake.

    PubMed

    Cassolla, Priscila; Moreira, Carolina Campos Lima; Liboni, Thaís Fernanda; Zaia, Cássia Thaïs Bussamra Vieira; Borba-Murad, Glaucia Regina; Bazotte, Roberto Barbosa; de Souza, Helenir Medri

    2012-06-01

    Blood metabolic parameters of Walker-256 tumour-bearing rats, on days 5, 8, 11 and 14 after implantation of tumour, were compared with those of rats without tumour fed ad libitum (free-fed control) or with reduced feeding (pair-fed control), similar to the anorexic tumour-bearing rats. Cachexia parameters and tumour mass also were investigated. In general, especially on day 14 after implantation of tumour, there was reduction of body mass, gastrocnemius muscle mass, food intake and glycemia and increase of blood triacylglycerol, free fatty acids, lactate and urea, compared with free-fed controls rats. These changes did not occur in pair-fed control, except a slight reduction of glycemia. Pair-fed control showed no significant changes in blood cholesterol and glycerol in comparison with free-fed control, although there was reduction of cholesterol and increase of blood glycerol on day 14 after tumour implantation compared with pair-fed control. The results demonstrate that, besides the characteristic signs of the cachexia syndrome such as anorexia, weight loss and muscle catabolism, Walker-256 tumour-bearing rats show several blood metabolic alterations, some of which begin as early as day 5 after implantation of tumour, and are accentuated during the development of cachexia. Evidence that the alterations of blood metabolic parameters of tumour-bearing rats were not found in pair-fed control indicate that they were not caused by decreased food intake. These changes were probably mediated by factors produced by tumour or host tissue in response to the presence of tumour.

  6. Combination of bacteriolytic therapy with magnetic field for Ehrlich tumour treatment.

    PubMed

    Ali, Fadel M; El-Gebaly, Reem H; Hamad, Amany M

    2017-07-01

    Referable to the limited response of the current available cancer treatment modalities, new effective cancer fighting treatments are needed. This work investigates the efficiency of intratumoural injection of Pseudomonas aeruginosa bacteria combined with a local tumour exposure to extremely low frequency square pulsed magnetic field (ELF SPMF) in the mouse Ehrlich tumour. 64 Ehrlich ascites tumour-implanted female albino BALB/C mice were equally split up into 4 groups. Group 1 (GP1) was the positive control group. Group 2 (GP2) received a single intratumoural injection of P. aeruginosa bacteria. Group 3 (GP3) was exposed to ELF SPMF for tumour local exposure. Group 4 (GP4) was treated with P. aeruginosa intratumoural injection followed by local exposure of the tumour to ELF SPMF. Treatment monitoring was evaluated using ultrastructural examination, flow cytometry analysis in addition to the measurement of tumour dielectric properties. Tumour cell apoptosis was obvious in GP2 and GP4, but, with higher severity and percentages in GP2. Tumour biophysical properties revealed a significant increase in static conductivity σS of GP2, and decreases in dielectric increment Δɛ´of both GP2 and GP4 compared to the GP1. Unfortunately, GP2 mice showed severe signs of toxicity. We advocate the utilization of the combination of P. aeruginosa and SPMF to yield the most effective antitumour agent with less bacteria-related toxicity.

  7. 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

  8. Murine Bioluminescent Hepatic Tumour Model

    PubMed Central

    Rajendran, Simon; Salwa, Slawomir; Gao, Xuefeng; Tabirca, Sabin; O'Hanlon, Deirdre; O'Sullivan, Gerald C.; Tangney, Mark

    2010-01-01

    This video describes the establishment of liver metastases in a mouse model that can be subsequently analysed by bioluminescent imaging. Tumour cells are administered specifically to the liver to induce a localised liver tumour, via mobilisation of the spleen and splitting into two, leaving intact the vascular pedicle for each half of the spleen. Lewis lung carcinoma cells that constitutively express the firefly luciferase gene (luc1) are inoculated into one hemi-spleen which is then resected 10 minutes later. The other hemi-spleen is left intact and returned to the abdomen. Liver tumour growth can be monitored by bioluminescence imaging using the IVIS whole body imaging system. Quantitative imaging of tumour growth using IVIS provides precise quantitation of viable tumour cells. Tumour cell death and necrosis due to drug treatment is indicated early by a reduction in the bioluminescent signal. This mouse model allows for investigating the mechanisms underlying metastatic tumour-cell survival and growth and can be used for the evaluation of therapeutics of liver metastasis. PMID:20689502

  9. [SDHB expression in Warthin's tumour].

    PubMed

    Vera-Sirera, Beatriz; Pérez-Rojas, Judith; López-Valdivia, Cecilia; Jiménez, Enrique; Collado-Martín, Diego; Vera-Sempere, Francisco

    2011-01-01

    Succinic dehydrogenase subunit B (SDHB) is an enzyme belonging to the mitochondrial complex II. The aim of this study is to analyse SDHB expression in a series of Warthin's tumours, studying its relationship with oncocytic changes, constantly present in this form of tumour. In resection tumour specimens from a series of ten Warthin's tumours (all from the parotid gland), immunohistochemical expression of SDHB was analysed using a commercially-available monoclonal antibody. The Warthin's tumours studied affected 10 men (mean age: 64.2 yrs, range 40-80), all with smoking habits, and 2 with metachronous bilateral involvement. Two patients presented associated urothelial carcinoma. Our SDHB study showed marked reactivity (++/+++) in all cases in the oncocytic epithelial component and also in striated duct cytoplasm (+) from non-tumorous parotid tissue. Expression was not influenced by age, smoking intensity or bilateral character. One of the tumours showed squamous metaplasia foci with SDHB-negativity at this level. Due to the constant and intense SDHB reactivity in oncocytic cells in our observations, oncocytic changes are not considered to be associated with defective enzyme activity in the mitochondrial complex II. Strong SDHB reactivity is an additional marker of oncocytic changes in Warthin's tumour. Neither of these facts has been described previously. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  10. Imaging characteristics of pleural tumours.

    PubMed

    De Paoli, Luca; Quaia, Emilio; Poillucci, Gabriele; Gennari, Antonio; Cova, Maria Assunta

    2015-12-01

    Malignant mesothelioma is doubtless the more known pleural tumour. However, according to the morphology code of the International Classification of Diseases for Oncology (ICD-O), there are several histological types of pleural neoplasms, divided into mesothelial, mesenchymal and lymphoproliferative tumours, that may be misdiagnosed. In this paper we summarise and illustrate the incidence aspects and the clinical, pathological and radiological features of these neoplasms. • According to the ICD-O, there are 11 different histological types of pleural neoplasm. • Imaging, clinical and histopathological aspects of these neoplasms may be overlapping. • Knowledge of different pleural tumours plays an important role for diagnosis orientation.

  11. Tumours of the nasal cavity*

    PubMed Central

    Stünzi, H.; Hauser, B.

    1976-01-01

    Tumours of the nasal cavity are rare in domestic animals, most cases occurring in the dog. Epithelial tumours are the most common type in carnivores (dogs and cats). In general, the same types of tumour occur in domestic animals as occur in man. There was no significant predisposition for breed in dogs, but in both dogs and cats far more males than females were affected. Metastases occurred only rarely. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 9Fig. 10Fig. 11Fig. 12Fig. 5Fig. 6Fig. 7Fig. 8 PMID:1086156

  12. Microenvironmental regulation of tumour angiogenesis.

    PubMed

    De Palma, Michele; Biziato, Daniela; Petrova, Tatiana V

    2017-08-01

    Tumours display considerable variation in the patterning and properties of angiogenic blood vessels, as well as in their responses to anti-angiogenic therapy. Angiogenic programming of neoplastic tissue is a multidimensional process regulated by cancer cells in concert with a variety of tumour-associated stromal cells and their bioactive products, which encompass cytokines and growth factors, the extracellular matrix and secreted microvesicles. In this Review, we discuss the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.

  13. 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.

  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. Primitive neuroectodermal adrenal gland tumour.

    PubMed

    Tsang, Y P; Lang, Brian H H; Tam, S C; Wong, K P

    2014-10-01

    Ewing's sarcoma, also called primitive neuroectodermal tumour of the adrenal gland, is extremely rare. Only a few cases have been reported in the literature. We report on a woman with adult-onset primitive neuroectodermal tumour of the adrenal gland presenting with progressive flank pain. Computed tomography confirmed an adrenal tumour with invasion of the left diaphragm and kidney. Radical surgery was performed and the pain completely resolved; histology confirmed the presence of primitive neuroectodermal tumour, for which she was given chemotherapy. The clinical presentation of this condition is non-specific, and a definitive diagnosis is based on a combination of histology, as well as immunohistochemical and cytogenic analysis. According to the literature, these tumours demonstrate rapid growth and aggressive behaviour but there are no well-established guidelines or treatment strategies. Nevertheless, surgery remains the mainstay of local disease control; curative surgery can be performed in most patients. Adjuvant chemoirradiation has been advocated yet no consensus is available. The prognosis of patients with primitive neuroectodermal tumours remains poor.

  16. Specific antitumour immunity of HIFU-activated cytotoxic T lymphocytes after adoptive transfusion in tumour-bearing mice.

    PubMed

    Ran, Li-Feng; Xie, Xun-Peng; Xia, Ji-Zhu; Xie, Fang-Lin; Fan, Yan-Min; Wu, Feng

    2016-01-01

    The aim of this study was to investigate the specific anti-tumour immunity of cytotoxic T lymphocytes (CTL) activated by high-intensity focused ultrasound (HIFU) after adoptive transfer in a murine tumour model. H22 tumour-bearing mice were treated by either HIFU or sham-HIFU, while naïve syngeneic mice were used as controls. They were sacrificed and the spleens were harvested 14 days after HIFU. T lymphocytes were obtained from the spleens, and then adoptively transferred into 40 mice each bearing a 3-day implanted H22 tumour. On day 14 after adoptive transfer, 10 mice were sacrificed in each group for assessment of the number of tumour-infiltrating T lymphocytes and interferon-gamma (IFN-γ) secreting cells. The remaining 30 mice were continuously observed for 60 days, and tumour growth, progression and survival were recorded. HIFU significantly increased peripheral blood CD3(+), CD4(+) levels and CD4(+)/CD8(+) ratio (P < 0.05), CTL cytotoxicity (P < 0.01) and IFN-γ and TNF-α secretion (P < 0.01) in H22 tumour-bearing mice. Adoptive transfer of HIFU-activated T lymphocytes into the autologous tumour-bearing mice induced a significant increase of tumour-infiltrating T lymphocytes and IFN-γ-secreting cells (P < 0.001). Compared to the control and sham-HIFU groups, HIFU-activated lymphocytes elicited significant inhibition of in vivo tumour growth (P < 0.01) and progression (P < 0.0001), and longer survival time in the tumour-bearing mice (P < 0.001). HIFU could enhance CTL's specific antitumour immunity. Adoptive transfer of HIFU-activated T lymphocytes could increase local antitumour immunity, and elicit stronger inhibition on tumour growth and progression, with more survival benefit in the autologous tumour-bearing mice.

  17. 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. PMID:27879873

  18. 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.

  19. Microsatellite instability in thyroid tumours and tumour-like lesions

    PubMed Central

    Lazzereschi, D; Palmirotta, R; Ranieri, A; Ottini, L; Verì, M C; Cama, A; Cetta, F; Nardi, F; Colletta, G; Mariani-Costantini, R

    1999-01-01

    Fifty-one thyroid tumours and tumour-like lesions were analysed for instability at ten dinucleotide microsatellite loci and at two coding mononucleotide repeats within the transforming growth factor β (TGF-β) type II receptor (TβRII) and insulin-like growth factor II (IGF-II) receptor (IGFIIR) genes respectively. Microsatellite instability (MI) was detected in 11 out of 51 cases (21.5%), including six (11.7%) with MI at one or two loci and five (9.8%) with Ml at three or more loci (RER+ phenotype). No mutations in the TβRII and IGFIIR repeats were observed. The overall frequency of MI did not significantly vary in relation to age, gender, benign versus malignant status and tumour size. However, widespread MI was significantly more frequent in follicular adenomas and carcinomas than in papillary and Hürthle cell tumours: three out of nine tumours of follicular type (33.3%) resulted in replication error positive (RER+), versus 1 out of 29 papillary carcinomas (3.4%, P = 0.01), and zero out of eight Hürthle cell neoplasms. Regional lymph node metastases were present in five MI-negative primary cancers and resulted in MI-positive in two cases. © 1999 Cancer Research Campaign PMID:9888478

  20. 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

  1. Endodontic implants

    PubMed Central

    Yadav, Rakesh K.; Tikku, A. P.; Chandra, Anil; Wadhwani, K. K.; Ashutosh kr; Singh, Mayank

    2014-01-01

    Endodontic implants were introduced back in 1960. Endodontic implants enjoyed few successes and many failures. Various reasons for failures include improper case selection, improper use of materials and sealers and poor preparation for implants. Proper case selection had given remarkable long-term success. Two different cases are being presented here, which have been treated successfully with endodontic implants and mineral trioxide aggregate Fillapex (Andreaus, Brazil), an MTA based sealer. We suggest that carefully selected cases can give a higher success rate and this method should be considered as one of the treatment modalities. PMID:25298723

  2. Vasoproliferative tumours of the retina

    PubMed Central

    Heimann, H.; Bornfeld, N.; Vij, O.; Coupland, S.; Bechrakis, N.; Kellner, U.; Foerster, M.

    2000-01-01

    BACKGROUND—Vasoproliferative tumours of the retina (VPTR) are benign tumours of unknown origin, occurring mostly in otherwise healthy patients. VPTR may be associated with other chorioretinal diseases, such as uveitis. The tumours, which histologically represent reactive gliovascular proliferations, are characterised by a pink to yellow appearance on funduscopy and are accompanied by exudative and haemorrhagic changes of the retina.
METHODS—22 cases of VPTR in 21 patients were examined with a follow up period between 1 month and 6 years. Ophthalmological changes associated with VPTR were intraretinal and subretinal exudations (n=18), exudative detachments of the surrounding sensory retina (n=13), intraretinal and subretinal haemorrhages (n=10), exudative changes within the macula (n=10), hyperpigmentation of the retinal pigment epithelium at the border of the exudative retinal changes (n=9), and vitreous haemorrhages (n=4). Tumour biopsy was performed in two cases. Treatment consisted of plaque radiotherapy (n=14), plaque radiotherapy and cryotherapy (two), cryotherapy only (two), observation (three), and enucleation in one case of a blind and painful eye.
RESULTS—Regression of the tumour and the associated exudative changes could be observed in all treated cases. Visual acuity at last follow up improved two lines or more in two cases, remained within two lines of the initial visual acuity in 15 cases, and worsened in the remaining five. Histopathological examination of the biopsy specimens and the tumour of the enucleated eye showed massive capillary proliferation with perivascular spindle-shaped glial cells of retinal origin.
CONCLUSION—The correct diagnosis of VPTR is of importance as these lesions may lead to visual loss. Further, VPTR must be differentiated from angiomas associated with von Hippel-Lindau disease as well as from ocular and systemic malignancies. Regression of tumour thickness and associated retinal changes can be achieved with

  3. Multiple tumours in survival estimates.

    PubMed

    Rosso, Stefano; De Angelis, Roberta; Ciccolallo, Laura; Carrani, Eugenio; Soerjomataram, Isabelle; Grande, Enrico; Zigon, Giulia; Brenner, Hermann

    2009-04-01

    In international comparisons of cancer registry based survival it is common practice to restrict the analysis to first primary tumours and exclude multiple cancers. The probability of correctly detecting subsequent cancers depends on the registry's running time, which results in different proportions of excluded patients and may lead to biased comparisons. We evaluated the impact on the age-standardised relative survival estimates of also including multiple primary tumours. Data from 2,919,023 malignant cancers from 69 European cancer registries participating in the EUROCARE-4 collaborative study were used. A total of 183,683 multiple primary tumours were found, with an overall proportion of 6.3% over all the considered cancers, ranging from 0.4% (Naples, Italy) to 12.9% (Iceland). The proportion of multiple tumours varied greatly by type of tumour, being higher for those with high incidence and long survival (breast, prostate and colon-rectum). Five-year relative survival was lower when including patients with multiple cancers. For all cancers combined the average difference was -0.4 percentage points in women and -0.7 percentage points in men, and was greater for older registries. Inclusion of multiple tumours led to lower survival in 44 out of 45 cancer sites analysed, with the greatest differences found for larynx (-1.9%), oropharynx (-1.5%), and penis (-1.3%). Including multiple primary tumours in survival estimates for international comparison is advisable because it reduces the bias due to different observation periods, age, registration quality and completeness of registration. The general effect of inclusion is to reduce survival estimates by a variable amount depending on the proportion of multiple primaries and cancer site.

  4. Corpectomy of three cervical vertebral bodies for malignant tumours--a study of two cases.

    PubMed

    Guzik, Grzegorz

    2013-01-01

    The increased detection rate of spinal tumours is due to more precise methods used for imaging the spinal column and better survival of cancer patients. It is therefore associated with greater incidence of metastatic complications. Primary tumours of the spine, both malignant and benign, are very rare. Histopathological confirmation is a prerequisite of correct treatment. Two patients with pain in the neck area, progressive paresis, breathing disorders and dysphagia were admitted to our hospital. In the first patient, a 78-year-old woman, imaging examinations revealed a large exophytic tumour originating from C5-C7 vertebrae and compressing other neck structures. In view of the progressive paresis and dyspnoea, we decided to perform surgical resection of the tumour without a prior biopsy. We used the Southwick and Robinson approach on the right side and the tumour was removed together with damaged vertebral bodies, which were replaced by an implant. The next stage of the treatment involved stabilisation of the spine from C3 to Th2. Histopathological evaluation confirmed a diagnosis of chordoma. The second patient was a 73-year-old man. Imaging examinations revealed destruction of the C6 to Th1 vertebral bodies by a tumour with pathological fractures and compression of the spinal canal. The tumour was approached from the left side and removed according to the method presented by Southwick and Robinson. The removed vertebral bodies were replaced with implants. The spine was stabilised in the second stage of treatment. A diagnosis of metastatic adenocarcinoma was confirmed by a histopathological examination. Tumours located in the cervical spine, especially at the C7-Th1 level, cause considerable diagnostic and therapeutic problems. Southwick and Robinson's anterior approach allows for good exposure of vertebral bodies down to the Th2 level.

  5. 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

  6. Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study.

    PubMed

    Nijsen, F; Rook, D; Brandt, C; Meijer, R; Dullens, H; Zonnenberg, B; de Klerk, J; van Rijk, P; Hennink, W; van het Schip, F

    2001-06-01

    Intra-arterial administration of beta-emitting particles that become trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-microm poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was < or =0.1%ID/g, with incidental exceptions in the lungs and stomach. Very little 166Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6. 1+/-2.9 for rats with tumour (n=15) versus 0.7+/-0.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use of adrenaline. Histological analysis showed that five times as many large (>10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma.

  7. Growth studies of subcutaneous rat tumours: comparison of 31P-NMR spectroscopy, acid extracts and histology.

    PubMed

    Stubbs, M; Rodrigues, L M; Griffiths, J R

    1989-11-01

    31P-NMP, surface coil spectra of three subcutaneously implanted rat tumours (Morris hepatoma 7777, GH3 prolactinoma, Walker carcinosarcoma) and an N-methyl-N-nitrosourea induced rat mammary adenocarcinoma at different stages of growth were obtained and compared with histological sections taken immediately after NMR acquisitions. Metabolite ratios (phosphocreatine (PCr)/beta nucleoside triphosphate (beta NTP), PCr/Pi, beta NTP/Pi) calculated from the NMR spectra were compared with ratios obtained from acid extracts of tumours of similar size. Measurements of creatine and ADP were also made. Three of the tumours showed positive correlations between increasing tumour size and decreasing metabolite ratios measured both by NMR and in extracts, whereas the Walker carcinosarcoma showed no correlation between size and any parameters measured. Phosphorus metabolite ratios, measured in extracts of skin overlying the tumours, indicated a fall in high energy phosphate when there was histological evidence of skin invasion by the tumour. Surface coil 31P-NMR spectra of subcutaneously grown or induced tumours in the rat represent a slowly changing steady state as the tumour increases in size. We conclude that increasing numbers of hypoxic tumour cells, rather than large areas of necrotic tissue, contribute largely to the NMR spectrum.

  8. Simulation study of pO2 distribution in induced tumour masses and normal tissues within a microcirculation environment.

    PubMed

    Li, Mao; Li, Yan; Wen, Peng Paul

    2014-01-01

    The biological microenvironment is interrupted when tumour masses are introduced because of the strong competition for oxygen. During the period of avascular growth of tumours, capillaries that existed play a crucial role in supplying oxygen to both tumourous and healthy cells. Due to limitations of oxygen supply from capillaries, healthy cells have to compete for oxygen with tumourous cells. In this study, an improved Krogh's cylinder model which is more realistic than the previously reported assumption that oxygen is homogeneously distributed in a microenvironment, is proposed to describe the process of the oxygen diffusion from a capillary to its surrounding environment. The capillary wall permeability is also taken into account. The simulation study is conducted and the results show that when tumour masses are implanted at the upstream part of a capillary and followed by normal tissues, the whole normal tissues suffer from hypoxia. In contrast, when normal tissues are ahead of tumour masses, their pO2 is sufficient. In both situations, the pO2 in the whole normal tissues drops significantly due to the axial diffusion at the interface of normal tissues and tumourous cells. As the existence of the axial oxygen diffusion cannot supply the whole tumour masses, only these tumourous cells that are near the interface can be partially supplied, and have a small chance to survive.

  9. Tumour banking: the Spanish design.

    PubMed

    Morente, M M; de Alava, E; Fernandez, P L

    2007-01-01

    In the last decade the technical advances in high throughput techniques to analyze DNA, RNA and proteins have had a potential major impact on prevention, diagnosis, prognosis and treatment of many human diseases. Key pieces in this process, mainly thinking about the future, are tumour banks and tumour bank networks. To face these challenges, diverse suitable models and designs can be developed. The current article presents the development of a nationwide design of tumour banks in Spain based on a network of networks, specially focusing on its harmonization efforts mainly regarding technical procedures, ethical requirements, unified quality control policy and unique sample identification. We also describe our most important goals for the next years. This model does not correspond to a central tumour bank, but to a cooperative and coordinated network of national and regional networks. Independently from the network in which it is included, sample collections reside in their original institution, where it can be used for further clinical diagnosis, teaching and research activities of each independent hospital. The herein described 'network of networks' functional model could be useful for other countries and/or international tumour bank activities.

  10. 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

  11. Pitfalls in colour photography of choroidal tumours.

    PubMed

    Schalenbourg, A; Zografos, L

    2013-02-01

    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.

  12. Multifocal multi-site Warthin tumour.

    PubMed

    Hilton, Jennifer M; Phillips, John S; Hellquist, Henrik B; Premachandra, Don J

    2008-12-01

    The unique case of a 55-year-old man with multifocal adenolymphoma (Warthin's tumour) of both parotid glands, the neck and post-nasal space is presented. Warthin tumour is almost exclusively a parotid tumour but is known to be bilateral in 7-10% of cases and multifocal in 2% of cases. Most extraglandular Warthin tumours have been located in neck lymph nodes and only a few cases have been reported from other sites. The presented case is unique in having synchronous and metachronous Warthin tumours, as well as one of the tumours being neither truly parotid, nor within a lymph node.

  13. Tumour-associated eosinophilia in the bladder.

    PubMed Central

    Lowe, D; Fletcher, C D; Gower, R L

    1984-01-01

    Tumour eosinophilia is an uncommon but striking phenomenon which has been found in many tumours, mostly of large cell type or squamous differentiation. The incidence, appearance and importance of tumour eosinophilia in the bladder are described. Eosinophilia is commoner in deeply invasive tumours and in tumours showing squamous metaplasia. Transitional cell carcinomas with eosinophilia have a better prognosis than those without, but this improvement is not seen in squamous cell carcinomas of the bladder. When eosinophilia is found on superficial biopsies of a bladder tumour, the possibility of muscle invasion should be considered. PMID:6725595

  14. PHD2 in tumour angiogenesis

    PubMed Central

    Chan, D A; Giaccia, A J

    2010-01-01

    Originally identified as the enzymes responsible for catalysing the oxidation of specific, conserved proline residues within hypoxia-inducible factor-1α (HIF-1α), the additional roles for the prolyl hydroxylase domain (PHD) proteins have remained elusive. Of the four identified PHD enzymes, PHD2 is considered to be the key oxygen sensor, as knockdown of PHD2 results in elevated HIF protein. Several recent studies have highlighted the importance of PHD2 in tumourigenesis. However, there is conflicting evidence as to the exact role of PHD2 in tumour angiogenesis. The divergence seems to be because of the contribution of stromal-derived PHD2, and in particular the involvement of endothelial cells, vs tumour-derived PHD2. This review summarises our current understanding of PHD2 and tumour angiogenesis, focusing on the influences of PHD2 on vascular normalisation and neovascularisation. PMID:20461086

  15. Melanotic neuroectodermal tumour of infancy.

    PubMed

    Siddiqui, T H; Amin, M R; Bashar, M A; Ahmed, Z; Matin, A; Hasan, G Z; Islam, M D; Hossain, M Z

    2011-04-01

    Melanotic neuroectodermal tumour in infancy is rare, mainly benign with little tendency to recur after excision or effective curettage. This pigmented neoplasm of neural crest origin occurring in infants before 1 year of age. The most common site of occurrence is the anterior maxillary alveolar ridge (70%), following by the skull, brain and mandible. The genital organ is the most frequent extra cranial site. We report a 6 months old male baby with a similar tumour arising from right half of cheek involving the maxilla. We diagnosed the case after histological report. We remove the tumour through a sub-labial incision. The mass was blackish in colour, and was mobilized from all side including from the maxillary sinuses. The author thought that this should be reported for improving the clinical awareness and treatment of pigmented soft tissue mass in children. Almost one year follow up of the patients showed no recurrence.

  16. Tumour markers in breast cancer.

    PubMed Central

    Cove, D. H.; Woods, K. L.; Smith, S. C.; Burnett, D.; Leonard, J.; Grieve, R. J.; Howell, A.

    1979-01-01

    The clinical usefulness of 8 potential tumour markers has been evaluated in 69 patients with Stage I and II breast cancer and 57 patients with Stage III and IV. Serum CEA concentrations were raised in 13% of patients with local and 65% of those with advanced breast cancer. In patients with clinical evidence of progression or regression of tumour, serum CEA levels changed appropriately in 83% of cases. Taking 4 of the markers (carcinoembryonic antigen (CEA), lactalbumin, alpha subunit and haptoglobin) serum concentrations of one or more were raised in 33% of patients with local disease and 81% of those with advanced breast cancer. However, marker concentrations were often only marginally raised, and are unlikely to provide sensitive guide to tumour burden. CEA, lactalbumin and alpha subunit were detectable in 68%, 43% and 40% respectively of extracts of primary breast cancers. PMID:92331

  17. About Implantable Contraception

    MedlinePlus

    ... TV, Video Games, and the Internet About Implantable Contraception KidsHealth > For Parents > About Implantable Contraception Print A ... How Much Does It Cost? What Is Implantable Contraception? Implantable contraception (often called the birth control implant) ...

  18. High-risk gastrointestinal stromal tumour (GIST) and synovial sarcoma display similar angiogenic profiles: a nude mice xenograft study

    PubMed Central

    Giner, Francisco; Machado, Isidro; Lopez-Guerrero, Jose Antonio; Mayordomo-Aranda, Empar; Llombart-Bosch, Antonio

    2017-01-01

    Background Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract. Spindle cell monophasic synovial sarcoma (SS) can be morphologically similar. Angiogenesis is a major factor for tumour growth and metastasis. Our aim was to compare the angiogenic expression profiles of high-risk GIST and spindle cell monophasic SS by histological, immunohistochemical and molecular characterisation of the neovascularisation established between xenotransplanted tumours and the host during the initial phases of growth in nude mice. Methods The angiogenic profile of two xenotransplanted human soft-tissue tumours were evaluated in 15 passages in nude mice using tissue microarrays (TMA). Tumour pieces were also implanted subcutaneously on the backs of 14 athymic Balb-c nude mice. The animals were sacrificed at 24, 48, and 96 h; and 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularisation experiments). Results Morphological similarities were apparent in the early stages of neoplastic growth of these two soft-tissue tumours throughout the passages in nude mice and in the two neovascularisation experiments. Immunohistochemistry demonstrated overexpression of pro-angiogenic factors between 24 h and 96 h after xenotransplantation in both tumours. Additionally, neoplastic cells coexpressed chemokines (CXCL9, CXCL10, GRO, and CXCL12) and their receptors in both tumours. Molecular studies showed two expression profiles, revealing an early and a late phase in the angiogenic process. Conclusion This model could provide information on the early stages of the angiogenic process in monophasic spindle cell SS and high-risk GIST and offers an excellent way to study possible tumour response to antiangiogenic drugs. PMID:28386296

  19. Targeting aurora kinases limits tumour growth through DNA damage-mediated senescence and blockade of NF-κB impairs this drug-induced senescence

    PubMed Central

    Liu, Yan; Hawkins, Oriana E; Su, Yingjun; Vilgelm, Anna E; Sobolik, Tammy; Thu, Yee-Mon; Kantrow, Sara; Splittgerber, Ryan C; Short, Sarah; Amiri, Katayoun I; Ecsedy, Jeffery A; Sosman, Jeffery A; Kelley, Mark C; Richmond, Ann

    2013-01-01

    Oncogene-induced senescence can provide a protective mechanism against tumour progression. However, production of cytokines and growth factors by senescent cells may contribute to tumour development. Thus, it is unclear whether induction of senescence represents a viable therapeutic approach. Here, using a mouse model with orthotopic implantation of metastatic melanoma tumours taken from 19 patients, we observed that targeting aurora kinases with MLN8054/MLN8237 impaired mitosis, induced senescence and markedly blocked proliferation in patient tumour implants. Importantly, when a subset of tumour-bearing mice were monitored for tumour progression after pausing MLN8054 treatment, 50% of the tumours did not progress over a 12-month period. Mechanistic analyses revealed that inhibition of aurora kinases induced polyploidy and the ATM/Chk2 DNA damage response, which mediated senescence and a NF-κB-related, senescence-associated secretory phenotype (SASP). Blockade of IKKβ/NF-κB led to reversal of MLN8237-induced senescence and SASP. Results demonstrate that removal of senescent tumour cells by infiltrating myeloid cells is crucial for inhibition of tumour re-growth. Altogether, these data demonstrate that induction of senescence, coupled with immune surveillance, can limit melanoma growth. PMID:23180582

  20. Molecular radiotheranostics for neuroendocrine tumours.

    PubMed

    Navalkissoor, Shaunak; Flux, Glenn; Bomanji, Jamshed

    2017-10-01

    This article discusses the important role of nuclear medicine imaging and therapy in the management of neuroendocrine tumours (NETs). Somatostatin receptor scintigraphy has a high impact on patient management versus conventional imaging. Molecular radiotherapy is an important part of the management of patients with NETs. Selection of patients for molecular radiotherapy in NETs is based on uptake on their radionuclide imaging study. The imaging agent has the same mechanism of uptake as the therapeutic agent. Thus, the imaging study preselects patients that are likely to concentrate radiation within their tumours. © Royal College of Physicians 2017. All rights reserved.

  1. [Radionuclide therapy for neuroendocrine tumours].

    PubMed

    Mortensen, Jann; Oturai, Peter; Højgaard, Liselotte; Knigge, Ulrich; Hansen, Carsten Palnaes; Martiný, Lars; Rasmussen, Palle; Kjaer, Andreas

    2010-10-25

    Peptide receptor radionuclide therapy using somatostatin analogues labelled with beta-emitting isotopes can be given to patients with metastasized or inoperable neuroendocrine tumours provided these have increased uptake on octreotide scintigraphy. This is a brief review of the treatment principle, indications and contraindications and practices with (177)Lu-DOTATATE treatment used at Rigshospitalet. Side effects are generally mild and reversible. Severe long-term side effects are rare. The majority of patients will experience increased quality of life and partial tumour reduction or stabilization for a period of time. However, up to 20% will experience no treatment effect.

  2. Identification of human brain tumour initiating cells.

    PubMed

    Singh, Sheila K; Hawkins, Cynthia; Clarke, Ian D; Squire, Jeremy A; Bayani, Jane; Hide, Takuichiro; Henkelman, R Mark; Cusimano, Michael D; Dirks, Peter B

    2004-11-18

    The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 10(5) CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.

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

    PubMed

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

    2015-06-01

    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. © The Author (2015). Published by Oxford University Press on

  4. Radiofrequency ablation suppresses distant tumour growth in a novel rat model of multifocal hepatocellular carcinoma.

    PubMed

    Erös de Bethlenfalva-Hora, Caroline; Mertens, Joachim C; Piguet, Anne-Christine; Kettenbach, Joachim; Schmitt, Johannes; Terracciano, Luigi; Weimann, Rosemarie; Dufour, Jean-François; Geier, Andreas

    2014-02-01

    RFA (radiofrequency ablation) is an established therapy for HCC (hepatocellular carcinoma). The multikinase inhibitor sorafenib prolongs survival in advanced HCC. We examined the effects of RFA alone and in combination with sorafenib on a bystanding tumour in a two-tumour rat model of HCC. A total of 80 rats were implanted with two liver tumours and randomized to four treatment groups: vehicle and sham operation (control), sorafenib and sham operation (Sora/Sham), vehicle and RFA (Vh/RFA), and sorafenib and RFA (Sora/RFA) (n=10/group per time point). RFA or sham-operation was performed on the left lobe tumour on day 15. Animals were killed at day 18 and day 30. Non-RFA-targeted right lobe tumours were analysed for angiogenesis, growth factors [HGF (hepatocyte growth factor), EGF (epidermal growth factor) and VEGF (vascular endothelial growth factor)] and infiltrating immune cells (CD3 and CD68). At day 30, the non-RFA-targeted tumours were significantly smaller in all three treatment groups compared with control (Sora/Sham P≤0.0001, Vh/RFA P=0.005 and Sora/RFA P≤0.0001). The smallest tumours were observed in animals treated with a combination of sorafenib and RFA, whereas the size reduction seen in the RFA-only group indicated an RFA-mediated distant suppression of tumour growth. Growth factor measurement revealed transiently decreased EGF levels after RFA (P=0.008), whereas sorafenib treatment decreased HGF levels (P=0.001). MVD (microvessel density) was reduced by sorafenib (P=0.002) despite increased VEGF levels (P≤0.0001). The immune parameters revealed augmented T-cells and IL-10 (interleukin 10) levels in all three treatment groups; sorafenib additionally increased macrophage numbers (P≤0.0001). RFA and sorafenib alone resulted in significant volume reduction of the non-RFA-targeted tumour; this effect was enhanced when both modalities were combined.

  5. [Intestinal carcinoid tumour: Case report].

    PubMed

    Mussan-Chelminsky, Gil; Vidal-González, Pablo; Núñez-García, Edgar; Valencia-García, Luis César; Márquez-Ugalde, Miguel Ángel

    2015-01-01

    Carcinoid of the small intestine, is a well-differentiated neuroendocrine tumor that rarely presents with clinical signs. This tumour can be associated with other conditions, such as inflammatory bowel disease, presenting a wide range of symptoms. In some cases they have an aggressive and highly symptomatic behaviour; thus, clinical suspicion must be high to make an early diagnosis. A 60 year-old male patient with Crohn's disease and gastrointestinal symptoms attributed to this disease within the last year. He presented with intestinal obstruction initially treated with conservative management with no improvement. Exploratory laparotomy was performed finding a mesenteric tumour that caused the bowel obstruction. Bowel resection with primary anastomosis was performed. The pathology report showed an intestinal carcinoid tumour with lymph node metastases. The patient recovered well, and was discharged without complications to continue medical treatment and follow-up by the Oncology department. In almost 42% of the cases, the most common site of carcinoid tumours is the small intestine, and of these, 41% are presented as locoregional disease. Patients with Crohn's disease present a higher incidence. In these cases, the most common presentation is an acute intestinal obstruction (90%). Surgery is usually curative, and follow up is important as the symptoms of Crohn's disease can hide any recurrence. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  6. PET imaging in endocrine tumours.

    PubMed

    Khan, S; Lloyd, C; Szyszko, T; Win, Z; Rubello, D; Al-Nahhas, A

    2008-06-01

    The role of PET in the assessment of endocrine tumours has been, until recently, restricted to the use of (18)F-fluoro-deoxy-D-glucose ((18)F-FDG). Being a marker of metabolically active lesions that show high grading and low differentiation, FDG is not ideal for this purpose since the majority of endocrine tumours are slow growing and highly differentiated. It is however useful when dedifferentiation takes place and provides excellent prognostic information. A number of hormone precursors and amino acids are labelled with (11)C and used successfully in the management of parathyroid, adrenal and pituitary tumours. However, the short half-life of (11)C radiopharmaceuticals restricts their use to centres with access to an on-site cyclotron, while the high cost of production may limit their use to research purposes. A promising new positron-emission tomography (PET) tracer is Gallium-68 obtained by elution from a long shelf-life generator that makes it economic and cyclotron-independent. Its short half-life and flexible labelling ability to a wide range of peptides and antibodies makes it ideal for PET imaging. In addition to imaging GEP-NETs and phaeochromocytoma, it has the potential to be used in a wider range of endocrine tumours.

  7. Primary brain tumours in adults.

    PubMed

    Ricard, Damien; Idbaih, Ahmed; Ducray, François; Lahutte, Marion; Hoang-Xuan, Khê; Delattre, Jean-Yves

    2012-05-26

    Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.

  8. Tumour growth results in changes in placental amino acid transport in the rat: a tumour necrosis factor alpha-mediated effect.

    PubMed Central

    Carbó, N; López-Soriano, F J; Fiers, W; Argilés, J M

    1996-01-01

    The implantation of a fast growing tumour (Yoshida AH-130 ascites hepatoma) to late pregnant rats resulted in no changes in fetal growth, this possibly being associated with an important increase in the fetal uptake of maternal-derived amino acids [Carbó, López-Soriano and Argilés (1995) Endocrinology 136, 3579-3584]. The present investigation was undertaken to see whether the presence of the tumour induced changes in placental transport systems. For alanine transport, although no changes in affinity (Km) were observed, tumour growth resulted in a 192% increase in Vmax in the Na(+)-independent component. Kinetic analysis of the Na(+)-dependent component resulted in two clearly different components: while the low-affinity and high-capacity component was unaffected by tumour growth, the high-affinity, low-capacity component of the tumour-bearing rats showed an important increase in Vmax. (78%). With regard to leucine transport, tumour burden induced important increases in the Na(+)-independent component, not only in Km (262%) but also in Vmax. (189%). Since elevated tumour necrosis factor-alpha (TNF) concentrations have been reported in this kind of tumour model, we performed the same type of transport experiments in rats chronically treated with TNF, the results obtained showing great similarities with those observed with tumour growth. The Vmax. of Na(+)-independent alanine transport was also increased by the cytokine (104%) while no changes were observed in affinity. TNF treatment also induced an increase in the Vmax. (67%) of the Na(+)-dependent (high-affinity, low-capacity) component while no changes in affinity were observed. Concerning leucine kinetics, TNF treatment, as in the case of tumour growth, also increased Km (155%) and Vmax. (72%) associated with Na(+)-independent transport. Interestingly, treatment with the cytokine increased both the Km (43%) and Vmax. (64%) of the Na(+)-dependent component. The inhibition patterns suggest the existence of more

  9. Cochlear implant

    MedlinePlus

    ... bilateral cochlear implantation: a review. Curr Opin Otolaryngol Head Neck Surg . 2007;15(5):315-318. PMID: 17823546. ... BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. Philadelphia, PA: Elsevier Saunders; 2015: ...

  10. Histrelin Implant

    MedlinePlus

    ... implant (Supprelin LA) is used to treat central precocious puberty (CPP; a condition causing children to enter puberty too soon, resulting in faster than normal bone growth and development of sexual characteristics) in girls ...

  11. Breast Implants

    MedlinePlus

    ... in the United States: saline-filled and silicone gel-filled. Both types have a silicone outer shell. ... them. Provide information on saline-filled and silicone gel-filled breast implants, including data supporting a reasonable ...

  12. Radiobiological and Magnetic Resonance Studies of Combined Radiation and Cisplatin Therapy in the 9l Rat Brain Tumour Model.

    NASA Astrophysics Data System (ADS)

    Wilkins, David E.

    1993-01-01

    The prognosis for adult patients with primary malignant brain tumours is poor. Radiation therapy is a standard adjutant to surgery in the treatment of these patients, but is rarely curative. The extreme radio-resistance of primary malignant brain tumours is due in part to their enhanced capacity for repair of potentially lethal radiation damage. The chemotherapeutic agent cisplatin has been shown to inhibit repair of radiation damage. Therefore combined cisplatin and radiation therapy could be a key to enhanced therapeutic gain in the treatment of primary malignant brain tumours. In this project, the 9L rat brain tumour model was used to investigate combined radiation and cisplatin treatments. In vitro experiments showed the 9L cell line to be highly radioresistant and, like human malignant brain tumour cells, to have a high capacity for repair of potentially lethal radiation damage. These cells were found to be moderately resistant to the cytotoxic effects of cisplatin. In vitro exposure to cisplatin at clinically relevant concentrations caused inhibition of potentially lethal damage repair, with the amount of inhibition depending on cisplatin dose and treatment sequence. Magnetic resonance imaging (MRI) was used to monitor the effects of combined radiation and cisplatin treatments of implanted intracranial 9L tumours in rats. A new technique for implanting experimental tumours was developed which resulted in more uniform tumour growth, and methods for radiation and cisplatin treatment of experimental intracranial tumours were developed and evaluated. Non-invasive measurements of tumour size using MRI were found to correlate well with measurements made from histological sections. Intraperitoneal administration of gadolinium contrast agent immediately before T1-weighted MRI was shown to be the most accurate and reliable method for MRI measurement of intracranial tumour size. The capability of MRI to provide early indications of radiation injury to normal brain

  13. Cochlear implants.

    PubMed

    Connell, Sarah S; Balkany, Thomas J

    2006-08-01

    Cochlear implants are cost-effective auditory prostheses that safely provide a high-quality sensation of hearing to adults who are severely or profoundly deaf. In the past 5 years, progress has been made in hardware and software design, candidate selection, surgical techniques, device programming, education and rehabilitation,and, most importantly, outcomes. Cochlear implantation in the elderly is well tolerated and provides marked improvement in auditory performance and psychosocial functioning.

  14. Contraceptive implants.

    PubMed

    McDonald-Mosley, Raegan; Burke, Anne E

    2010-03-01

    Implantable contraception has been extensively used worldwide. Implants are one of the most effective and reversible methods of contraception available. These devices may be particularly appropriate for certain populations of women, including women who cannot use estrogen-containing contraception. Implants are safe for use by women with many chronic medical problems. The newest implant, Implanon (Organon International, Oss, The Netherlands), is the only device currently available in the United States and was approved in 2006. It is registered for 3 years of pregnancy prevention. Contraceptive implants have failure rates similar to tubal ligation, and yet they are readily reversible with a return to fertility within days of removal. Moreover, these contraceptive devices can be safely placed in the immediate postpartum period, ensuring good contraceptive coverage for women who may be at risk for an unintended pregnancy. Irregular bleeding is a common side effect for all progestin-only contraceptive implants. Preinsertion counseling should address possible side effects, and treatment may be offered to women who experience prolonged or frequent bleeding.

  15. An Improved Tumour Temperature Measurement and Control Method for Superficial Tumour Ultrasound Hyperthermia Therapeutic System

    NASA Astrophysics Data System (ADS)

    Shen1, G. F.; Chen, Y. Z.; Ren, G. X.

    2006-10-01

    In tumour hyperthermia therapy, the research on measurement and control of tumour temperature is very important. Based on the hardware platform of superficial tumour ultrasound hyperthermia therapeutic system, an improved tumour temperature measurement and control method is presented in this paper. The experiment process, data and results are discussed in detail. The improved method will greatly reduce the pain and dread of the patients during the therapy period on the tumour temperature measurement and control by using the pinhead sensor.

  16. 'Primary extrarenal Wilms' tumour': rare presentation of a common paediatric tumour.

    PubMed

    Goel, Vandana; Verma, Amit Kumar; Batra, Vineeta; Puri, Sunil Kumar

    2014-06-06

    Wilms' tumour (nephroblastoma), the most common abdominal malignancy of childhood, occurs primarily as a malignant renal tumour. Extrarenal Wilms' tumour is rare with occasional reports from the Indian subcontinent. The various locations of extrarenal Wilms' tumour include retroperitoneum, uterus, skin and thorax. In this report we will discuss the imaging features highlighting the imaging differential diagnosis in a case of retroperitoneal (extrarenal) primary Wilms' tumour.

  17. 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.

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

    PubMed

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

    2015-03-01

    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. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  19. Immunomodulatory and antitumour effects of abnormal Savda Munziq on S180 tumour-bearing mice

    PubMed Central

    2012-01-01

    Background Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. This study attempts to confirm these effects in vivo and measure effects on the immune system. Methods Kunming mice transplanted with Sarcoma 180 cells were treated with ASMq (2–8 g/kg/day) by intra-gastric administration compared to model and cyclophosphamide (20 mg/kg/day). After the 14th day post tumour implant, thymus, liver, spleen and tumours were removed, weighed, and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses including TNF-α , IL-1 β and IL-2. Splenic lymphocyte function was measured with MTT; lymphocyte subpopulations were measured by flow cytometry. Results ASMq treated animals had reduced tumour volume compared to model and increased concentrations of TNF-α, IL-1β and IL-2 compared to untreated and to cyclophosphamide-treated animals. No histopathological alterations were observed. The absence of viable S180 cells and the presence of necrotic cells and granulation tissue were observed in tumour tissue of treated animals. The effect on T lymphocytes was unclear. Conclusions ASMq confirmed in vivo anti-tumour effects observed in vitro, which may be at least in part mediated by increased immune activity. PMID:22978453

  20. A Pilot Study Investigating the Potential of High-Intensity Focused Ultrasound to Treat Tumours Rapidly

    NASA Astrophysics Data System (ADS)

    Cranston, Jonathan M.; Rivens, Ian; ter Haar, Gail; Kennedy, James

    2007-05-01

    The aim of this project was to investigate the possibility of rapid tumour destruction by a novel method of treating the periphery of a tumour and inducing ischemia by impeding the blood supply. Ex vivo experiments were initially carried out in bovine liver to determine the optimum conditions for focal depth, gantry transducer speed circle diameter and intensity of the ultrasound beam. In vivo experiments were then performed in PGV rat livers implanted with a HSN fibrosarcoma cell line. The tumours were treated by novel technique of creating an annular lesion around the perimeter of the tumour. Macroscopic and microscopic examination of the lesion at post mortem was performed. In addition histological examination of the untreated tumour which was within the annular circle of treatment was examined. This showed evidence of karyolytic nuclei a week after treatment suggesting death by infarction within this area. There was also some evidence of endothelial damage in the blood vessels with fragmented nuclei visible in the lumen. The work presented here adds to our understanding of how high intensity focused ultrasound may be used to treat tumours in as faster and more efficient way. Further work in this area will facilitate the design of future therapeutic interventions in the medical and veterinary world.

  1. 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

  2. Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice.

    PubMed

    Campbell, Elizabeth J; Vissers, Margreet C M; Wohlrab, Christina; Hicks, Kevin O; Strother, R Matthew; Bozonet, Stephanie M; Robinson, Bridget A; Dachs, Gabi U

    2016-10-01

    Despite recent evidence for an anti-tumour role for high-dose ascorbate, potential mechanisms of action are still unclear. At mM concentrations that are achieved with high-dose intravenous administration, autoxidation of ascorbate can generate cytotoxic levels of H2O2. Ascorbate is also a required co-factor for the hydroxylases that suppress the transcription factor hypoxia-inducible factor (HIF-1). HIF-1 supports an aggressive tumour phenotype and is associated with poor prognosis, and previous studies have shown that optimizing intracellular ascorbate levels down-regulates HIF-1 activation. In this study we have simultaneously measured ascorbate concentrations and the HIF-1 pathway activity in tumour tissue following high dose ascorbate administration, and have studied tumour growth and physiology. Gulo(-/-) mice, a model of the human ascorbate dependency condition, were implanted with syngeneic Lewis lung tumours, 1g/kg ascorbate was administered into the peritoneum, and ascorbate concentrations were monitored in plasma, liver and tumours. Ascorbate levels peaked within 30min, and although plasma and liver ascorbate returned to baseline within 16h, tumour levels remained elevated for 48h, possibly reflecting increased stability in the hypoxic tumour environment. The expression of HIF-1 and its target proteins was down-regulated with tumour ascorbate uptake. Elevated tumour ascorbate levels could be maintained with daily administration, and HIF-1 and vascular endothelial growth factor protein levels were reduced in these conditions. Increased tumour ascorbate was associated with slowed tumour growth, reduced tumour microvessel density and decreased hypoxia. Alternate day administration of ascorbate resulted in lower tumour levels and did not consistently decrease HIF-1 pathway activity. Levels of sodium-dependent vitamin C transporters 1 and 2 were not clearly associated with ascorbate accumulation by murine tumour cells in vitro or in vivo. Our results support

  3. Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth

    PubMed Central

    Shi, Yu; Ping, Yi-Fang; Zhou, Wenchao; He, Zhi-Cheng; Chen, Cong; Bian, Bai-Shi-Jiao; Zhang, Lin; Chen, Lu; Lan, Xun; Zhang, Xian-Chao; Zhou, Kai; Liu, Qing; Long, Hua; Fu, Ti-Wei; Zhang, Xiao-Ning; Cao, Mian-Fu; Huang, Zhi; Fang, Xiaoguang; Wang, Xiuxing; Feng, Hua; Yao, Xiao-Hong; Yu, Shi-Cang; Cui, You-Hong; Zhang, Xia; Rich, Jeremy N; Bao, Shideng; Bian, Xiu-Wu

    2017-01-01

    Intense infiltration of tumour-associated macrophages (TAMs) facilitates malignant growth of glioblastoma (GBM), but the underlying mechanisms remain undefined. Herein, we report that TAMs secrete abundant pleiotrophin (PTN) to stimulate glioma stem cells (GSCs) through its receptor PTPRZ1 thus promoting GBM malignant growth through PTN–PTPRZ1 paracrine signalling. PTN expression correlates with infiltration of CD11b+/CD163+ TAMs and poor prognosis of GBM patients. Co-implantation of M2-like macrophages (MLCs) promoted GSC-driven tumour growth, but silencing PTN expression in MLCs mitigated their pro-tumorigenic activity. The PTN receptor PTPRZ1 is preferentially expressed in GSCs and also predicts GBM poor prognosis. Disrupting PTPRZ1 abrogated GSC maintenance and tumorigenic potential. Moreover, blocking the PTN–PTPRZ1 signalling by shRNA or anti-PTPRZ1 antibody potently suppressed GBM tumour growth and prolonged animal survival. Our study uncovered a critical molecular crosstalk between TAMs and GSCs through the PTN–PTPRZ1 paracrine signalling to support GBM malignant growth, indicating that targeting this signalling axis may have therapeutic potential. PMID:28569747

  4. Isolation of inflammatory cells from human tumours.

    PubMed

    Polak, Marta E

    2011-01-01

    Inflammatory cells are present in many tumours, and understanding their function is of increasing importance, particularly to studies of tumour immunology. The tumour-infiltrating leukocytes encompass a variety of cell types, e.g. T lymphocytes, macrophages, dendritic cells, NK cells, and mast cells. Choice of the isolation method greatly depends on the tumour type and the leukocyte subset of interest, but the protocol usually includes tissue disaggregation and cell enrichment. We recommend density centrifugation for initial enrichment, followed by specific magnetic bead negative or positive panning with leukocyte and tumour cell selective antibodies.

  5. Malignant tumours of childhood in Zaria.

    PubMed

    Samaila, Modupeola Omotara

    2009-01-01

    The increased prevalence of hitherto uncommon tumours in children in our geographic setting formed the basis for this study. This study aimed to determine the current histopathologic distribution pattern of paediatric malignancies in Zaria. An eight year (2000-2007) consecutive analysis of malignant tumours in children ages 0 to 15 years in a referral University laboratory. All tissue biopsies were fixed in 10% formalin and processed in wax. Tumours were characterised histologically into tissues of origin and categorised into three age groups; <1 year, 1-5 years and 6-15 years. 189 children with malignant tumours were analysed. They showed a male preponderance (M: F; 1.2: 1.0) and their ages ranged from 5 days to 15 years. Tumours of mesenchymal origin were the commonest (115: 60.8%) while epithelial tumours including germ cell tumours accounted for 74 (39.2%) cases. The age group 1-5 years had the highest epithelial tumours while age group 6-15 years had the most tumours with 102 (54%) cases overall. The five commonest tumours over-all were rhabdomyosarcoma, Burkitt lymphoma, retinoblastoma, non-Hodgkin's lymphoma and nephroblastoma. Germ cell tumours affected the ovary predominantly and two of the endodermal sinus tumour cases were seen in the testis of an eighteen month child and sacrococcygeum of a 5 year old girl, respectively. Of the six immature teratoma cases, four were cutaneous in distribution. The vascular tumours included epithelioid haemangioendothelioma, haemangioblastoma and Dabska tumour and they accounted for (5.8%) of all tumours seen. The commonest sites of occurrence of these tumours were the oculo-orbital, jaw, head and neck regions with 82 cases (43.4%) while lymph nodes were involved in 31 (16.4%) cases. The distribution and occurrence of malignant tumours in children is age related. Lymphomas were the commonest tumours overall while retinoblastoma and Burkitt lymphoma were the commonest tumours affecting children below 5 years and 6-10 years

  6. Borderline ovarian tumours: clinical analysis of 38 cases.

    PubMed

    Behtash, N; Modares, M; Abolhasani, M; Ghaemmaghami, F; Mousavi, M; Yarandi, F; Hanjani, P

    2004-02-01

    Thirty-eight patients with ovarian tumours of low malignant potential (borderline) were diagnosed and treated in Tehran University Gynecology Oncology Department from 1991 to 2002, and have been reviewed. In this study age, clinical behavior, symptoms, surgical stage, type of tumour, surgery, adjuvant treatment, survival and recurrences were evaluated. A retrospective chart review was performed on these 38 patients who were treated for histopathologically confirmed tumours of low malignant potential between 1991-2002. The mean age was 34.4 years, range (14-83) (SD: 18.33). Post surgical FIGO staging was: Stage I=93.75%, stage III 6.25%. Histologic subtypes were: Serous 76.31% (29 patients), Mucinous 21.05% (8 patients), Mixed types 2.63% (1 patient). Mean pre-operative CA125 value was 114.90 (SD: +/- 90.30). Thirty-three percent of patients had only a simple cyst in ultrasonography. Conservative surgery was performed in 76.32% (29 patients). More radical surgery (TAH + BSO) was performed in 9 patients (23.68%). There were 6 recurrences. Three patients with recurrence and invasive implants received chemotherapy and secondary surgery was performed. Survival rate was 100% at 3 years for all stages and 89% at 5 years. One patient died of recurrent disease at 48 months after initial diagnosis. Our data suggest that LMP tumours are most frequently diagnosed in stage I. Most common histological type was serous, and 5 of the recurrences of (6 patients) were initially diagnosed at stage I, and had been treated with conservative surgery with no adjuvant therapy.

  7. Mechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure.

    PubMed

    Fernández-Sánchez, María Elena; Barbier, Sandrine; Whitehead, Joanne; Béalle, Gaëlle; Michel, Aude; Latorre-Ossa, Heldmuth; Rey, Colette; Fouassier, Laura; Claperon, Audrey; Brullé, Laura; Girard, Elodie; Servant, Nicolas; Rio-Frio, Thomas; Marie, Hélène; Lesieur, Sylviane; Housset, Chantal; Gennisson, Jean-Luc; Tanter, Mickaël; Ménager, Christine; Fre, Silvia; Robine, Sylvie; Farge, Emmanuel

    2015-07-02

    The tumour microenvironment may contribute to tumorigenesis owing to mechanical forces such as fibrotic stiffness or mechanical pressure caused by the expansion of hyper-proliferative cells. Here we explore the contribution of the mechanical pressure exerted by tumour growth onto non-tumorous adjacent epithelium. In the early stage of mouse colon tumour development in the Notch(+)Apc(+/1638N) mouse model, we observed mechanistic pressure stress in the non-tumorous epithelial cells caused by hyper-proliferative adjacent crypts overexpressing active Notch, which is associated with increased Ret and β-catenin signalling. We thus developed a method that allows the delivery of a defined mechanical pressure in vivo, by subcutaneously inserting a magnet close to the mouse colon. The implanted magnet generated a magnetic force on ultra-magnetic liposomes, stabilized in the mesenchymal cells of the connective tissue surrounding colonic crypts after intravenous injection. The magnetically induced pressure quantitatively mimicked the endogenous early tumour growth stress in the order of 1,200 Pa, without affecting tissue stiffness, as monitored by ultrasound strain imaging and shear wave elastography. The exertion of pressure mimicking that of tumour growth led to rapid Ret activation and downstream phosphorylation of β-catenin on Tyr654, imparing its interaction with the E-cadherin in adherens junctions, and which was followed by β-catenin nuclear translocation after 15 days. As a consequence, increased expression of β-catenin-target genes was observed at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci. Mechanical activation of the tumorigenic β-catenin pathway suggests unexplored modes of tumour propagation based on mechanical signalling pathways in healthy epithelial cells surrounding the tumour, which may contribute to tumour heterogeneity.

  8. 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

  9. Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities.

    PubMed

    Lin, L Y; Du, L M; Cao, K; Huang, Y; Yu, P F; Zhang, L Y; Li, F Y; Wang, Y; Shi, Y F

    2016-11-17

    Mesenchymal stromal cells (MSCs) are a major component of the tumour microenvironment. A plethora of elegant studies focusing on tumour-derived MSCs have shown that they, unlike normal MSCs in other tissue, exhibit a strong ability to promote tumour progression. However, the mechanisms underlying the conversion of normal MSCs into tumour-associated MSCs are unknown. We report here a critical role of tumour cell-derived exosomes in endowing bone marrow-derived MSCs (BM-MSCs) with a tumour-favourable phenotype. Tumour cell-derived exosomes affected neither the growth factor production nor the immunosuppressive property of MSCs; rather, they endowed MSCs with a strong ability to promote macrophage infiltration into B16-F0 melanoma or EL-4 lymphoma. Ablation of macrophages by clodronate liposome administration reversed the tumour-promoting effect of MSCs educated by tumour cell-derived exosomes (TE-MSCs) on the tumour growth. By comparing the chemokine profile of BM-MSCs with that of TE-MSCs, we found that TE-MSCs produced a large amount of CCR2 ligands, CCL2 and CCL7, which are responsible for macrophage recruitment. CCR2-specific inhibitor was found to block the tumour-promoting effect of TE-MSCs. Thus, our investigations demonstrated that tumour cell-derived exosomes confer BM-MSCs the ability to enhance tumour growth. Therefore, we uncovered a novel mechanism underlying the conversion of normal MSCs to tumour-associated MSCs.

  10. Notch as a tumour suppressor.

    PubMed

    Nowell, Craig S; Radtke, Freddy

    2017-03-01

    The Notch signalling cascade is an evolutionarily conserved pathway that has a crucial role in regulating development and homeostasis in various tissues. The cellular processes and events that it controls are diverse, and continued investigation over recent decades has revealed how the role of Notch signalling is multifaceted and highly context dependent. Consistent with the far-reaching impact that Notch has on development and homeostasis, aberrant activity of the pathway is also linked to the initiation and progression of several malignancies, and Notch can in fact be either oncogenic or tumour suppressive depending on the tissue and cellular context. The Notch pathway therefore represents an important target for therapeutic agents designed to treat many types of cancer. In this Review, we focus on the latest developments relating specifically to the tumour-suppressor activity of Notch signalling and discuss the potential mechanisms by which Notch can inhibit carcinogenesis in various tissues. Potential therapeutic strategies aimed at restoring or augmenting Notch-mediated tumour suppression will also be highlighted.

  11. Melanotic neuroectodermal tumour of infancy.

    PubMed

    Pattanayak Mohanty, Sweta; Ray, Jay Gopal; Richa; Mukherjee, Sanjit; Mandal, Chitra; Chaudhuri, Keya

    2010-11-23

    Melanotic neuroectodermal tumour of infancy (MNTI) is a rare benign tumour of neural crest origin that was first described by Krompecher in 1918.1 It is predominantly found in infancy, with about 92% of cases below the age of 12 months and 82% below the age of 6 months. The predominant site of origin is in the premaxilla though it is reported at other sites also including the skull, the mandible, the epididymis and the brain.2 The lesions often have areas of bluish discolouration on the surface and are characterised by displacement of the involved tooth bud and local aggressiveness. The present report deals with two cases of MNTI, a 5-month-old baby girl and a 6-month-old baby boy who reported to the Department of Oral and Maxillofacial Pathology, Dr R Ahmed Dental College and Hospital, Kolkata, India. The clinical, radiological, histological and immunohistochemical findings, confirmed the diagnosis of MNTI. Flow cytometry was performed to analyse aneuploidy. The tumours were treated surgically with no history of recurrence to date.

  12. Melanotic neuroectodermal tumour of infancy

    PubMed Central

    Pattanayak, Sweta; Ray, Jay Gopal; Richa; Mukherjee, Sanjit; Mandal, Chitra; Chaudhuri, Keya

    2010-01-01

    Melanotic neuroectodermal tumour of infancy (MNTI) is a rare benign tumour of neural crest origin that was first described by Krompecher in 1918.1 It is predominantly found in infancy, with about 92% of cases below the age of 12 months and 82% below the age of 6 months. The predominant site of origin is in the premaxilla though it is reported at other sites also including the skull, the mandible, the epididymis and the brain.2 The lesions often have areas of bluish discolouration on the surface and are characterised by displacement of the involved tooth bud and local aggressiveness. The present report deals with two cases of MNTI, a 5-month-old baby girl and a 6-month-old baby boy who reported to the Department of Oral and Maxillofacial Pathology, Dr R Ahmed Dental College and Hospital, Kolkata, India. The clinical, radiological, histological and immunohistochemical findings, confirmed the diagnosis of MNTI. Flow cytometry was performed to analyse aneuploidy. The tumours were treated surgically with no history of recurrence to date. PMID:22797196

  13. Latest advances in pancreatic tumours.

    PubMed

    Lariño Noia, José

    2016-09-01

    Pancreatic cancer continues to have a bleak prognosis. Hardly any therapeutic advances have been made in the last few years and consequently most efforts have focused on preventing its development and on diagnosing precursor lesions. In this regard, the use of statins as a preventive factor and the implementation of screening programmes in high-risk patients are gaining ground. In the field of treatment, there is greater focus on the role of neoadjuvant therapy in pancreatic cancer and on a multimodal approach to the disease, with few advances in effective novel therapies. Most studies concerned cystic tumours of the pancreas, especially intraductal mucinous papillary tumour, with its known potential for malignant transformation. Multiple studies were devoted to validation of the 2012 Fukuoka international guidelines and the highly controversial 2015 AGA guidelines. Notable among these studies were those demonstrating the suboptimal positive predictive value and questioning important aspects of the guidelines, such as discontinuation of follow-up or the criteria for surgical referral. Notable among diagnostic procedures were cystoscopy and endoscopic ultrasound-guided needle-based confocal laser endomicroscopy as the most promising techniques due to their high efficacy and negative predictive value in detecting mucinous cystic lesions. There were also a large number of studies on the natural history of intraductal papillary mucinous tumours, which help deepen knowledge of these entities and the search for predictive factors of cancer development. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. New frontiers for astrocytic tumours.

    PubMed

    Nano, Rosanna; Lascialfari, Alessandro; Corti, Maurizio; Paolini, Alessandro; Pasi, Francesca; Corbella, Franco; DI Liberto, Riccardo

    2012-07-01

    Glioblastoma multiforme, the most common type of primary brain tumour, remains an unsolved clinical problem. A great deal of work has been done in an effort to understand the biology and genetics of glioblastoma multiforme, but clinically effective treatments remain elusive. It is well known that malignant gliomas develop resistance to chemo- and radiotherapy. In this review we evaluated the literature data regarding therapeutic progress for the treatment of astrocytic tumours, focusing our attention on new frontiers for glioblastoma. The research studies performed in in vitro and in vivo models show that the application of hyperthermia using magnetic nanoparticles is safe and could be a promising tool in the treatment of glioblastoma patients. Our efforts are focused towards new fields of research, for example nanomedicine and the study of the uptake and cytotoxic effects of magnetic nanoparticles. The improvement of the quality of life of patients, by increasing their survival rate is the best result to be pursued, since these tumours are considered as ineradicable.

  15. Mathematical models of tumour angiogenesis

    NASA Astrophysics Data System (ADS)

    Kubo, Akisato; Suzuki, Takashi

    2007-07-01

    We first study a parabolic-ODE system modelling tumour growth proposed by Othmer and Stevens [Aggregation, blowup, and collapse: the ABC's of taxis in reinforced random walks, SIAM J. Appl. Math. 57 (4) (1997) 1044-1081]. According to Levine and Sleeman [A system of reaction and diffusion equations arising in the theory of reinforced random walks, SIAM J. Appl. Math. 57 (3) (1997) 683-730], we reduced it to a hyperbolic equation and showed the existence of collapse in [A. Kubo, T. Suzuki, Asymptotic behavior of the solution to a parabolic ODE system modeling tumour growth, Differential Integral Equations 17 (2004) 721-736]. We also deal with the system in case the reduced equation is elliptic and show the existence of collapse analogously. Next we apply the above result to another model proposed by Anderson and Chaplain arising from tumour angiogenesis and show the existence of collapse. Further we investigate a contact point between these two models and a common property to them.

  16. Establishing a rabbit model of malignant esophagostenosis using the endoscopic implantation technique for studies on stent innovation

    PubMed Central

    2014-01-01

    Background Stents are recommended in patients with dysphagia caused by esophageal stricture, but an ideal stent does not currently exist. Thus, studies on new esophageal stents are necessary, and suitable animal models are desperately needed for these studies. The aim of this study was to establish a model of malignant esophageal stricture in rabbit for studies on stent innovation. Methods A total of 38 New Zealand white rabbits were used in this study. Using the endoscopic submucosal injection technique, VX2 fragments were inoculated into the submucosal layer of the rabbit thoracic esophagus, and an endoscopic follow-up was subsequently performed to observe the tumor development and progression. The self-expandable metal stents were randomly deployed in rabbits with severe esophageal stricture to investigate the safety and feasibility of the animal models for stenting. Results An endoscopic implantation procedure for VX2 tumors was completed in 34/38 rabbits, and tumor development was confirmed in 30/34 animals. The success rate of the endoscopic implantation and tumor development were 89.4% (95% CI, 79.6% to 99.2%) and 88.2% (95% CI, 76.9% to 99.5%) respectively. During the endoscopic follow-up period, severe esophageal stricture occurred in 22/30 rabbits with a rate of 73.3% (95% CI, 57.5% to 89.1%), and 12/22 models received stent placement. During and after stent implantation, no severe stent-related complication or mortality occurred in the animal models. The rabbits that received stent placement survived longer than those without stent implantation (the mean survival time: 53.9 days versus 40.3 days, P = 0.016). Conclusion The endoscopic method is a safe and effective method for establishing a malignant esophagostenosis model in rabbits. This model can simulate the human body environment for stent deployment and is an excellent tool for the study of stent innovation for the treatment of esophageal cancer. PMID:24507720

  17. PET imaging of primary mediastinal tumours.

    PubMed Central

    Kubota, K.; Yamada, S.; Kondo, T.; Yamada, K.; Fukuda, H.; Fujiwara, T.; Ito, M.; Ido, T.

    1996-01-01

    Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tumours were studied with PET using 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The histological findings of surgical pathology or biopsy, or mediastinoscopy were compared with those of computerised tomography (CT) and PET. PET images were evaluated semiquantitatively using the differential uptake ratio (DUR). Increased FDG uptake was observed in nine of ten patients with malignant tumours, including thymic carcinomas, lymphomas, invasive thymomas and a case of sarcoidosis. A moderate level of FDG uptake was found in a myeloma, non-invasive thymomas, and a schwannoma, whereas a low uptake was observed in a teratoma and various benign cysts. The mean FDG uptake of malignant tumours was significantly higher than that of benign tumours. Both thymic cancer and invasive thymoma showed a high FDG uptake. CT examination resulted in three false-negative and two false-positive cases when used in predicting tumour invasion, while PET was associated with a false-positive and a false-negative case. In conclusion, the use of FDG with PET is clinically helpful in evaluating the malignant nature of primary mediastinal tumours. Our results also suggest that a high FDG uptake reflects the invasiveness of malignant nature of thymic tumours. Images Figure 1 Figure 2 PMID:8611400

  18. DNA methyltransferase immunohistochemical expression in odontogenic tumours.

    PubMed

    Guimarães, Douglas Magno; Antunes, Daniella Moraes; Duarte, Carina Magalhães Esteves; Ferro, Leonardo Borges; Nunes, Fabio Daumas

    2015-01-01

    Odontogenic tumours are a heterogeneous group of lesions formed from tissues that give rise to the tooth. DNA methylation, a covalent addition of a methyl group to the 5-carbon position of a cytosine nucleotide, is considered an important regulator of gene expression. The addition of the methyl radical is catalysed by DNA methyltransferases (DNMTs). Although some epigenetic studies have been conducted in odontogenic tumours, a study with the three types of DNMTs in several different members of this group is missing. This study analyses the expression of DNMTs in odontogenic tumours. Formalin-fixed and paraffin-embedded tissue samples of 20 ameloblastomas, 10 calcifying cystic odontogenic tumours, 10 calcifying epithelial tumours, 10 adenomatoid odontogenic tumours, 10 keratocystic odontogenic tumours, five ameloblastic fibromas, two ameloblastic fibro-odontomas, four central odontogenic fibromas, seven peripheral odontogenic fibromas and 10 odontogenic myxomas were included. Immunohistochemical expression of DNMT1, 3A and 3B was assessed using a semi-quantitative analysis, and also a correlation with p21, p27 and E-cadherin immunoexpression was made. DNMT1, 3A and 3B were expressed in the nucleus and/or cytoplasm of all odontogenic tumours. DNMT1 expression was directly correlated with p27 expression in ameloblastomas. The high expression of DNMTs in odontogenic tumour cells suggests methylation as an important mechanism for this group of tumours. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Gene expression profiling of human ovarian tumours

    PubMed Central

    Biade, S; Marinucci, M; Schick, J; Roberts, D; Workman, G; Sage, E H; O'Dwyer, P J; LiVolsi, V A; Johnson, S W

    2006-01-01

    There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT–PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers. PMID:16969345

  20. Gene expression profiling of human ovarian tumours.

    PubMed

    Biade, S; Marinucci, M; Schick, J; Roberts, D; Workman, G; Sage, E H; O'Dwyer, P J; Livolsi, V A; Johnson, S W

    2006-10-23

    There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT-PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers.

  1. Tumour location within the breast: Does tumour site have prognostic ability?

    PubMed

    Rummel, Seth; Hueman, Matthew T; Costantino, Nick; Shriver, Craig D; Ellsworth, Rachel E

    2015-01-01

    Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. All patients enrolled in the Clinical Breast Care Project whose tumour site-UOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)-was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P < 0.05. Of the 980 patients with defined tumour location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P < 0.001), metastatic lymph nodes (P < 0.001), and mortality (P = 0.011). After multivariate analysis, only tumour size and lymph node status remained significantly associated with survival. Evaluation of tumour location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor.

  2. Role of Delta-like 4 in Jagged1-induced tumour angiogenesis and tumour growth

    PubMed Central

    Oon, Chern Ein; Bridges, Esther; Sheldon, Helen; Sainson, Richard C.A.; Jubb, Adrian; Turley, Helen; Leek, Russell; Buffa, Francesca; Harris, Adrian L.; Li, Ji-Liang

    2017-01-01

    Delta-like 4 (DLL4) and Jagged1 (JAG1) are two key Notch ligands implicated in tumour angiogenesis. They were shown to have opposite effects on mouse retinal and adult regenerative angiogenesis. In tumours, both ligands are upregulated but their relative effects and interactions in tumour biology, particularly in tumour response to therapeutic intervention are unclear. Here we demonstrate that DLL4 and JAG1 displayed equal potency in stimulating Notch target genes in HMEC-1 endothelial cells but had opposing effects on sprouting angiogenesis in vitro. Mouse DLL4 or JAG1 expressed in glioblastoma cells decreased tumour cell proliferation in vitro but promoted tumour growth in vivo. mDLL4-expressing tumours showed fewer but larger vessels whereas mJAG1-tumours produced more vessels. In both tumour types pericyte coverage was decreased but the vessels were more perfused. Both ligands increased tumour resistance towards anti-VEGF therapy but the resistance was higher in mDLL4-tumours versus mJAG1-tumours. However, their sensitivity to the therapy was restored by blocking Notch signalling with dibenzazepine. Importantly, anti-DLL4 antibody blocked the effect of JAG1 on tumour growth and increased vessel branching in vivo. The mechanism behind the differential responsiveness was due to a positive feedback loop for DLL4-Notch signalling, rendering DLL4 more dominant in activating Notch signalling in the tumour microenvironment. We concluded that DLL4 and JAG1 promote tumour growth by modulating tumour angiogenesis via different mechanisms. JAG1 is not antagonistic but utilises DLL4 in tumour angiogenesis. The results suggest that anti-JAG1 therapy should be explored in conjunction with anti-DLL4 treatment in developing anti-Notch therapies in clinics. PMID:28445154

  3. 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

  4. 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

  5. Bioluminescent Orthotopic Mouse Models of Human Localized Non-Small Cell Lung Cancer: Feasibility and Identification of Circulating Tumour Cells

    PubMed Central

    Lahon, Benoit; Castier, Yves; Lesèche, Guy; Soria, Jean-Charles; Vozenin, Marie-Catherine; Decraene, Charles; Deutsch, Eric

    2011-01-01

    Background Preclinical models of non-small cell lung cancer (NSCLC) require better clinical relevance to study disease mechanisms and innovative therapeutics. We sought to compare and refine bioluminescent orthotopic mouse models of human localized NSCLC. Methods Athymic nude mice underwent subcutaneous injection (group 1-SC, n = 15, control), percutaneous orthotopic injection (group 2-POI, n = 30), surgical orthotopic implantation of subcutaneously grown tumours (group 3-SOI, n = 25), or transpleural orthotopic injection (group 4-TOI, n = 30) of A549-luciferase cells. Bioluminescent in vivo imaging was then performed weekly. Circulating tumour cells (CTCs) were searched using Cellsearch® system in SC and TOI models. Results Group 2-POI was associated with unexpected direct pleural spreading of the cellular solution in 53% of the cases, forbidding further evaluation of any localized lung tumour. Group 3-SOI was characterized by high perioperative mortality, initially localized lung tumours, and local evolution. Group 4-TOI was associated with low perioperative mortality, initially localized lung tumours, loco regional extension, and distant metastasis. CTCs were detected in 83% of nude mice bearing subcutaneous or orthotopic NSCLC tumours. Conclusions Transpleural orthotopic injection of A549-luc cells in nude mouse lung induces localized tumour, followed by lymphatic extension and specific mortality, and allowed the first time identification of CTCs in a NSCLC mice model. PMID:22022511

  6. [Solitary fibrous tumours of the kidney].

    PubMed

    Gres, Pascal; Avances, Christophe; Ben Naoum, Kamel; Chapuis, Héliette; Costa, Pierre

    2004-02-01

    Solitary fibrous tumours (SFT) are mesenchymal tumours that usually arise from the pleura. Renal SFT are exceptional (9 cases reported in the literature). The authors report a new case discovered during assessment of HT and treated by radical right nephrectomy. The histological appearance is characteristic: a tumour with a fibrous centre, composed of a monomorphic proliferation of spindle cells, with positive CD 34, CD 99, and bcl 2 labelling. The prognosis after complete resection is generally favourable.

  7. Surgical treatment of benign endobronchial tumours

    PubMed Central

    Halttunen, P; Meurala, H; Standertskjöld-Nordenstam, C-G

    1982-01-01

    Four cases of benign endobronchial tumour are reported which were successfully treated by bronchial resection. In two cases (of fibroma and leiomyoma respectively) a cylinder of bronchus alone was resected; in one case (lipoma) a healthy right upper lobe was preserved by a bronchoplastic procedure and in the other (chondroma) the tumour was removed with the right lower lobe, which was irreversibly damaged. It is important to recognise that such tumours are unsuitable for treatment by endoscopic means alone. Images PMID:7157223

  8. 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.

  9. Histogenesis of ovarian malignant mixed mesodermal tumours.

    PubMed Central

    Clarke, T J

    1990-01-01

    The histogenesis of ovarian malignant mixed mesodermal tumours, which includes the concept of metaplastic carcinoma, is controversial. Four such tumours were examined for evidence of metaplastic transition from carcinoma to sarcoma using morphology and reticulin stains. Consecutive sections were stained immunohistochemically using cytokeratin and vimentin to determine whether cells at the interface between carcinoma and sarcoma expressed both cytokeratin and vimentin. There was no evidence of morphological, architectural, or immunohistochemical transitions from carcinoma to sarcoma in the four tumours studied. This suggests that ovarian malignant mixed mesodermal tumours are not metaplastic carcinomas but are composed of histogenetically different elements. Images PMID:2160478

  10. Endovascular treatment of primary hepatic tumours

    PubMed Central

    Popiel, M; Gulie, L; Turculeţ, C; Beuran, M

    2008-01-01

    First transcatheter embolization of hepatic artery has been materializing in 1974, in France, for unresectable hepatic tumours. Then, this treatment has become use enough in many countries, especially in Japan, where primary hepatic tumours are very frequent. In this article, we present procedures of interventional endovascular treatment for primary hepatic tumours: chemoembolization, intra–arterial chemotherapy. The study comprises patients with primary hepatic tumours investigated by hepatic–ultrasound and contrast–enhanced CT or MRI. DSA–hepatic angiography is very important to verify the accessory hepatic supply. It has been performed selective catheterization of right/left hepatic branches followed by cytostatics injection. Most of the patients have benefit by hepatic chemoembolization (cytostatics, Lipiodol and embolic materials). The selective intra–arterial chemotherapy (cytostatics without Lipiodol) was performing in cases with contraindications for Lipiodol or embolic materials injection (cirrhosis–Child C, thrombosis of portal vein, hepatic insufficiency). For treatment of primary hepatic tumours we use 5–F–Uracil, Farmarubicin and Mytomicin C. Less numbers of the reservoirs were placed because financial causes. Chemoembolization was better than procedures without Lipiodol or embolic materials. Lipiodol reached in tumoural tissue and the distribution of Lipiodol harmonises with degree of vascularisation. After the chemoembolization procedure, the diameter of tumours decreased gradually depending on the size of tumour. Effective alternative for unresectable primary hepatic tumours (big size, hepatic dysfunction, and other surgical risk factors) is endovascular interventional treatment. PMID:20108517

  11. 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

  12. Diagnostic utility of Wilms’ tumour-1 protein (WT-1) immunostaining in paediatric renal tumours

    PubMed Central

    Goyal, Surbhi; Mishra, Kiran; Sarkar, Urvee; Sharma, Satendra; Kumari, Anita

    2016-01-01

    Background & objectives: Renal tumours constitute about 7 per cent of all neoplasms in children. It is important to differentiate Wilms’ tumour (commonest tumour) from non-Wilms’ tumours. The aim of this study was to evaluate the immunoexpression and diagnostic role of Wilms’ tumour-1 protein (WT1) in paediatric renal tumours. Methods: A total of 53 cases of renal tumours in children (below 18 yr) who underwent total nephrectomy were included in this retrospective study. WT1 immunostaining was done using mouse monoclonal WT1 antibody (clone: 6F-H2). Results: Of the 53 cases, 38 (72%) were of Wilms’ tumour. Non-Wilms’ group (15) included six cases of mesoblastic nephroma (MN), two each of clear cell sarcoma (CCSK), renal cell carcinoma (RCC) and peripheral neuroectodermal tumour (PNET) and one each of angiomyolipoma (AML), rhabdomyosarcoma (RMS) and malignant rhabdoid tumour (MRT). Proportion of WT1 positivity in Wilms’ tumour was 100 per cent in contrast to 26.7 per cent in non-Wilms’ tumours (P<0.001). Epithelial and blastemal components of Wilms’ tumour showed moderate (2+) nuclear and cytoplasmic staining in 80 (24/30) and 75 per cent (24/32) cases, respectively. MN, PNET, CCSK and AML were negative for WT1. RMS, RCC and MRT showed cytoplasmic staining, strongest in RMS. No significant association was seen between WT1 expression and NWTSG (National Wilms’ Tumor Study Group) stage. Interpretation & conclusions: WT1 helps to differentiate Wilms’ tumour from other paediatric renal tumours. It may help in differentiating the two subgroups of Wilms’ tumour which have distinct molecular pathogenesis and biological behaviour, however, further prospective studies are required for validation of this hypothesis. PMID:27748279

  13. Prognostic impact of tumour size in completely resected thymic epithelial tumours.

    PubMed

    Fukui, Takayuki; Fukumoto, Koichi; Okasaka, Toshiki; Kawaguchi, Koji; Nakamura, Shota; Hakiri, Shuhei; Ozeki, Naoki; Hirakawa, Akihiro; Tateyama, Hisashi; Yokoi, Kohei

    2016-12-01

    The T descriptor of thymic epithelial tumours proposed by the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group as well as the Masaoka-Koga system is defined by the anatomical extent of primary tumours, regardless of their size. However, the prognostic significance of tumour size in thymic epithelial tumours has not been fully elucidated. We evaluated the prognostic significance of tumour size in 154 consecutive patients with thymic epithelial tumours including 124 thymomas, 21 thymic carcinomas and 9 neuroendocrine tumours, who underwent complete resection between 2001 and 2014. Among all tumours, the median tumour size was 4.9 cm. The median thymoma, thymic carcinoma and neuroendocrine tumour sizes were 4.8, 5.7 and 5.8, respectively, although the differences were not significant. In survival analysis, the 5- and 10-year overall survival (OS) and recurrence-free survival (RFS) rates for all patients were 91 and 81%, and 80 and 69%, respectively. Under the stratification of tumour size, no trend was observed for OS, whereas RFS showed stepwise deterioration as tumour size increased. For 119 patients with Stage I disease, RFS showed deterioration as tumour size increased. Multivariate analysis revealed that tumour size >4.0 cm was an independent prognostic factor for worsening RFS (P = 0.03). Patients with tumours >4.0 cm showed significantly worse outcomes in RFS compared with those with smaller tumours. This relationship was also noted in patients with Stage I disease. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  14. Diagnostic utility of Wilms' tumour-1 protein (WT-1) immunostaining in paediatric renal tumours.

    PubMed

    Goyal, Surbhi; Mishra, Kiran; Sarkar, Urvee; Sharma, Satendra; Kumari, Anita

    2016-05-01

    Renal tumours constitute about 7 per cent of all neoplasms in children. It is important to differentiate Wilms' tumour (commonest tumour) from non-Wilms' tumours. The aim of this study was to evaluate the immunoexpression and diagnostic role of Wilms' tumour-1 protein (WT1) in paediatric renal tumours. A total of 53 cases of renal tumours in children (below 18 yr) who underwent total nephrectomy were included in this retrospective study. WT1 immunostaining was done using mouse monoclonal WT1 antibody (clone: 6F-H2). Of the 53 cases, 38 (72%) were of Wilms' tumour. Non-Wilms' group (15) included six cases of mesoblastic nephroma (MN), two each of clear cell sarcoma (CCSK), renal cell carcinoma (RCC) and peripheral neuroectodermal tumour (PNET) and one each of angiomyolipoma (AML), rhabdomyosarcoma (RMS) and malignant rhabdoid tumour (MRT). Proportion of WT1 positivity in Wilms' tumour was 100 per cent in contrast to 26.7 per cent in non-Wilms' tumours ( P<0.001). Epithelial and blastemal components of Wilms' tumour showed moderate (2+) nuclear and cytoplasmic staining in 80 (24/30) and 75 per cent (24/32) cases, respectively. MN, PNET, CCSK and AML were negative for WT1. RMS, RCC and MRT showed cytoplasmic staining, strongest in RMS. No significant association was seen between WT1 expression and NWTSG (National Wilms' Tumor Study Group) stage. WT1 helps to differentiate Wilms' tumour from other paediatric renal tumours. It may help in differentiating the two subgroups of Wilms' tumour which have distinct molecular pathogenesis and biological behaviour, however, further prospective studies are required for validation of this hypothesis.

  15. Clinical course and outcome of pregnancies in amenorrhoeic women with hyperprolactinaemia and pituitary tumours

    PubMed Central

    Bergh, Torbjörn; Nillius, Sven Johan; Wide, Leif

    1978-01-01

    Seventeen term pregnancies occurred in 14 amenorrhoeic women with hyperprolactinaemia and radiological evidence of pituitary tumour. The abortion rate was high (32%). All but one of the term pregnancies occurred after ovulation-inducing treatment with human gonadotrophins and bromocriptine (four and 12 pregnancies respectively). Two of the 14 women had visual complications during pregnancy, but neither had serious residual visual impairment. Two patients had possible pituitary enlargement during pregnancy. Bromocriptine may be the most suitable primary treatment for many infertile women with prolactin-secreting tumours. Tumour complications during pregnancy are a definite risk, but most pregnancies went uneventfully to term. Patients with pituitary tumour should be carefully evaluated before starting ovulation-inducing treatment with bromocriptine alone, and they should be told of the possible risks and of the advantages and disadvantages of pretreatment with irradiation or surgery. Patients should be carefully monitored during pregnancy and have their visual fields checked frequently. If visual complications due to tumour enlargement occur during a pregnancy, reinstituting bromocriptine may be the treatment of choice. If this fails, other forms of treatment such as induction of labour, high-dose corticosteroid treatment, pituitary implantation of yttrium-90, or surgery may be effective. ImagesFIG 1FIG 2 PMID:638504

  16. Particle therapy of moving targets-the strategies for tumour motion monitoring and moving targets irradiation.

    PubMed

    Kubiak, Tomasz

    2016-10-01

    Particle therapy of moving targets is still a great challenge. The motion of organs situated in the thorax and abdomen strongly affects the precision of proton and carbon ion radiotherapy. The motion is responsible for not only the dislocation of the tumour but also the alterations in the internal density along the beam path, which influence the range of particle beams. Furthermore, in case of pencil beam scanning, there is an interference between the target movement and dynamic beam delivery. This review presents the strategies for tumour motion monitoring and moving target irradiation in the context of hadron therapy. Methods enabling the direct determination of tumour position (fluoroscopic imaging of implanted radio-opaque fiducial markers, electromagnetic detection of inserted transponders and ultrasonic tumour localization systems) are presented. Attention is also drawn to the techniques which use external surrogate motion for an indirect estimation of target displacement during irradiation. The role of respiratory-correlated CT [four-dimensional CT (4DCT)] in the determination of motion pattern prior to the particle treatment is also considered. An essential part of the article is the review of the main approaches to moving target irradiation in hadron therapy: gating, rescanning (repainting), gated rescanning and tumour tracking. The advantages, drawbacks and development trends of these methods are discussed. The new accelerators, called "cyclinacs", are presented, because their application to particle therapy will allow making a breakthrough in the 4D spot scanning treatment of moving organs.

  17. Particle therapy of moving targets—the strategies for tumour motion monitoring and moving targets irradiation

    PubMed Central

    2016-01-01

    Particle therapy of moving targets is still a great challenge. The motion of organs situated in the thorax and abdomen strongly affects the precision of proton and carbon ion radiotherapy. The motion is responsible for not only the dislocation of the tumour but also the alterations in the internal density along the beam path, which influence the range of particle beams. Furthermore, in case of pencil beam scanning, there is an interference between the target movement and dynamic beam delivery. This review presents the strategies for tumour motion monitoring and moving target irradiation in the context of hadron therapy. Methods enabling the direct determination of tumour position (fluoroscopic imaging of implanted radio-opaque fiducial markers, electromagnetic detection of inserted transponders and ultrasonic tumour localization systems) are presented. Attention is also drawn to the techniques which use external surrogate motion for an indirect estimation of target displacement during irradiation. The role of respiratory-correlated CT [four-dimensional CT (4DCT)] in the determination of motion pattern prior to the particle treatment is also considered. An essential part of the article is the review of the main approaches to moving target irradiation in hadron therapy: gating, rescanning (repainting), gated rescanning and tumour tracking. The advantages, drawbacks and development trends of these methods are discussed. The new accelerators, called “cyclinacs”, are presented, because their application to particle therapy will allow making a breakthrough in the 4D spot scanning treatment of moving organs. PMID:27376637

  18. Tumour-to-tumour metastases: prostate carcinoma metastasising to a renal oncocytoma.

    PubMed

    Petts, Gemma; Rashid, Tina; Hrouda, David; Ngo, Nye-Thane

    2013-01-09

    This is a case report of prostate carcinoma metastasising to a renal oncocytoma. The report demonstrates the unusual presentation of metastases from a common cancer to a common benign tumour, and reviews the rare phenomenon of tumour-to-tumour metastases.

  19. Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.

    PubMed

    Eyre, Rachel; Alférez, Denis G; Spence, Kath; Kamal, Mohamed; Shaw, Frances L; Simões, Bruno M; Santiago-Gómez, Angélica; Sarmiento-Castro, Aida; Bramley, Maria; Absar, Mohammed; Saad, Zahida; Chatterjee, Sumohan; Kirwan, Cliona; Gandhi, Ashu; Armstrong, Anne C; Wardley, Andrew M; O'Brien, Ciara S; Farnie, Gillian; Howell, Sacha J; Clarke, Robert B

    2016-12-01

    Breast cancer specific mortality results from tumour cell dissemination and metastatic colonisation. Identification of the cells and processes responsible for metastasis will enable better prevention and control of metastatic disease, thus reducing relapse and mortality. To better understand these processes, we prospectively collected 307 patient-derived breast cancer samples (n = 195 early breast cancers (EBC) and n = 112 metastatic samples (MBC)). We assessed colony-forming activity in vitro by growing isolated cells in both primary (formation) and secondary (self-renewal) mammosphere culture, and tumour initiating activity in vivo through subcutaneous transplantation of fragments or cells into mice. Metastatic samples formed primary mammosphere colonies significantly more frequently than early breast cancers and had significantly higher primary mammosphere colony formation efficiency (0.9 % vs. 0.6 %; p < 0.0001). Tumour initiation in vivo was significantly higher in metastatic than early breast cancer samples (63 % vs. 38 %, p = 0.04). Of 144 breast cancer samples implanted in vivo, we established 20 stable patient-derived xenograft (PDX) models at passage 2 or greater. Lung metastases were detected in mice from 14 PDX models. Mammosphere colony formation in vitro significantly correlated with the ability of a tumour to metastasise to the lungs in vivo (p = 0.05), but not with subcutaneous tumour initiation. In summary, the breast cancer stem cell activities of colony formation and tumour initiation are increased in metastatic compared to early samples, and predict metastasis in vivo. These results suggest that breast stem cell activity will predict for poor outcome tumours, and therapy targeting this activity will improve outcomes for patients with metastatic disease.

  20. Gastrointestinal Stromal Tumours: An Update

    PubMed Central

    Somerhausen, Nicolas De Saint Aubain

    1998-01-01

    Purpose. To study the evolution of concepts concerning gastrointestinal stromal tumours (GISTs) over 30 years. Discussion. GISTs have been, for more than 30 years, the subject of considerable controversy regarding their line of differentiation as well as the prediction of their behaviour. Furthermore, once they spread within the peritoneal cavity, they are extremely hard to control. The recent findings of c-Kit mutations and the immunohistochemical detection of the product of this gene, KIT or CD117, in the mainly non-myogenic subset of this family of tumours, has led to a reappraisal of this group of lesions, which, with some exceptions, is now thought to be derived from the interstitial cells of Cajal, and this has facilitated a clearer definition of their pathological spectrum. In this article, we review chronologically the evolution of the concept of GIST with the gradual application of electron microscopy, immunohistochemistry, DNA ploidy analysis. We discuss the impact of these techniques on the pathological assessment and clinical management of GISTs. PMID:18521245

  1. 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.

  2. Intra-tumour heterogeneity - going beyond genetics.

    PubMed

    Caiado, Francisco; Silva-Santos, Bruno; Norell, Håkan

    2016-06-01

    Cancer patients die primarily due to disease recurrence after transient treatment responses. The emergence of therapy-resistant escape variants is fuelled by intra-tumour heterogeneity, underpinned by interference and Darwinian evolution among continuously developing sub-clones in the mutating tumour. Novel cancer cell variants build upon the pre-existing genetic landscape and tumour heterogeneity is often ascribed largely to genetic variability. While mutations are required for cancer development and studies of genetic evolution of tumours have improved our understanding of cancer biology, genetics only represents one dimension of the fitness of each cancer cell. Beyond the mutations, several non-genetic factors also add significant variability, resulting in a complex and highly dynamic tumour cell population that can drive disease under almost any condition. This viewpoint article summarizes the genetic basis of intra-tumour heterogeneity, before dissecting four major interdependent non-genetic factors we think critically contribute to the overall variability of tumour cells in all types of cancer: epigenetic regulation, cellular differentiation hierarchies, gene expression stochasticity and tumour microenvironment. We finally present the relevant technological approaches to address the combined contribution of both genetic and non-genetic factors to intra-tumour heterogeneity, focusing on genomic profiling, cellular lineage tracing and single-cell RNA sequencing technologies. This strategy will ultimately allow dissection of the full range and depth of intra-tumour heterogeneity. We thus believe that understanding how cancer genetics synergize with the emerging non-genetic factors will be key for development of therapies able to tackle tumour escape and thereby improve cancer patient survival. © 2016 Federation of European Biochemical Societies.

  3. CXCL10 alters the tumour immune microenvironment and disease progression in a syngeneic murine model of high-grade serous ovarian cancer.

    PubMed

    K Au, Katrina; Peterson, Nichole; Truesdell, Peter; Reid-Schachter, Gillian; Khalaj, Kasra; Ren, Runhan; Francis, Julie-Ann; Graham, Charles H; Craig, Andrew W; Koti, Madhuri

    2017-06-01

    We recently established that high STAT1 expression and associated T helper type I tumour immune microenvironment (TME) are prognostic and chemotherapy response predictive biomarkers in high-grade serous ovarian cancer (HGSC). STAT1 induced chemokine CXCL10 is key to the recruitment of lymphocytes in the TME and is significantly highly expressed in the tumours from patients with longer survival. In the current study we therefore aimed to elucidate the role CXCL10 in disease progression and tumour immune transcriptomic alterations using the ID8 syngeneic murine model of HGSC. ID8 ovarian cancer cells were engineered for stable knockdown (KD) and overexpression (OX) of CXCL10. The OX and KD cell line derivatives, along with their respective vector controls, were implanted in immunocompetent C57BL/6 mice via intra-peritoneal injections. At end point, immune transcriptomic profiling of tumour tissues and multiplex cytokine profiling of ascites, was performed. Effect of CXCL10 expression on the tumour vasculature and tumour cell proliferation was evaluated by CD31 and Ki67 immunostaining, respectively. Increased CXCL10 expression led to decreased tumour burden and malignant ascites accumulation in the ID8 syngeneic murine model of HGSC. The ascites levels of IL-6 and VEGF were significantly reduced in OX mice compared to the vector controls. The OX tumours also showed reduced vasculature (CD31) and proliferative index (Ki67) compared to the control tumours. Significantly higher expression of genes associated with antigen processing, apoptosis and T cell function was observed in OX tumours compared to the controls. Reduced CXCL10 expression in tumours from KD mice led to increased ascites accumulation and disease progression compared to the controls. CXCL10 is a positive determinant of anti-tumour immune responses in HGSC TME and disease progression. These findings are foundational for future translational studies aimed at improving treatment response and survival in HGSC

  4. Short Implants: New Horizon in Implant Dentistry

    PubMed Central

    Gulati, Manisha; Garg, Meenu; Pathak, Chetan

    2016-01-01

    The choice of implant length is an essential factor in deciding the survival rates of these implants and the overall success of the prosthesis. Placing an implant in the posterior part of the maxilla and mandible has always been very critical due to poor bone quality and quantity. Long implants can be placed in association with complex surgical procedures such as sinus lift and bone augmentation. These techniques are associated with higher cost, increased treatment time and greater morbidity. Hence, there is need for a less invasive treatment option in areas of poor bone quantity and quality. Data related to survival rates of short implants, their design and prosthetic considerations has been compiled and structured in this manuscript with emphasis on the indications, advantages of short implants and critical biomechanical factors to be taken into consideration when choosing to place them. Studies have shown that comparable success rates can be achieved with short implants as those with long implants by decreasing the lateral forces to the prosthesis, eliminating cantilevers, increasing implant surface area and improving implant to abutment connection. Short implants can be considered as an effective treatment alternative in resorbed ridges. Short implants can be considered as a viable treatment option in atrophic ridge cases in order to avoid complex surgical procedures required to place long implants. With improvement in the implant surface geometry and surface texture, there is an increase in the bone implant contact area which provides a good primary stability during osseo-integration. PMID:27790598

  5. Short Implants: New Horizon in Implant Dentistry.

    PubMed

    Jain, Neha; Gulati, Manisha; Garg, Meenu; Pathak, Chetan

    2016-09-01

    The choice of implant length is an essential factor in deciding the survival rates of these implants and the overall success of the prosthesis. Placing an implant in the posterior part of the maxilla and mandible has always been very critical due to poor bone quality and quantity. Long implants can be placed in association with complex surgical procedures such as sinus lift and bone augmentation. These techniques are associated with higher cost, increased treatment time and greater morbidity. Hence, there is need for a less invasive treatment option in areas of poor bone quantity and quality. Data related to survival rates of short implants, their design and prosthetic considerations has been compiled and structured in this manuscript with emphasis on the indications, advantages of short implants and critical biomechanical factors to be taken into consideration when choosing to place them. Studies have shown that comparable success rates can be achieved with short implants as those with long implants by decreasing the lateral forces to the prosthesis, eliminating cantilevers, increasing implant surface area and improving implant to abutment connection. Short implants can be considered as an effective treatment alternative in resorbed ridges. Short implants can be considered as a viable treatment option in atrophic ridge cases in order to avoid complex surgical procedures required to place long implants. With improvement in the implant surface geometry and surface texture, there is an increase in the bone implant contact area which provides a good primary stability during osseo-integration.

  6. Melanotic neuroectodermal tumour of infancy: a rare brain tumour of childhood.

    PubMed

    Khan, Muhammad Babar; Soares, Delvene; Tahir, Muhammad Zubair; Kumar, Rajesh; Minhas, Khurram; Bari, Muhammad Ehsan

    2013-05-01

    Melanotic neuroectodermal tumour of infancy is a rare, mostly benign but locally aggressive tumour of neural crest cell origin occurring in infants. The most commonly affected anatomic site is the maxilla. Such tumours of the brain and skull are very rare. We present the case of an 8 months old baby girl whose presenting complaint was a swelling in the scalp for 6 months. She was otherwise asymptomatic. CT imaging confirmed the presence of an osteolytic tumour in the anterior parasagittal skull with dural involvement. The tumour was surgically excised enbloc. The patient has been well at 2 years follow-up without any evidence of recurrence.

  7. Lack of therapeutic gain when low dose rate interstitial radiotherapy is combined with cisplatin in an animal tumour model.

    PubMed

    Pop, L; Levendag, P; van Geel, C; Deurloo, I K; Visser, A

    1992-01-01

    The interaction of cisplatin with low dose rate interstitial radiotherapy was studied in an animal tumour model with a range of dose rats commonly used in clinical low dose rate brachytherapy. Small pieces of R1-rhabdomyosarcoma were implanted subcutaneously in the flanks of female Wag/Rij rats. When the tumour had grown to the desired treatment volume, four afterloading catheters were inserted in the tumour in a square geometry, and a fixed spacing was attained by means of a template. Subsequently, four 2 cm Ir192 wires were inserted. A range of tumour doses of 20-120 Gy at a mean dose rate of 48 cGy/h was applied; 15 mins before the implant an intraperitoneal bolus injection of 3 mg/kg cisplatin was given. For growth delay and cure rate, no modification of the effects of low dose rate brachytherapy by the addition of cisplatin was observed. The observed effects of the combination of cisplatin with low dose rate interstitial radiation in relation to the animal tumour are discussed.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. [Single-cell sequencing and tumour heterogeneity].

    PubMed

    Jordan, Bertrand

    2014-12-01

    The heterogeneity of tumours is now beginning to be documented precisely by single-cell new-generation sequencing. Recently published results on breast tumours show that each of the cells analysed displays a unique pattern of point mutations. This extensive genetic diversity is present before any treatment, and is likely to cause resistance to initially successful targeted therapies.

  14. External beam radiotherapy boosts to reduce the impact caused by edema in prostate permanent seed implants

    NASA Astrophysics Data System (ADS)

    Yue, Ning; Mori, Jonathan; Nath, Ravinder; Heron, Dwight E.; Saiful Huq, M.

    2006-05-01

    In prostate permanent seed implants, it has been shown that edema caused by the surgical procedure decreases dose coverage and hence may reduce treatment efficacy. This reduction in treatment efficacy has been characterized by an increase in tumour cell survival, and biomathematical models have been developed to calculate the tumour cell survival increases in seed implanted prostates of different edema magnitudes and durations. External beam boosts can be utilized to neutralize the negative impact of edema so that originally desired treatment efficacy can be achieved. In this study, a linear quadratic model is used to determine fractionation sizes of the external beam boosts for both 125I and 103Pd seed implants. Calculations were performed for prostates of different edema magnitudes and durations, and for tumour cells of different repair rates and repopulation rates.

  15. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages.

    PubMed

    Guerriero, Jennifer L; Sotayo, Alaba; Ponichtera, Holly E; Castrillon, Jessica A; Pourzia, Alexandra L; Schad, Sara; Johnson, Shawn F; Carrasco, Ruben D; Lazo, Suzan; Bronson, Roderick T; Davis, Scott P; Lobera, Mercedes; Nolan, Michael A; Letai, Anthony

    2017-03-16

    Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success. We hypothesized that pharmacologic modulation of macrophage phenotype could produce an anti-tumour effect. We previously reported that a first-in-class selective class IIa histone deacetylase (HDAC) inhibitor, TMP195, influenced human monocyte responses to the colony-stimulating factors CSF-1 and CSF-2 in vitro. Here, we utilize a macrophage-dependent autochthonous mouse model of breast cancer to demonstrate that in vivo TMP195 treatment alters the tumour microenvironment and reduces tumour burden and pulmonary metastases by modulating macrophage phenotypes. TMP195 induces the recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumours. Furthermore, combining TMP195 with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumour reduction. These data introduce class IIa HDAC inhibition as a means to harness the anti-tumour potential of macrophages to enhance cancer therapy.

  16. p53 tumour suppressor gene expression in pancreatic neuroendocrine tumour cells.

    PubMed Central

    Bartz, C; Ziske, C; Wiedenmann, B; Moelling, K

    1996-01-01

    Neuroendocrine pancreatic tumours grow slower and metastasise later than ductal and acinar carcinomas. The expression of the p53 tumour suppressor gene in pancreatic neuroendocrine tumour cells is unknown. Pancreatic neuroendocrine cell lines (n = 5) and human tumour tissues (n = 19) were studied for changed p53 coding sequence, transcription, and translation. Proliferative activity of tumour cells was determined analysing Ki-67 expression. No mutation in the p53 nucleotide sequence of neuroendocrine tumour cell was found. However, an overexpression of p53 could be detected in neuroendocrine pancreatic tumour cell lines at a protein level. As no p53 mutations were seen, it is suggested that post-translational events can also lead to an overexpression of p53. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8675094

  17. Cooperative tumour cell membrane targeted phototherapy

    NASA Astrophysics Data System (ADS)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  18. Large benign retroperitoneal tumour in pregnancy.

    PubMed

    Berczi, Csaba; Osvath, Peter; Flasko, Tibor

    2015-01-01

    A 31-year-old female was in the 13th week of pregnancy when an abdominal ultrasound examination revealed a large retroperitoneal tumour. Magnetic resonance imaging was carried out and the imaging described a 10-cm mass in diameter extending from the right kidney. Given that the patient was in her first trimester and that there was a suspicion of malignancy, further surgical exploration of the tumour was warranted. During the operation, the tumour was removed, but nephrectomy was not necessary. Histologic analysis of the resected tumour showed a mucinous cystic adenoma, and no signs of malignancy were present. Following the surgery, the pregnancy was otherwise uneventful and further complications did not occur. This case illustrates that surgery is recommended in patients with a retroperitoneal tumour early during a pregnancy, when a malignancy cannot be excluded.

  19. Large benign retroperitoneal tumour in pregnancy

    PubMed Central

    Berczi, Csaba; Osvath, Peter; Flasko, Tibor

    2015-01-01

    A 31-year-old female was in the 13th week of pregnancy when an abdominal ultrasound examination revealed a large retroperitoneal tumour. Magnetic resonance imaging was carried out and the imaging described a 10-cm mass in diameter extending from the right kidney. Given that the patient was in her first trimester and that there was a suspicion of malignancy, further surgical exploration of the tumour was warranted. During the operation, the tumour was removed, but nephrectomy was not necessary. Histologic analysis of the resected tumour showed a mucinous cystic adenoma, and no signs of malignancy were present. Following the surgery, the pregnancy was otherwise uneventful and further complications did not occur. This case illustrates that surgery is recommended in patients with a retroperitoneal tumour early during a pregnancy, when a malignancy cannot be excluded. PMID:26609332

  20. Canine mammary tumour cell lines established in vitro.

    PubMed

    Hellmén, E

    1993-01-01

    Mammary tumours are the most common tumours in the female dog. The tumours have a complex histology and exist in epithelial, mixed and mesenchymal forms. To study the biology of canine mammary tumours, five cell lines have been established and characterized. The results indicate that canine mammary tumours might be derived from mammary stem cells and that the tumour growth is independent of oestrogens. The established canine mammary tumour cell lines will be valuable tools in further studies of the histogenesis and pathogenesis of these tumours.

  1. Adult Wilms' Tumour: Case Report and Review of Literature.

    PubMed

    Modi, Sunny; Tiang, Kor Woi; Inglis, Po; Collins, Stuart

    2016-01-01

    Wilms' tumour (nephroblastoma) is the most common renal tumour in children. Wilms' tumour in adults is extremely rare and has a poorer prognosis than paediatric Wilms' tumour. It is difficult to differentiate adult Wilms' tumour from renal cell carcinoma based on radiological findings alone. The diagnosis in adults is often serendipitous following nephrectomy for presumed renal cell carcinoma. Because of the paucity of literature, there are no standard protocols for the management of adult Wilms' tumour, and therefore, it is managed as per paediatric Wilms' tumour. Herein, we report the case of adult Wilms' tumour in a 43-year-old man, which was diagnosed unexpectedly following nephrectomy for presumed renal cell carcinoma.

  2. Adamantinoma: an unusual bone tumour.

    PubMed

    Roque, Pedro; Mankin, Henry J; Rosenberg, Andrew

    2008-12-01

    Adamantinoma is a rare tumour, which most often affects the tibia and produces lytic and sometimes destructive lesions, which can cause fractures. The lesions occur principally in adults and are more common in males. A small percentage of the patients develop metastases, sometimes quite late in the course. Our institution has treated 42 patients with adamantinomas since 1972 and has evaluated them by imaging studies and histology. The majority of the patients were treated by resection of the lesion and insertion of an intercalary allograft. Only three of the patients died of disease with the time until death ranging from 10 to 17 years. Recurrence occurred in only three patients and the allograft success rate in terms of function was 71% at a mean time of 10 years.

  3. Pulmonary cement embolism in a child following total elbow replacement for primitive neuroectodermal tumour (PNET) of the humerus.

    PubMed

    Ramanathan, Subramaniam; Vora, Tushar; Gulia, Ashish; Mahajan, Abhishek; Desai, Subhash

    2017-05-01

    Pulmonary bone cement embolism (PCE) is an uncommon event occurring after implantation of polymethylmethacrylate (PMMA) in orthopaedic surgeries involving adult patients, more so in the elderly. Its incidence in the paediatric population is extremely rare. We herein describe a case of PCE in a 15-year-old girl, 9 days after she underwent total elbow replacement with PMMA placement for a primitive neuroectodermal tumour (PNET) of the distal humerus. This report describes the occurrence of a common post-operative complication of bone cement embolism in an uncommon scenario of total elbow replacement for a bone tumour in a child, which masqueraded initially as acute pneumonitis.

  4. Nuclear magnetic resonance imaging of tumour growth and neovasculature performance in vivo reveals Grb7 as a novel antiangiogenic target.

    PubMed

    García-Palmero, Irene; López-Larrubia, Pilar; Cerdán, Sebastián; Villalobo, Antonio

    2013-09-01

    Development of neovasculature is a necessary requirement for tumour growth and it provides additional opportunities for therapeutic intervention. However, current antiangiogenic therapies have limited efficacy, mostly because of the development of resistance. Hence, characterization of new antiangiogenic molecular targets is of considerable clinical interest. We report that a calmodulin-binding domain (CaM-BD) deletion mutant of the growth factor receptor bound protein 7 (Grb7) (denoted Grb7Δ) impairs tumour growth and associated angiogenesis in vivo. We implanted glioma C6 cells in rat brains transfected with an enhanced yellow fluorescent protein (EYFP) chimera of Grb7∆, its EYFP-Grb7 wild type counterpart, and EYFP alone. We systematically followed intracerebral growth of the tumours, their cellularity and the functional performance of tumour-associated microvasculature using magnetic resonance imaging, including anatomical T1W and T2W images and functional diffusion and perfusion parameters. Tumours grown from implanted C6 cells expressing EYFP-Grb7Δ developed slower, became smaller and presented lower apparent cellularity than those derived from cells expressing EYFP-Grb7 and EYFP. Vascular perfusion measurements within tumours derived from EYFP-Grb7∆-expressing cells showed significantly lower cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) values. These findings were independently validated by histological and immunohistochemical techniques. Taken together, these findings confirm that the CaM-BD of Grb7 plays an important role in tumour growth and associated angiogenesis in vivo, thus identifying this region of the protein as a novel target for antiangiogenic treatment.

  5. Transsphenoidal surgery for pituitary tumours

    PubMed Central

    Massoud, A; Powell, M; Williams, R; Hindmarsh, P; Brook, C

    1997-01-01

    Accepted 29 January 1997
 OBJECTIVES—Transsphenoidal surgery (TSS) is the preferred method for the excision of pituitary microadenomas in adults. This study was carried out to establish the long term efficacy and safety of TSS in children.
STUDY DESIGN—A 14 year retrospective analysis was carried out on 23 children (16 boys and seven girls), all less than 18 years of age, who had undergone TSS at our centre.
RESULTS—Twenty nine transsphenoidal surgical procedures were carried out. The most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range 0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No death was related to the operation. The most common postoperative complication was diabetes insipidus, which was transient in most patients. Other complications were headaches in two patients and cerebrospinal fluid leaks in two patients. De novo endocrine deficiencies after TSS in children were as follows: three (14%) patients developed panhypopituitarism, eight (73%) developed growth hormone insufficiency, three (14%) developed secondary hypothyroidism, and four (21%) developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five (24%) patients, though all patients received postoperative glucocorticoid treatment until dynamic pituitary tests were performed three months after TSS.
CONCLUSIONS—TSS in children is a safe and effective treatment for pituitary tumours, provided it is performed by surgeons with considerable experience and expertise. Surgical complications are minimal. Postoperative endocrine deficit is considerable, but is only permanent in a small proportion of patients.

 • Transsphenoidal surgery is a safe and effective treatment for pituitary tumours in children • Transsphenoidal surgery should be performed by surgeons with considerable experience and expertise • Surgical complications of

  6. Dental Implant Surgery

    MedlinePlus

    Dental implant surgery Overview By Mayo Clinic Staff Dental implant surgery is a procedure that replaces tooth roots ... that look and function much like real ones. Dental implant surgery can offer a welcome alternative to dentures ...

  7. Hip Implant Systems

    MedlinePlus

    ... Medical Devices Products and Medical Procedures Implants and Prosthetics Metal-on-Metal Hip Implants Hip Implants Share ... femoral head) is removed and replaced with a prosthetic ball made of metal or ceramic, and the ...

  8. Tumour growth of colorectal rat liver metastases is inhibited by hepatic arterial infusion of the mTOR-inhibitor temsirolimus after portal branch ligation.

    PubMed

    Sperling, Jens; Ziemann, Christian; Gittler, Anika; Benz-Weißer, Anna; Menger, Michael D; Kollmar, Otto

    2015-04-01

    Portal branch ligation (PBL) can be performed before major hepatic resection of colorectal liver metastases (mCRC) to increase the remnant liver mass. However, PBL may also stimulate mCRC growth through hepatic arterial hyperperfusion and growth factor release. Herein, we studied whether hepatic arterial infusion (HAI) of the mTOR-inhibitor temsirolimus (Tem) is capable of inhibiting the growth of colorectal liver metastases after PBL. WAG/Rij rats were randomized to four groups (n=6 each) and underwent subcapsular implantation of 5×10(5) CC531 cells into the left liver lobe. The animals of two groups underwent simultaneous PBL of the tumour bearing liver lobe. Ten days later animals underwent a HAI either of temsirolimus (Tem and PBL Tem) or saline solution (Sham and PBL Sham). Tumour size was analyzed at days 10 and 13 using three-dimensional ultrasound. In Sham controls tumour volume increased by 43%. After PBL Sham tumour volume increased by 52%. In contrast, in animals undergoing HAI of temsirolimus the tumour growth was not only completely inhibited, but tumour volume was found decreased, irrespective of PBL. After HAI of temsirolimus immunohistochemistry revealed an increased cleaved caspase-3 activity, indicating stimulation of apoptotic cell death. In parallel temsirolimus treatment was associated with a significant reduction of PECAM-1 positive cells within the tumour tissue, implying a reduced tumour vascularisation. HAI of temsirolimus is capable of inhibiting the growth of CC531 colorectal rat liver metastases also after PBL.

  9. 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

  10. [Cochlear implants].

    PubMed

    Lehnhardt, E; Battmer, R D; Nakahodo, K; Laszig, R

    1986-07-01

    Since the middle of 1984, the HNO-Klinik der Medizinischen Hochschule Hannover has provided deaf adults with a 22-channel cochlear implant (CI) device of Clark-NUCLEUS. The digital working system consists of an implantable stimulator/receiver and an externally worn speech processor. Energy and signals are transmitted transcutaneously via a transmitter coil. During the prevailing 26 operations (April 1986) the electrode array could be inserted at least 17 mm into the cochlea. The threshold and comfort levels of all patients were adjusted very quickly; the dynamic range usually grows during the first postoperative weeks. The individual rehabilitation results vary greatly, but all patients show a significant increase of vowel and consonant comprehension while using the speech processor and an improvement of words understood per minute in speech tracking from lip-reading alone to lip-reading with speech processor. Four months after surgery seven of 17 patients (group I) are able to understand on average 42.7 words per minute by speech tracking without lip-reading. Six patients (group II) recognise 69.2% of vowels and 42.5% of consonants by speech processor alone. Four patients (group III) can correctly repeat only vowels (52.3%) without lip-reading, but using the speech processor together with lip reading they have an improvement in consonant understanding of 37.9% and under freefield conditions they are able to understand up to 17.8% numbers of the Freiburg speech test.

  11. 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

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

    PubMed

    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.

  13. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid.

    PubMed

    Colegio, Oscar R; Chu, Ngoc-Quynh; Szabo, Alison L; Chu, Thach; Rhebergen, Anne Marie; Jairam, Vikram; Cyrus, Nika; Brokowski, Carolyn E; Eisenbarth, Stephanie C; Phillips, Gillian M; Cline, Gary W; Phillips, Andrew J; Medzhitov, Ruslan

    2014-09-25

    Macrophages have an important role in the maintenance of tissue homeostasis. To perform this function, macrophages must have the capacity to monitor the functional states of their 'client cells': namely, the parenchymal cells in the various tissues in which macrophages reside. Tumours exhibit many features of abnormally developed organs, including tissue architecture and cellular composition. Similarly to macrophages in normal tissues and organs, macrophages in tumours (tumour-associated macrophages) perform some key homeostatic functions that allow tumour maintenance and growth. However, the signals involved in communication between tumours and macrophages are poorly defined. Here we show that lactic acid produced by tumour cells, as a by-product of aerobic or anaerobic glycolysis, has a critical function in signalling, through inducing the expression of vascular endothelial growth factor and the M2-like polarization of tumour-associated macrophages. Furthermore, we demonstrate that this effect of lactic acid is mediated by hypoxia-inducible factor 1α (HIF1α). Finally, we show that the lactate-induced expression of arginase 1 by macrophages has an important role in tumour growth. Collectively, these findings identify a mechanism of communication between macrophages and their client cells, including tumour cells. This communication most probably evolved to promote homeostasis in normal tissues but can also be engaged in tumours to promote their growth.

  14. Untangling the model muddle: Empirical tumour growth in Tasmanian devil facial tumour disease.

    PubMed

    Hamede, Rodrigo K; Beeton, Nicholas J; Carver, Scott; Jones, Menna E

    2017-07-24

    A pressing and unresolved topic in cancer research is how tumours grow in the absence of treatment. Despite advances in cancer biology, therapeutic and diagnostic technologies, there is limited knowledge regarding the fundamental growth and developmental patterns in solid tumours. In this ten year study, we estimated growth curves in Tasmanian devil facial tumours, a clonal transmissible cancer, in males and females with two different karyotypes (diploid, tetraploid) and facial locations (mucosal, dermal), using established differential equation models and model selection. Logistic growth was the most parsimonious model for diploid, tetraploid and mucosal tumours, with less model certainty for dermal tumours. Estimates of daily proportional tumour growth rate per day (95% Bayesian CIs) varied with ploidy and location [diploid 0.016 (0.014-0.020), tetraploid 0.026 (0.020-0.033), mucosal 0.013 (0.011-0.015), dermal 0.020 (0.016-0.024)]. Final tumour size (cm(3)) also varied, particularly the upper credible interval owing to host mortality as tumours approached maximum volume [diploid 364 (136-2,475), tetraploid 172 (100-305), dermal 226 (134-471)]. To our knowledge, these are the first empirical estimates of tumour growth in the absence of treatment in a wild population. Through this animal-cancer system our findings may enhance understanding of how tumour properties interact with growth dynamics in other types of cancer.

  15. Rare benign tumours of the nipple.

    PubMed

    Spyropoulou, G A; Pavlidis, L; Trakatelli, M; Athanasiou, E; Pazarli, E; Sotiriadis, D; Demiri, E

    2015-01-01

    Benign lesions of the breast in total are much more frequent than malignant ones. However, there are no epidemiologic data on the prevalence of benign or malignant tumours of the nipple, and the bibliography on benign nipple tumours in general is limited. To present some rare cases of benign nipple tumours and review the literature. Four cases of rare benign nipple tumours: neurofibromas, wart, leiomyoma and milium are presented. The literature search on benign nipple tumours was performed using MEDLINE, Pubmed, and Cochrane databases with limits: English language, human species and available abstract. The keyword used was 'benign nipple tumours'. The initial search retrieved 337 articles. The papers were reviewed and the articles that referred to benign lesions that appeared at the nipple specifically were identified. Different entities that were described included: neurofibroma, leiomyoma, milium, florid papillomatosis, syringomatous adenoma, nevoid hyperkeratosis, fibroma, pseudolymphoma and haemangioma. Differential diagnosis of benign tumours of the nipple can be demanding for the physicians. Many of the symptoms and signs like pruritus, serosanguinous discharge, lichenification, erosion and nodular enlargement are produced by either malignant or benign nipple lesions. Radiology can be unclear in the diagnosis of nipple abnormalities. Histological examination of the lesion can be the only definite answer in these cases. © 2014 European Academy of Dermatology and Venereology.

  16. Imaging of retinal and choroidal vascular tumours

    PubMed Central

    Heimann, H; Jmor, F; Damato, B

    2013-01-01

    The most common intraocular vascular tumours are choroidal haemangiomas, vasoproliferative tumours, and retinal haemangioblastomas. Rarer conditions include cavernous retinal angioma and arteriovenous malformations. Options for ablating the tumour include photodynamic therapy, argon laser photocoagulation, trans-scleral diathermy, cryotherapy, anti-angiogenic agents, plaque radiotherapy, and proton beam radiotherapy. Secondary effects are common and include retinal exudates, macular oedema, epiretinal membranes, retinal fibrosis, as well as serous and tractional retinal detachment, which are treated using standard methods (ie, intravitreal anti-angiogenic agents or steroids as well as vitreoretinal procedures, such as epiretinal membrane peeling and release of retinal traction). The detection, diagnosis, and monitoring of vascular tumours and their complications have improved considerably thanks to advances in imaging. These include spectral domain and enhanced depth imaging optical coherence tomography (SD-OCT and EDI-OCT, respectively), wide-angle photography and angiography as well as wide-angle fundus autofluorescence. Such novel imaging has provided new diagnostic clues and has profoundly influenced therapeutic strategies so that vascular tumours and secondary effects are now treated concurrently instead of sequentially, enhancing any opportunities for conserving vision and the eye. In this review, we describe how SD-OCT, EDI-OCT, autofluorescence, wide-angle photography and wide-angle angiography have facilitated the evaluation of eyes with the more common vascular tumours, that is, choroidal haemangioma, retinal vasoproliferative tumours, and retinal haemangioblastoma. PMID:23196648

  17. 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.

  18. Paediatric extracranial germ-cell tumours.

    PubMed

    Shaikh, Furqan; Murray, Matthew J; Amatruda, James F; Coleman, Nicholas; Nicholson, James C; Hale, Juliet P; Pashankar, Farzana; Stoneham, Sara J; Poynter, Jenny N; Olson, Thomas A; Billmire, Deborah F; Stark, Daniel; Rodriguez-Galindo, Carlos; Frazier, A Lindsay

    2016-04-01

    Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 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.

  20. A model of vascular tumour growth in mice combining longitudinal tumour size data with histological biomarkers.

    PubMed

    Ribba, Benjamin; Watkin, Emmanuel; Tod, Michel; Girard, Pascal; Grenier, Emmanuel; You, Benoît; Giraudo, Enrico; Freyer, Gilles

    2011-02-01

    Optimising the delivery of antiangiogenic drugs requires the development of drug-disease models of vascular tumour growth that incorporate histological data indicative of cytostatic action. In this study, we formulated a model to analyse the dynamics of tumour progression in nude mice xenografted with HT29 or HCT116 colorectal cancer cells. In 30 mice, tumour size was periodically measured, and percentages of hypoxic and necrotic tissue were assessed using immunohistochemistry techniques on tumour samples after euthanasia. The simultaneous analysis of histological data together with longitudinal tumour size data prompted the development of a semi-mechanistic model integrating random effects of parameters. In this model, the peripheral non-hypoxic tissue proliferates according to a generalised-logistic equation where the maximal tumour size is represented by a variable called 'carrying capacity'. The ratio of the whole tumour size to the carrying capacity was used to define the hypoxic stress. As this stress increases, non-hypoxic tissue turns hypoxic. Hypoxic tissue does not stop proliferating, but hypoxia constitutes a transient stage before the tissue becomes necrotic. As the tumour grows, the carrying capacity increases owing to the process of angiogenesis. The model is shown to correctly predict tumour growth dynamics as well as percentages of necrotic and hypoxic tissues within the tumour. We show how the model can be used as a theoretical tool to investigate the effects of antiangiogenic treatments on tumour growth. This model provides a tool to analyse tumour size data in combination with histological biomarkers such as the percentages of hypoxic and necrotic tissue and is shown to be useful for gaining insight into the effects of antiangiogenic drugs on tumour growth and composition.

  1. Implant marketing: cost effective implant dentistry.

    PubMed

    Wohrle, P S; Levin, R P

    1996-01-01

    The application of the KAL-Technique to the field of implant dentistry allows both patients and dental practices to benefit. It is an exciting advance that decreases frustration and stress in providing implant procedures and lowers overall costs. Professionals using the KAL-Technique report significant predictability in achieving passive framework fit. They are also lowering overall cost of implant cases, which increases the number of patients who can accept implant treatment. It has been well established that the more individuals in a practice that receive implants, the more referrals a practice will gain. This is because implant patients find tremendous advances in the quality of life, and do not hesitate to tell others who can take advantage of this opportunity. Implant dentistry is one of the fastest growing fields in dentistry today. While some other areas of dentistry begin to decline in volume and need, implant dentistry provides the opportunity to keep practices strong and to insure long-term success.

  2. Suppression of murine tumour growth through CD8(+) cytotoxic T lymphocytes via activated DEC-205(+) dendritic cells by sequential administration of α-galactosylceramide in vivo.

    PubMed

    Kogo, Hideki; Shimizu, Masumi; Negishi, Yasuyuki; Uchida, Eiji; Takahashi, Hidemi

    2017-07-01

    Cancer immunity is mediated through the effective priming and activation of tumour-specific class I MHC molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumour antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumour-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction. Hepa1-6-1 cells were established from the mouse hepatoma cell line Hepa1-6; these cells grow continuously after subcutaneous implantation into syngeneic C57BL/6 (B6) mice and do not prime CD8(+) CTLs. In this study, we show that the growth of ongoing tumours was suppressed by activated CD8(+) CTLs with tumour-specific cytotoxicity through the administration of the glycolipid α-galactosylceramide (α-GalCer), which is a compound known to stimulate invariant natural killer T (iNKT) cells and selectively activate DEC-205(+) DCs. Moreover, we demonstrated that sequential repetitive intraperitoneal inoculation with α-GalCer every 48 hr appeared to convert tolerogenic DEC-205(+) DCs into immunogenic DCs with a higher expression of co-stimulatory molecules and a stronger cross-presentation capacity, which primed CTL precursors and induced tumour-specific CD8(+) CTLs within the tumour environment without activating iNKT cells. These findings provide a new basis for cancer immunotherapy to convert tolerogenic DEC-205(+) DCs within tumours into immunogenic DCs through the sequential administration of an immuno-potent lipid/glycolipid, and then activated immunogenic DCs with sufficient expression of co-stimulatory molecules prime and activate tumour-specific CD8(+) CTLs within the tumour to control tumour growth. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

  3. Gestational trophoblastic tumours: an update for 2014.

    PubMed

    Froeling, Fieke E M; Seckl, Michael J

    2014-11-01

    Gestational trophoblastic disease describes a variety of pregnancy-related diseases including the premalignant conditions of a partial and complete hydatidiform mole and the malignant disorders of invasive mole, choriocarcinoma and the rare placental-site trophoblastic tumour and epithelioid trophoblastic tumour. The availability of a highly sensitive tumour marker in the form of human chorionic gonadotrophin, the chemosensitive character of the disease with effective treatment strategies and centralization of care of a rare group of diseases has resulted in excellent survival rates, which can exceed 98 %. This review gives a general overview of gestational trophoblastic disease, the most recent insights in aetiology and pathology and a summary of the different management strategies.

  4. 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

  5. Transoral robotic surgery for retromolar trigone tumours.

    PubMed

    Durmus, K; Apuhan, T; Ozer, E

    2013-12-01

    The retromolar trigone is a challenging transoral surgical site due to the difficulty of visualization. Our aim is to report a new technique of transoral robotic resection of retromolar trigone tumours. We present three patients with retromolar trigone tumours with pathological diagnosis of squamous cell carcinoma who underwent successful transoral robotic resection. Robotic retromolar trigone resection and concurrent supraomohyoid neck dissections were performed in all patients without any complication. In conclusion, transoral robotic surgery is a safe and feasible technique for resection of malignant retromolar trigone tumours with minimal complications and favourable outcomes.

  6. Contrast‐enhanced ultrasound of pancreatic tumours

    PubMed Central

    D'Onofrio, Mirko; Crosara, Stefano; Dal Corso, Flavia; Barbi, Emilio; Canestrini, Stefano; Mucelli, Roberto Pozzi

    2015-01-01

    Abstract Indication/purpose: To review contrast‐enhanced ultrasound features of the most common pancreatic tumours. Methods: Contrast‐enhanced ultrasound (CEUS) can provide distinctive features of pancreatic tumours that are reported in the present paper, providing radiologic‐pathological correlations and clarifying the main differential diagnosis. Conclusion: Contrast‐enhanced ultrasound plays a well‐established role in the evaluation of pancreatic tumours. When possible, CEUS should be always performed after the initial US diagnosis, in order to improve the accuracy of the first line examination. PMID:28191218

  7. Pulmonary tumour microembolism clinically mimicking alveolitis

    PubMed Central

    Lo, A W I; Tse, G M K; Chu, W C W; Chan, A B W

    2003-01-01

    A 56 year old man with previously unsuspected recurrence of squamous cell carcinoma of the oesophagus presented with dyspnoea. Bronchoscopy and computed tomography suggested bronchopneumonic changes with an infectious cause. He suffered a rapidly deteriorating course and died despite active treatment, including antibiotics and mechanical ventilation. Necropsy revealed a florid pulmonary tumour microembolism mimicking alveolitis. No bronchopneumonia was seen. The emboli arose from loosely attached tumour vegetations in the tricuspid valve. In a patient with known malignancy, tumour microembolism should be considered as an uncommon cause of rapid respiratory failure, refractory to antibiotic treatment. PMID:14600135

  8. Modes of invasion during tumour dissemination.

    PubMed

    Pandya, Pahini; Orgaz, Jose L; Sanz-Moreno, Victoria

    2017-01-01

    Cancer cell migration and invasion underlie metastatic dissemination, one of the major problems in cancer. Tumour cells exhibit a striking variety of invasion strategies. Importantly, cancer cells can switch between invasion modes in order to cope with challenging environments. This ability to switch migratory modes or plasticity highlights the challenges behind antimetastasis therapy design. In this Review, we present current knowledge on different tumour invasion strategies, the determinants controlling plasticity and arising therapeutic opportunities. We propose that targeting master regulators controlling plasticity is needed to hinder tumour dissemination and metastasis. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  9. Tumour size, tumour complexity, and surgical approach are associated with nephrectomy type in small renal cortical tumours treated electively.

    PubMed

    Broughton, Gregory J; Clark, Peter E; Barocas, Daniel A; Cookson, Michael S; Smith, Joseph A; Herrell, S Duke; Chang, Sam S

    2012-06-01

    Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Although the benefits of nephron-sparing renal cortical tumour treatments are now widely accepted and have robust data supporting their oncological efficacy, safety, and positive effect on medium- and long-term renal function, the decision to perform partial nephrectomy (PN) remains a complex interaction between several competing factors. Various patient factors, e.g. comorbid conditions, age, body habitus, patient preference, etc. may effect this decision. Then there are the preferences of the surgeon him- or herself, including faculty with different operative techniques and surgical approaches, which may lead to one treatment decision over another. Finally, the anatomy of the tumour itself, i.e. the complexity of the tumour within the kidney and anatomical relationships within the organ, is intuitively critical to a surgeon's assessment of resectability. There is very little published data indicating which of the multitude of clinical variables have the greatest impact on the decision to perform PN. Most previous investigations into the subject have focused on either imperative or relative indications for PN (i.e. solitary kidney, bilateral renal masses, and multifocal tumours) or have used maximal tumour diameter (i.e. tumour size) alone in their assessment of the clinical variables associated with PN use. To identify preoperative variables associated with choice of partial nephrectomy (PN) vs radical nephrectomy (RN). Between January 2004 and June 2008, 203 patients were treated for clinical T1a renal cortical tumours. Of these, 154 (75.8%) had all data available and form the analytic cohort. Patients were categorized into two groups, PN and RN, based on preoperative treatment plan. Patient-, procedure-, and tumour-related variables, together with tumour complexity (based on the R.E.N.A.L Nephrometry Score [RENAL-NS]) were evaluated for their

  10. Odontogenic ghost cell tumour with clear cell components: clear cell odontogenic ghost cell tumour?

    PubMed

    Yoon, Jung Hoon; Ahn, Sang Gun; Kim, Su Gwan; Kim, Jin

    2004-07-01

    A case of odontogenic ghost cell tumour (OGCT) with clear cell components was encountered in the mandible of a 63-year-old man. The tumour revealed ameloblastomatous-type epithelial components accompanied by clusters of ghost cells and dentinoid juxtaposed to the odontogenic epithelium. In addition, some areas of the tumour tissue showed sheets and islands of clear, glycogen containing epithelial cells, which were separated by a thin fibrous connective tissue stroma. Both ameloblastic and clear cells exhibited positive immunoreactivities for cytokeratin 19 and AE1/3. It is not known whether this tumour represents a clear cell change of a pre-existing OGCT or a separate and distinct neoplasm derived de novo from the odontogenic epithelium. This tumour was given the term 'clear cell OGCT' because it captures the clear cell components, which is one of the most prominent distinguishing features of the tumour.

  11. Bilayer Implants

    PubMed Central

    Schagemann, Jan C.; Rudert, Nicola; Taylor, Michelle E.; Sim, Sotcheadt; Quenneville, Eric; Garon, Martin; Klinger, Mathias; Buschmann, Michael D.; Mittelstaedt, Hagen

    2016-01-01

    Objective To compare the regenerative capacity of 2 distinct bilayer implants for the restoration of osteochondral defects in a preliminary sheep model. Methods Critical sized osteochondral defects were treated with a novel biomimetic poly-ε-caprolactone (PCL) implant (Treatment No. 2; n = 6) or a combination of Chondro-Gide and Orthoss (Treatment No. 1; n = 6). At 19 months postoperation, repair tissue (n = 5 each) was analyzed for histology and biochemistry. Electromechanical mappings (Arthro-BST) were performed ex vivo. Results Histological scores, electromechanical quantitative parameter values, dsDNA and sGAG contents measured at the repair sites were statistically lower than those obtained from the contralateral surfaces. Electromechanical mappings and higher dsDNA and sGAG/weight levels indicated better regeneration for Treatment No. 1. However, these differences were not significant. For both treatments, Arthro-BST revealed early signs of degeneration of the cartilage surrounding the repair site. The International Cartilage Repair Society II histological scores of the repair tissue were significantly higher for Treatment No. 1 (10.3 ± 0.38 SE) compared to Treatment No. 2 (8.7 ± 0.45 SE). The parameters cell morphology and vascularization scored highest whereas tidemark formation scored the lowest. Conclusion There was cell infiltration and regeneration of bone and cartilage. However, repair was incomplete and fibrocartilaginous. There were no significant differences in the quality of regeneration between the treatments except in some histological scoring categories. The results from Arthro-BST measurements were comparable to traditional invasive/destructive methods of measuring quality of cartilage repair. PMID:27688843

  12. Tumour necrosis factor alpha increases melphalan concentration in tumour tissue after isolated limb perfusion

    PubMed Central

    de Wilt, J H W; ten Hagen, T L M; de Boeck, G; van Tiel, S T; de Bruijn, E A; Eggermont, A M M

    2000-01-01

    Several possible mechanisms for the synergistic anti-tumour effects between tumour necrosis factor alpha (TNF-α) and melphalan after isolated limb perfusion (ILP) have been presented. We found a significant sixfold increase in melphalan tumour tissue concentration after ILP when TNF-α was added to the perfusate, which provides a straightforward explanation for the observed synergism between melphalan and TNF-α in ILP. © 2000 Cancer Research Campaign PMID:10737379

  13. Tumour angiogenic activity and vascular survival ability in bladder carcinoma.

    PubMed

    Papadopoulos, I; Giatromanolaki, A; Koukourakis, M I; Sivridis, E

    2004-03-01

    Tumour angiogenic activity (TAA) is an important prognostic factor in many human tumours, including transitional cell carcinomas of the urinary bladder. The new tumour vessels are formed in the invading tumour front. This peripheral tumour area is internalised as soon as the growing tumour forms a new front. To investigate and compare TAA with the ability of the tumour vasculature to survive (VSA) in inner tumour areas. Fifty one cystectomy specimens with transitional cell carcinoma of the urinary bladder were studied. Sections were stained immunohistochemically for endothelial cells and proliferation activity, using the monoclonal antibodies CD31 and MIB-1, respectively. TAA was studied at the invading tumour edge-designated as the mean number of blood vessels in three "hot spots" at this site. VSA was assessed by comparing the vascular density in peripheral and inner tumour areas. High TAA at the invading tumour edge significantly correlated with lymph node involvement, but not with patient survival. Extensive lymphocytic infiltration was more frequent in tumours with high TAA. VSA was significantly higher in tumours of high proliferation index, high histological grade, advanced T stage, and poor prognosis. However, there was no association with metastasis to regional lymph nodes. VSA and TAA provide a more complete profile of the tumour vasculature and are associated with aggressive tumour behaviour in transitional cell carcinomas of the urinary bladder. The qualitative information provided by VSA may be important for the identification of angiogenic tumours with differential responses to various antiangiogenic treatments.

  14. Ovarian yolk sac tumour in a girl - case report.

    PubMed

    Sharma, Charu; Shah, Hemanshi; Sisodiya Shenoy, Neha; Makhija, Deepa; Waghmare, Mukta

    2017-01-01

    Yolk sac tumours are rare ovarian malignancies accounting for less than 1% of malignant ovarian germ cell tumours. They are mostly seen in adolescents and young women and are usually unilateral making fertility preservation imperative. Raised alpha-feto protein level is the hallmark of this tumour. We describe stage III yolk sac tumour in a girl child.

  15. [Application of tumour markers in clinical practice].

    PubMed

    Keuren, Jeffrey F W; Thomas, Chris M G; Bonfrèr, J M G Hans; Sweep, C G J Fred; Boonstra, Joke G

    2009-01-01

    Usefully requesting and applying serum tumour markers in diagnosis and treatment can be difficult. It should be noted that tumour markers are used for varying purposes: screening, diagnosis, staging and prognostic evaluation, detection of recurrence and treatment monitoring. Due to the poor sensitivity and specificity of current tumour markers, most are not suitable for screening an asymptomatic population. Further, the benefits of an improved prognosis by early detection should be weighed against a poorer quality of life and the cost of substantial over-diagnosis and over-treatment. Serum tumour markers are particularly applicable in treatment monitoring and detection of recurrence. Sometimes they can be used to support the diagnostic process and give useful prognostic information.

  16. 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

  17. [Malignant phyllodes tumour : a case report].

    PubMed

    Radermacher, J; Burlet, O; Sylvestre, R M; Wetz, P; Delvenne, Ph

    2016-11-01

    A 28 year old woman has suffered over the previous month from a post-traumatic swelling sensation of the left breast. Ultrasonography demonstrates a 9 cm, sharply-cut, rounded, hypo-echogenic lesion. Surgery is performed, with the hypothesis of an haematoma. The pathological analysis of the lesion shows a malignant phyllodes tumour with heterologous rhabdomyosarcomatous features. No metastasis is found. A radical mastectomy is performed and the patient benefits from an adjuvant radio-chemotherapy. Phyllodes tumours represent up to 1 % of all mammary cancers, with 10-20 % of malignant lesions. These tumours behave differently from usual breast cancers. This atypical case, arising in a traumatic context, provides the opportunity to discuss the treatment and classification of phyllodes tumours of the breast.

  18. Peripheral primitive neuroectodermal tumour in a dog.

    PubMed

    Junginger, J; Röthlisberger, A; Lehmbecker, A; Stein, V M; Ludwig, D C; Baumgärtner, W; Seehusen, F

    2013-11-01

    A 1-year-old German shepherd dog was presented with paraparesis quickly progressing to paraplegia. Magnetic resonance imaging revealed a large mass beneath the thoracolumbar vertebral column infiltrating the spinal canal and resulting in severe extradural compression of the spinal cord. Microscopically, this comprised a cell-rich unencapsulated tumour supported by fine bands of a fibrovascular stroma and occasionally forming primitive rosettes. Immunohistochemistry showed the tumour cells to express synaptophysin and neuron-specific enolase. Ultrastructurally, the neoplastic cells had low to moderate numbers of intracytoplasmic neurosecretory granules. A peripheral primitive neuroectodermal tumour was diagnosed. This is a rare embryonal tumour of neural origin that may have arisen from adrenal medulla, autonomic ganglia or peripheral nerves.

  19. 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

  20. 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

  1. Simulating tumour removal in neurosurgery.

    PubMed

    Radetzky, A; Rudolph, M

    2001-12-01

    In this article the software system ROBO-SIM is described. ROBO-SIM is a planning and simulation tool for minimally invasive neurosurgery. Different to the most other simulation tools, ROBO-SIM is able to use actual patient's datasets for simulation. Same as in real neurosurgery a planning step, which provides more functionality as up-to-date planning systems on the market, is performed before undergoing the simulated operation. The planning steps include the definition of the trepanation point for entry into the skull and the target point within the depth of the brain, checking the surgical track and doing virtual trepanations (virtual craniotomy). For use with an intra-operative active manipulator, which is guided by the surgeon during real surgery (robotic surgery), go- and non-go-areas can be defined. During operation, the robot restricts the surgeon from leaving these go-areas. After planning, an additional simulation system, which is understood as an extension to the planning step, is used to simulate whole surgical interventions directly on the patient's anatomy basing on the planning data and by using the same instruments as for the real intervention. First tests with ROBO-SIM are performed on a phantom developed for this purpose and on actual patient's datasets with ventricular tumours.

  2. Keratocystic odontogenic tumour: systematic review

    PubMed Central

    MacDonald-Jankowski, D S

    2011-01-01

    Objectives The aim of this review is to evaluate the principal clinical and conventional radiographic features of non-syndromic keratocystic odontogenic tumour (KCOT) by systematic review (SR), and to compare the frequencies between four global groups. Methods The databases searched were the PubMed interface of Medline and LILACS. Only those reports of KCOTs that occurred in a series of consecutive cases, in the reporting authors' caseload, were considered. Results 51 reports, of 49 series of cases, were included in the SR. 11 SR-included series were in languages other than English. KCOTs affected males more frequently and were three times more prevalent in the mandible. Although the mean age at first presentation was 37 years, the largest proportion of cases first presented in the third decade. The main symptom was swelling. Over a third were found incidentally. Nearly two-thirds displayed buccolingual expansion. Over a quarter of cases recurred. Only a quarter of all SR-included reported series of cases included details of at least one radiological feature. The East Asian global group presented significantly as well-defined, even corticated, multilocular radiolucencies with buccolingual expansion. The KCOTs affecting the Western global group significantly displayed an association with unerupted teeth. Conclusions Long-term follow-up of large series that would have revealed detailed radiographic description and long-term outcomes of non-syndromic KCOT was lacking. PMID:21159911

  3. Calcifying Epithelial Odontogenic Tumour of the Mandible: An Unusually Aggressive Presentation of an Indolent Tumour

    PubMed Central

    Dev, DP Arul; Michael, Manoj Joseph; Akhilesh, AV; Das, Bindu

    2016-01-01

    Calcifying Epithelial Odontogenic Tumour (CEOT) or Pindborg tumour is a rare odontogenic tumour of epithelial origin. They constitute less than 1% of odontogenic tumours. Intra-ossseous variant of CEOT are more common compared to extra-osseous variant. Although benign, these can exhibit deceptively aggressive presentation. Here we report a rare case of CEOT in a 36-year-old female patient who presented with aggressive intra-osseous lesion with cortical breach and exuberant soft tissue proliferation. The lesion was treated with resection and reconstructed with titanium reconstruction plate. PMID:27790590

  4. Stromal Claudin14-Heterozygosity, but Not Deletion, Increases Tumour Blood Leakage without Affecting Tumour Growth

    PubMed Central

    Baker, Marianne; Reynolds, Louise E.; Robinson, Stephen D.; Lees, Delphine M.; Parsons, Maddy; Elia, George; Hodivala-Dilke, Kairbaan

    2013-01-01

    The maintenance of endothelial cell-cell junctions is vital for the control of blood vessel leakage and is known to be important in the growth and maturation of new blood vessels during angiogenesis. Here we have investigated the role of a tight junction molecule, Claudin14, in tumour blood vessel leakage, angiogenesis and tumour growth. Using syngeneic tumour models our results showed that genetic ablation of Claudin14 was not sufficient to affect tumour blood vessel morphology or function. However, and surprisingly, Claudin14-heterozygous mice displayed several blood vessel-related phenotypes including: disruption of ZO-1-positive cell-cell junctions in tumour blood vessels; abnormal distribution of basement membrane laminin around tumour blood vessels; increased intratumoural leakage and decreased intratumoural hypoxia. Additionally, although total numbers of tumour blood vessels were increased in Claudin14-heterozygous mice, and in VEGF-stimulated angiogenesis ex vivo, the number of lumenated vessels was not changed between genotypes and this correlated with no difference in syngeneic tumour growth between wild-type, Claudin14-heterozygous and Claudin14-null mice. Lastly, Claudin14-heterozygosity, but not complete deficiency, also enhanced endothelial cell proliferation significantly. These data establish a new role for Claudin14 in the regulation of tumour blood vessel integrity and angiogenesis that is evident only after the partial loss of this molecule in Claudin14-heterozyous mice but not in Claudin14-null mice. PMID:23675413

  5. Primary primitive neuroectodermal tumour of the kidney in adults.

    PubMed

    Verma, Ritu; Singhal, Mitali; Pandey, Rakesh

    2013-03-04

    Primitive neuroectodermal tumour (PNET) is a neural crest tumour derived from neuroectoderm. Renal PNET is a very rare tumour occurring during childhood or adolescence. We report two cases of PNET involving kidney in adults. Presenting signs and symptoms include abdominal/flank pain and/or haematuria. Microscopy reveals the tumour consisted of small round cells with round nuclei and scant cytoplasm. Diagnosis was confirmed by immunohistochemistry with diffuse membranous positivity of tumour cells with CD99. As these tumours have an aggressive clinical course with rapid death in many reported cases, it is important to differentiate them from other small round-cell tumours.

  6. Tumour-targeted nanomedicines: principles and practice

    PubMed Central

    Lammers, T; Hennink, W E; Storm, G

    2008-01-01

    Drug targeting systems are nanometre-sized carrier materials designed for improving the biodistribution of systemically applied (chemo)therapeutics. Various different tumour-targeted nanomedicines have been evaluated over the years, and clear evidence is currently available for substantial improvement of the therapeutic index of anticancer agents. Here, we briefly summarise the most important targeting systems and strategies, and discuss recent advances and future directions in the development of tumour-targeted nanomedicines. PMID:18648371

  7. Watery diarrhoea and an islet cell tumour

    PubMed Central

    Hindle, W.; McBrien, D. J.; Creamer, B.

    1964-01-01

    It is suggested that there are two hormonal syndromes associated with noninsulin-secreting islet cell tumours and this case is an example of the non-gastrin-secreting type with watery diarrhoea and hypokalaemia. The patient had histamine-fast achlorhydria and a normal gastric biopsy and no gastrin was recovered from the tumour tissue. The watery diarrhoea was isosmotic with plasma and was increased by an intravenous saline load. There was a dramatic response to steroids. PMID:14209921

  8. Clinicopathological study of canine transmissible venereal tumour in leishmaniotic dogs.

    PubMed

    Marino, G; Gaglio, G; Zanghì, A

    2012-06-01

    Canine transmissible venereal tumour is occasionally observed in leishmaniotic dogs, and Leishmania amastigotes can be harboured in canine transmissible venereal tumour cells. The aim of this paper was to investigate the clinicopathological significance of the association of both diseases. Nineteen dogs affected by canine transmissible venereal tumour and canine leishmaniasis were studied retrospectively. In these dogs, the tumour manifested a large size and often aggressive behaviour (42%) and no predictive sign of spontaneous regression was observed. Sporadic Leishmania amastigotes were found within the canine transmissible venereal tumour in three cases, probably transported by infected macrophages often infiltrating the tumour. A high Leishmania parasitisation of canine transmissible venereal tumour was observed in two other cases and verified by immunohistochemistry. Canine transmissible venereal tumour is a tumour of the dog able to harbour a large number of Leishmania parasites. Alternatively, the systemic disease (canine leishmaniasis) may lower the immune defence against malignancy (canine transmissible venereal tumour). © 2012 British Small Animal Veterinary Association.

  9. Multiscale modelling and nonlinear simulation of vascular tumour growth

    PubMed Central

    Macklin, Paul; Anderson, Alexander R. A.; Chaplain, Mark A. J.; Cristini, Vittorio

    2011-01-01

    In this article, we present a new multiscale mathematical model for solid tumour growth which couples an improved model of tumour invasion with a model of tumour-induced angiogenesis. We perform nonlinear simulations of the multi-scale model that demonstrate the importance of the coupling between the development and remodeling of the vascular network, the blood flow through the network and the tumour progression. Consistent with clinical observations, the hydrostatic stress generated by tumour cell proliferation shuts down large portions of the vascular network dramatically affecting the flow, the subsequent network remodeling, the delivery of nutrients to the tumour and the subsequent tumour progression. In addition, extracellular matrix degradation by tumour cells is seen to have a dramatic affect on both the development of the vascular network and the growth response of the tumour. In particular, the newly developing vessels tend to encapsulate, rather than penetrate, the tumour and are thus less effective in delivering nutrients. PMID:18781303

  10. A dynamical model of tumour immunotherapy.

    PubMed

    Frascoli, Federico; Kim, Peter S; Hughes, Barry D; Landman, Kerry A

    2014-07-01

    A coupled ordinary differential equation model of tumour-immune dynamics is presented and analysed. The model accounts for biological and clinical factors which regulate the interaction rates of cytotoxic T lymphocytes on the surface of the tumour mass. A phase plane analysis demonstrates that competition between tumour cells and lymphocytes can result in tumour eradication, perpetual oscillations, or unbounded solutions. To investigate the dependence of the dynamic behaviour on model parameters, the equations are solved analytically and conditions for unbounded versus bounded solutions are discussed. An analytic characterisation of the basin of attraction for oscillatory orbits is given. It is also shown that the tumour shape, characterised by a surface area to volume scaling factor, influences the size of the basin, with significant consequences for therapy design. The findings reveal that the tumour volume must surpass a threshold size that depends on lymphocyte parameters for the cancer to be completely eliminated. A semi-analytic procedure to calculate oscillation periods and determine their sensitivity to model parameters is also presented. Numerical results show that the period of oscillations exhibits notable nonlinear dependence on biologically relevant conditions.

  11. Smooth muscle tumours of the alimentary tract.

    PubMed Central

    Diamond, T.; Danton, M. H.; Parks, T. G.

    1990-01-01

    Neoplasms arising from smooth muscle of the gastrointestinal (GI) tract are uncommon, comprising only 1% of gastrointestinal tumours. A total of 51 cases of smooth muscle tumour of the GI tract were analysed; 44 leiomyomas and 7 leiomyosarcomas. Lesions occurred in all areas from the oesophagus to the rectum, the stomach being the commonest site. Thirty-six patients had clinical features referable to the tumour. The tumour was detected during investigation or management of an unrelated disease process in 15 patients. The clinical presentation varied depending on tumour location, but abdominal pain and GI bleeding were the commonest presenting symptoms. The lesion was demonstrated preoperatively, mainly by endoscopy and barium studies, in 27 patients. Surgical excision was the treatment of choice, where possible. There was no recurrence in the leiomyoma group but four patients died in the leiomyosarcoma group. Although rare, smooth muscle tumours should be considered in situations where clinical presentation and investigations are not suggestive of any common GI disorder. The preoperative assessment and diagnosis is difficult because of the variability in clinical features and their inaccessibility to routine GI investigation. It is recommended that, where possible, the lesion, whether symptomatic or discovered incidentally, should be excised completely to achieve a cure and prevent future complications. Images Figure 3 Figure 4 PMID:2221768

  12. [Bilateral cochlear implantation].

    PubMed

    Kronenberg, Jona; Migirov, Lela; Taitelbaum-Swead, Rikey; Hildesheimer, Minka

    2010-06-01

    Cochlear implant surgery became the standard of care in hearing rehabilitation of patients with severe to profound sensorineural hearing loss. This procedure may alter the lives of children and adults enabling them to integrate with the hearing population. In the past, implantation was performed only in one ear, despite the fact that binaural hearing is superior to unilateral, especially in noisy conditions. Cochlear implantation may be performed sequentially or simultaneously. The "sensitive period" of time between hearing loss and implantation and between the two implantations, when performed sequentially, significantly influences the results. Shorter time spans between implantations improve the hearing results after implantation. Hearing success after implantation is highly dependent on the rehabilitation process which includes mapping, implant adjustments and hearing training. Bilateral cochlear implantation in children is recommended as the proposed procedure in spite of the additional financial burden.

  13. [An immobilising malignant phyllodes tumour of the breast].

    PubMed

    Fritsche, E; Hug, U; Winterholer, D

    2015-04-01

    Phyllodes tumours of the breast are rare occurrences, but they can reach huge dimensions. Descriptions of tumours whereby the women are immobilised as a consequence of the size of the tumour, are hard to find in the literature. In this presentation we show a case of a woman in otherwise healthy condition with a giant phyllodes tumour of her left breast. Because of the weight of the tumour, the patient could not leave her bed for more than 6 months.

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

    PubMed

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

    2015-03-01

    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. © 2015 The authors.

  15. 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

  16. Accuracy of Various MRI Sequences in Determining the Tumour Margin in Musculoskeletal Tumours

    PubMed Central

    Putta, Tharani; Gibikote, Sridhar; Madhuri, Vrisha; Walter, Noel

    2016-01-01

    Summary Background It is imperative that bone tumour margin and extent of tumour involvement are accurately assessed pre-operatively in order for the surgeon to attain a safe surgical margin. In this study, we comprehensively assessed each of the findings that influence surgical planning, on various MRI sequences and compared them with the gold standard – pathology. Material/Methods In this prospective study including 21 patients with extremity bone tumours, margins as seen on various MRI sequences (T1, T2, STIR, DWI, post-gadolinium T1 FS) were measured and biopsies were obtained from each of these sites during the surgical resection. The resected tumour specimen and individual biopsy samples were studied to assess the true tumour margin. Margins on each of the MRI sequences were then compared with the gold standard – pathology. In addition to the intramedullary tumour margin, we also assessed the extent of soft tissue component, neurovascular bundle involvement, epiphyseal and joint involvement, and the presence or absence of skip lesions. Results T1-weighted imaging was the best sequence to measure tumour margin without resulting in clinically significant underestimation or overestimation of the tumour extent (mean difference of 0.8 mm; 95% confidence interval between −0.9 mm to 2.5 mm; inter-class correlation coefficient of 0.998). STIR and T1 FS post-gadolinium imaging grossly overestimated tumour extent by an average of 16.7 mm and 16.8 mm, respectively (P values <0.05). Post-gadolinium imaging was better to assess joint involvement while T1 and STIR were the best to assess epiphyseal involvement. Conclusions T1-weighted imaging was the best sequence to assess longitudinal intramedullary tumour extent. We suggest that osteotomy plane 1.5 cm beyond the T1 tumour margin is safe and also limits unwarranted surgical bone loss. However, this needs to be prospectively proven with a larger sample size. PMID:28058070

  17. Accuracy of Various MRI Sequences in Determining the Tumour Margin in Musculoskeletal Tumours.

    PubMed

    Putta, Tharani; Gibikote, Sridhar; Madhuri, Vrisha; Walter, Noel

    2016-01-01

    It is imperative that bone tumour margin and extent of tumour involvement are accurately assessed pre-operatively in order for the surgeon to attain a safe surgical margin. In this study, we comprehensively assessed each of the findings that influence surgical planning, on various MRI sequences and compared them with the gold standard - pathology. In this prospective study including 21 patients with extremity bone tumours, margins as seen on various MRI sequences (T1, T2, STIR, DWI, post-gadolinium T1 FS) were measured and biopsies were obtained from each of these sites during the surgical resection. The resected tumour specimen and individual biopsy samples were studied to assess the true tumour margin. Margins on each of the MRI sequences were then compared with the gold standard - pathology. In addition to the intramedullary tumour margin, we also assessed the extent of soft tissue component, neurovascular bundle involvement, epiphyseal and joint involvement, and the presence or absence of skip lesions. T1-weighted imaging was the best sequence to measure tumour margin without resulting in clinically significant underestimation or overestimation of the tumour extent (mean difference of 0.8 mm; 95% confidence interval between -0.9 mm to 2.5 mm; inter-class correlation coefficient of 0.998). STIR and T1 FS post-gadolinium imaging grossly overestimated tumour extent by an average of 16.7 mm and 16.8 mm, respectively (P values <0.05). Post-gadolinium imaging was better to assess joint involvement while T1 and STIR were the best to assess epiphyseal involvement. T1-weighted imaging was the best sequence to assess longitudinal intramedullary tumour extent. We suggest that osteotomy plane 1.5 cm beyond the T1 tumour margin is safe and also limits unwarranted surgical bone loss. However, this needs to be prospectively proven with a larger sample size.

  18. Tumour macrophages as potential targets of bisphosphonates

    PubMed Central

    2011-01-01

    Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use. Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to

  19. Gene expression profiling of liver metastases and tumour invasion in pancreatic cancer using an orthotopic SCID mouse model.

    PubMed

    Niedergethmann, M; Alves, F; Neff, J K; Heidrich, B; Aramin, N; Li, L; Pilarsky, C; Grützmann, R; Allgayer, H; Post, S; Gretz, N

    2007-11-19

    The prognosis of pancreatic adenocarcinoma is affected by early metastases and local tumour invasion beyond surgical margins. Gene expression profiling in pancreatic cancer tissue is complicated due to the high amount of RNAses being present in human tissue and that of suitable models. In order to demonstrate early metastases, the models should take into account the anatomical environment of the tumour. Using the orthotopic transplantation of pancreatic tumour cells in SCID (severe combined immunodeficiency) mice, these interactions are taken into consideration. In order to identify genes associated with local tumour invasion and metastases in ductal pancreatic cancer, we investigated a human pancreatic tumour cell line derived from an orthopic pancreatic tumour model in SCID mice. Differential gene expression was performed on the basis of microarray technique. The human MiaPaca-2 cell line was implanted orthotopically in SCID mice. Transcriptional profiling was performed on fresh frozen tissue derived from the primary tumour, the tumour invasion front and the liver metastases. Differentially expressed genes were identified using statistical analyses, and were validated with external databases and with immunohistochemistry. A total of 1066 of 14 500 genes were significantly differentially expressed. Comparing the primary tumour with the tumour invasion front, there were 614 statistically significant up- and 348 downregulated genes. Twenty-five statistically significant up- and 181 downregulated genes were identified comparing the liver metastases with the primary tumour. Eight genes (PAI-1, BNIP3l, VEGF, NSE, RGS4, HSP27, GADD45A, PTPN14) were chosen and validated in a semi-quantitative immunohistochemical analysis, which revealed a positive correlation to the array data. Overrepresentation analyses revealed a total of 66 significantly regulated pathways associated with cell proliferation, cell stress, cell communication metabolic and cytokine function. In

  20. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

    NASA Astrophysics Data System (ADS)

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.

    2016-02-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination.

  1. Clinical management of tumours in geriatric dogs and cats: systemic effects of tumours and paraneoplastic syndromes.

    PubMed

    Gorman, N T

    1990-04-21

    There are many clinical presentations of neoplastic disease in the dog and cat. Some relate to the presence of a solid mass but many relate to the systemic effect that the tumour has on the animal. This paper covers the broad categories of the systemic metabolic and haematological effects that are associated with tumours in the dog and cat.

  2. Augmented reality in bone tumour resection

    PubMed Central

    Park, Y. K.; Gupta, S.; Yoon, C.; Han, I.; Kim, H-S.; Choi, H.; Hong, J.

    2017-01-01

    Objectives We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p < 0.05, one-way analysis of variance). The probabilities of a surgeon obtaining a 10 mm surgical margin with a 3 mm tolerance were 90.2% in AR-assisted resections, and 70.7% in conventional resections. Conclusion We demonstrated that the accuracy of tumour resection was satisfactory with the help of the AR navigation system, with the tumour shown as a virtual template. In addition, this concept made the navigation system simple and available without additional cost or time. Cite this article: H. S. Cho, Y. K. Park, S. Gupta, C. Yoon, I. Han, H-S. Kim, H. Choi, J. Hong. Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143. PMID:28258117

  3. Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved

    PubMed Central

    Chen, Ji-an; Splenser, Andres; Guillory, Bobby; Luo, Jiaohua; Mendiratta, Meenal; Belinova, Blaga; Halder, Tripti; Zhang, Guohua; Li, Yi-Ping; Garcia, Jose M

    2015-01-01

    Background Cachexia and muscle atrophy are common consequences of cancer and chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake and direct effects on muscle proteolysis and protein synthesis are likely to mediate these effects, but the pathways leading to these events are not well understood. Methods We characterized molecular pathways involved in muscle atrophy induced by Lewis lung carcinoma (LLC) tumour implantation in c57/bl6 adult male mice and by administration of the chemotherapeutic agent cisplatin in mice and in C2C12 myotubes. The effects of exogenous ghrelin administration and its mechanisms of action were examined in these settings. Results Tumour implantation and cisplatin induced muscle atrophy by activating pro-inflammatory cytokines, p38-C/EBP-β, and myostatin, and by down-regulating Akt, myoD, and myogenin, leading to activation of ubiquitin-proteasome-mediated proteolysis and muscle weakness. Tumour implantation also increased mortality. In vitro, cisplatin up-regulated myostatin and atrogin-1 by activating C/EBP-β and FoxO1/3. Ghrelin prevented these changes in vivo and in vitro, significantly increasing muscle mass (P < 0.05 for LLC and P < 0.01 for cisplatin models) and grip strength (P = 0.038 for LLC and P = 0.001 for cisplatin models) and improving survival (P = 0.021 for LLC model). Conclusion Ghrelin prevents muscle atrophy by down-regulating inflammation, p38/C/EBP-β/myostatin, and activating Akt, myogenin, and myoD. These changes appear, at least in part, to target muscle cells directly. Ghrelin administration in this setting is associated with improved muscle strength and survival. PMID:26136189

  4. Desmoplastic nested spindle cell tumours and nested stromal epithelial tumours of the liver.

    PubMed

    Misra, Sunayana; Bihari, Chhagan

    2016-04-01

    Desmoplastic nested spindle cell tumour of liver (DNSTL), nested stromal-epithelial tumour (NSET) and calcifying nested stromal-epithelial tumour (CNSET) are recently described entities with similar morphology, immunohistochemistry and molecular genetics. These are rare entities with only three large case series described till date. These tumours commonly present in the paediatric age group. NSETs, in addition have been described to be associated with ectopic adrenocorticotropic hormone (ACTH) production and Cushingoid features. It is important to discuss this rare group of tumours with a low malignant potential as the most common radiological differential diagnosis is hepatoblastoma, which has a relatively poorer prognosis. Thus, a pathologist needs to keep this entity in mind, so as to offer a correct histological diagnosis.

  5. Occurrence of tumours metastatic to bones and multicentric tumours with skeletal involvement in dogs.

    PubMed

    Trost, M E; Inkelmann, M A; Galiza, G J N; Silva, T M; Kommers, G D

    2014-01-01

    The skeletons of 110 dogs with malignant tumours of different origins were examined by necropsy examination over a 3-year period to identify bone metastases. Twenty-one cases of metastatic or multicentric tumours with bone involvement were recorded. In general, more female dogs presented with bony metastases; however, when the dogs with mammary tumours were omitted, the gender distribution of the cases was approximately equivalent. The mammary gland was the primary site of most of the metastatic bone lesions, followed by the musculoskeletal system and the respiratory system. The majority (77%) of metastases were grossly visible and present in multiple bones. However, in 23% of the cases, the metastases could be diagnosed only at the microscopical level. The vertebrae and the humerus were the most frequently affected bones regardless of the primary site and the histogenesis of the tumours. The results of this study revealed a high prevalence of bone metastases and/or bone involvement in dogs with multicentric tumours.

  6. CD34 + tumours of the orbit including solitary fibrous tumours: a six-case series.

    PubMed

    Jung, Su Kyung; Paik, Ji Sun; Park, Gyeong Sin; Yang, Suk-Woo

    2017-04-27

    To report six cases of CD34+ fibroblastic mesenchymal tumours, which are uncommon neoplasms in the orbit. Six patients presenting with proptosis and palpable mass who were later diagnosed with fibrous solitary tumours, fibrous histocytoma or haemangiopericytoma in the orbit were included. All patients received radiologic examinations and surgical excision for histopathology and immunohistochemistry examinations. Five patients had no recurrence after a minimum follow-up of 12 months. One patient (case 6) experienced recurrence twice, and had debulking surgeries each time. At present, the patient still has remnant tumour in the orbit, but no growth has been detected during the past two years. The tumour size will be closely monitored. Even though fibroblastic tumours are rarely found in the orbit, they can present as a palpable mass with proptosis. Complete surgical excision is important for long-term prognosis, and immunohistochemical study is helpful for confirming pathologic diagnosis.

  7. Loss of the tumour suppressor gene AIP mediates the browning of human brown fat tumours.

    PubMed

    Magnusson, Linda; Hansen, Nils; Saba, Karim H; Nilsson, Jenny; Fioretos, Thoas; Rissler, Pehr; Nord, Karolin H

    2017-10-01

    Human brown fat tumours (hibernomas) show concomitant loss of the tumour suppressor genes MEN1 and AIP. We hypothesized that the brown fat phenotype is attributable to these mutations. Accordingly, in this study, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumours, loss of MEN1 was found both in white (one of 51 lipomas) and in brown fat tumours. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology. We conclude that this white-to-brown phenotype switch in brown fat tumours is mediated by the loss of AIP. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  8. Clinical relevance associated to the analysis of circulating tumour cells in patients with solid tumours.

    PubMed

    Serrano Fernádez, María José; Alvarez Merino, Juan Carlos; Martínez Zubiaurre, Iñigo; Fernández García, Ana; Sánchez Rovira, Pedro; Lorente Acosta, José Antonio

    2009-10-01

    The distant growth of tumour cells escaping from primary tumours, a process termed metastasis, represents the leading cause of death among patients affected by malignant neoplasias from breast and colon. During the metastasis process, cancer cells liberated from primary tumour tissue, also termed circulating tumour cells (CTCs), travel through the circulatory and/or lymphatic systems to reach distant organs. The early detection and the genotypic and phenotypic characterisation of such CTCs could represent a powerful diagnostic tool of the disease, and could also be considered an important predictive and prognostic marker of disease progression and treatment response. In this article we discuss the potential relevance in the clinic of monitoring CTCs from patients suffering from solid epithelial tumours, with emphasis on the impact of such analyses as a predictive marker for treatment response.

  9. Vascular tumours in infants. Part I: benign vascular tumours other than infantile haemangioma.

    PubMed

    Hoeger, P H; Colmenero, I

    2014-09-01

    Vascular anomalies can be subdivided into vascular tumours and vascular malformations (VMs). While most VMs are present at birth and do not exhibit significant postnatal growth, vascular tumours are characterized by their dynamics of growth and (sometimes) spontaneous regression. This review focuses on benign vascular tumours other than infantile haemangiomas (IHs), namely pyogenic granuloma, eruptive pseudoangiomatosis, glomangioma, rapidly involuting and noninvoluting congenital haemangioma, verrucous haemangioma and spindle cell haemangioma. While some of them bear clinical resemblance to IH, they can be separated by age of appearance, growth characteristics and/or negative staining for glucose transporter 1. Separation of these tumours from IH is necessary because their outcome and therapeutic options are different. Semimalignant and malignant vascular tumours will be addressed in a separate review.

  10. Naturally occurring tumours in the basal metazoan Hydra.

    PubMed

    Domazet-Lošo, Tomislav; Klimovich, Alexander; Anokhin, Boris; Anton-Erxleben, Friederike; Hamm, Mailin J; Lange, Christina; Bosch, Thomas C G

    2014-06-24

    The molecular nature of tumours is well studied in vertebrates, although their evolutionary origin remains unknown. In particular, there is no evidence for naturally occurring tumours in pre-bilaterian animals, such as sponges and cnidarians. This is somewhat surprising given that recent computational studies have predicted that most metazoans might be prone to develop tumours. Here we provide first evidence for naturally occurring tumours in two species of Hydra. Histological, cellular and molecular data reveal that these tumours are transplantable and might originate by differentiation arrest of female gametes. Growth of tumour cells is independent from the cellular environment. Tumour-bearing polyps have significantly reduced fitness. In addition, Hydra tumours show a greatly altered transcriptome that mimics expression shifts in vertebrate cancers. Therefore, this study shows that spontaneous tumours have deep evolutionary roots and that early branching animals may be informative in revealing the fundamental mechanisms of tumorigenesis.

  11. Expression and significance of PTEN in canine mammary gland tumours.

    PubMed

    Qiu, Changwei; Lin, Degui; Wang, Jinqiu; Wang, Lei

    2008-10-01

    To explore the expression and clinical importance of the anti-oncogene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in canine mammary gland tumours, PTEN expression was compared in 50 cases of canine mammary tumour and four examples of normal mammary tissue using real-time quantitative PCR. PTEN expression was similar in benign mammary tumours and normal mammary tissues (P>0.05), but was lower in malignant tumours than in normal mammary tissues or benign mammary tumours (P<0.001). PTEN expression was also low in the lymph node metastases of malignant mammary tumours. The expression profile of PTEN in malignant mammary tumours compared to those without lymph node metastasis varied significantly. Low-level PETN expression might play an important role in carcinogenesis and the progression of canine mammary tumours, and PTEN protein detection might be useful in evaluating tumour development and prognosis.

  12. Biofilm formation by Salmonella enterica serovar Typhimurium colonizing solid tumours.

    PubMed

    Crull, Katja; Rohde, Manfred; Westphal, Kathrin; Loessner, Holger; Wolf, Kathrin; Felipe-López, Alfonso; Hensel, Michael; Weiss, Siegfried

    2011-08-01

    Systemic administration of Salmonella enterica serovar Typhimurium to tumour bearing mice results in preferential colonization of the tumours and retardation of tumour growth. Although the bacteria are able to invade the tumour cells in vitro, in tumours they were never detected intracellularly. Ultrastructural analysis of Salmonella-colonized tumours revealed that the bacteria had formed biofilms. Interestingly, depletion of neutrophilic granulocytes drastically reduced biofilm formation. Obviously, bacteria form biofilms in response to the immune reactions of the host. Importantly, we tested Salmonella mutants that were no longer able to form biofilms by deleting central regulators of biofilm formation. Such bacteria could be observed intracellularly in immune cells of the host or in tumour cells. Thus, tumour colonizing S. typhimurium might form biofilms as protection against phagocytosis. Since other bacteria are behaving similarly, solid murine tumours might represent a unique model to study biofilm formation in vivo. © 2011 Blackwell Publishing Ltd.

  13. Norplant implants.

    PubMed

    Henley, E

    1993-06-01

    This letter to the editor is in response to 3 articles on the use of the Norplant implant contraceptive in The Indian Health Service (IHS) Provider. Norplant and the FDA-approved Depo-Provera now expand contraceptive options for women. All IHS and 638 sites might be able to offer both options. Several of the authors expressed concern regarding decreased Norplant effectiveness in heavier patients. Norplant is still more effective than any other currently available reversible contraceptive in the US at all weights. Many experts feel the current silastic capsule provides adequate hormone levels even in heavier women. The Crow Service Unit has initiated their Norplant program, although the Wyeth consent form seems unnecessarily extensive. The Albuquerque Service Unit consent form simply describes the procedure and confirms that patients have read and understand the fact sheet. The theoretical risk of thromboembolism is vastly outweighed by the potential benefit of reliable contraception in high risk alcoholic women, except perhaps in women with severe liver disease. While Norplant is expensive, programs need to consider the actual cost of a pregnancy, potential complications, and the financial and social costs of unintended pregnancy. For those in difficult straits, the manufacturer has set up a foundation for obtaining Norplant free of charge. Depo-Provera comes in a 150 mg dose vial that is given every 3 months. The mean time to ovulation is 4.5 months from the last dose. The adverse reaction spectrum is similar to Norplant as they are both progesterone-related agents. Providers and clinics should reduce barriers to family planning by giving out more pill packs at a time; letting adolescents who wish to delay their first pelvic exam have 3 months of pills without an exam; making condoms available in exam rooms rather than through pharmacy prescriptions; and increasing patient accessibility to the morning-after pill.

  14. SIRT2: tumour suppressor or tumour promoter in operable breast cancer?

    PubMed

    McGlynn, Liane M; Zino, Samer; MacDonald, Alasdair I; Curle, Jennifer; Reilly, Justice E; Mohammed, Zahra M A; McMillan, Donald C; Mallon, Elizabeth; Payne, Anthony P; Edwards, Joanne; Shiels, Paul G

    2014-01-01

    Sirtuins comprise a family of genes involved in cellular stress, survival and damage responses. They have been implicated in a range of diseases including cancer, with most information pertaining to their function in tumourigenesis being derived from in vitro studies, or model organisms. Their putative roles as tumour suppressors or tumour promoters remain to be validated in vivo. Little is known about their role in breast tumourigenesis. We sought to evaluate the seven sirtuin family members (SIRT1-7) in a human breast cancer cohort, in relation to clinico-pathological features and outcome of the disease. Immunohistochemical analysis of SIRT1-7 protein levels was undertaken in 392 oestrogen receptor (ER+ve) and 153 ER-ve breast tumour samples. SIRT1-7 transcriptional levels were assessed in normal (n=25), non-malignant (n=73) and malignant (n=70) breast tissue using Relative Quantitative Real Time PCR. Statistical analyses determined if SIRT1-7 transcription or protein expression was associated with clinical parameters or outcome. In ER-ve tumours, high protein levels of nuclear SIRT2 were associated with reduced time to recurrence and disease-specific death. This association was only observed in Grade 3 tumours. In the ER+ve cohort, high SIRT2 nuclear levels were associated with shorter disease-free survival and time to recurrence whilst on Tamoxifen, in patients with Grade 3 tumours. Conversely, in Grade 2 tumours, high SIRT2 levels were associated with increased time to recurrence. Our data suggest that SIRT2 is the sirtuin predominantly involved in breast tumourigenesis and prognosis. It indicates that SIRT2 acts as a tumour suppressor or tumour promoter dependent upon breast tumour grade. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Phylogenetic Quantification of Intra-tumour Heterogeneity

    PubMed Central

    Schwarz, Roland F.; Trinh, Anne; Sipos, Botond; Brenton, James D.; Goldman, Nick; Markowetz, Florian

    2014-01-01

    Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity. Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data. PMID:24743184

  16. Targeting the tumour microenvironment in ovarian cancer.

    PubMed

    Hansen, Jean M; Coleman, Robert L; Sood, Anil K

    2016-03-01

    The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Neuroendocrine tumours: cracking the epigenetic code.

    PubMed

    Karpathakis, A; Dibra, H; Thirlwell, C

    2013-06-01

    The field of epigenetics has evolved rapidly over recent years providing insight into the tumorigenesis of many solid and haematological malignancies. Determination of epigenetic modifications in neuroendocrine tumour (NET) development is imperative if we are to improve our understanding of the biology of this heterogenous group of tumours. Epigenetic marks such as DNA methylation at RASSF1A are frequent findings in NETs of all origins and may be associated with worse prognosis. MicroRNA signatures and histone modifications have been identified which can differentiate subtypes of NET and distinguish NET from adenocarcinoma in cases of diagnostic uncertainty. Historically, candidate gene-driven approaches have yielded limited insight into the epigenetics of NET. Recent progress has been facilitated by development of high-throughput tools including second-generation sequencing and arrays for analysis of the 'epigenome' of tumour and normal tissue, permitting unbiased approaches such as exome sequencing that identified mutations of chromatin-remodelling genes ATRX/DAXX in 44% of pancreatic NETs. Epigenetic changes are reversible and therefore represent an attractive therapeutic target; to date, clinical outcomes of epigenetic therapies in solid tumours have been disappointing; however, in vitro studies on NETs are promising and further clinical trials are required to determine utility of this class of novel agents. In this review, we perform a comprehensive evaluation of epigenetic changes found in NETs to date, including rare NETs such as phaeochromocytoma and adrenocortical tumours. We suggest priorities for future research and discuss potential clinical applications and novel therapies.

  18. Imaging tumours of the ampulla of Vater.

    PubMed

    Zbar, Andrew P; Maor, Yaakov; Czerniak, Abraham

    2012-12-01

    Although comparatively rare, ampullary tumours tend to be more readily curable than periampullary lesions and pancreatic carcinomas, consequent upon an earlier presentation, a lower likelihood of involved lymph nodes or vascular infiltration and a less aggressive histology. Recently, selected early cases have been able to resected endoscopically making accurate preoperative tumour (T) staging critical in such decision making. The most commonly available imaging methods are endoscopic ultrasound (EUS) and CT scanning where in the former case there is variable accuracy for larger (T2/T3) ampullary tumours particularly where the patient has undergone preoperative common bile duct stenting. CT scanning has consistent shown inferior T staging of ampullary tumours when compared with EUS, although it provides information concerning visceral and nodal metastatic disease. Transpapillary intraductal ultrasound (where available) has shown high accuracy for early T1 tumours potentially suitable for endoscopic or local ampullary excision with the added advantage that it may be conducted without preliminary sphincterotomy. Recently, our group has been using intraoperative transduodenal ultrasound which assists surgical decision making concerning local excision or radical pancreaticoduodenal resection. Very recent images using 3-dimensional endoduodenal ultrasound has provided exquisite images of the ampulla and remain to be validated in ampullary neoplasms.

  19. The diagnosis of soft tissue tumours.

    PubMed Central

    Serpell, J. W.; Fish, S. H.; Fisher, C.; Thomas, J. M.

    1992-01-01

    We prospectively analysed methods of diagnosis in 118 patients referred for definitive treatment with documented or presumed soft tissue sarcoma (STS). Of 65 patients with primary STS, 54 were biopsied before referral. Of these, 5 (9%) were biopsied by Tru-cut biopsy, 17 (32%) by incisional biopsy and 32 (59%) by excisional biopsy. The remaining 11 patients with primary STS, referred without biopsy, were all diagnosed by Tru-cut biopsy. An additional eight patients suspected of having STS were referred without biopsy and were found to have malignant tumours other than STS involving soft tissue by Tru-cut biopsy. Nineteen patients were proved to have benign soft tissue tumours; in 13 presumed to have STS, the diagnosis was unknown at referral. In four of these, biopsy was inappropriate. Of nine submitted to Tru-cut biopsy, an unequivocal diagnosis was made in 5 (56%) and incisional biopsy was required in the other four. Therefore, paradoxically, benign soft tissue tumours may be more difficult to diagnose with Tru-cut biopsy than malignant tumours. This study confirms the high degree of accuracy of Tru-cut biopsy in diagnosing malignant soft tissue tumours and highlights the disadvantages of open biopsy techniques. PMID:1416683

  20. [Tumours of the upper cervical spine].

    PubMed

    Hernández García, Borja Jesús; Isla Guerrero, Alberto; Castaño, Ana; Alvarez Ruiz, Fernando; Gómez de la Riva, Alvaro

    2013-01-01

    Vertebral tumours arising in the upper cervical spine are rare. We present our experience in managing these neoplasms. We retrospectively reviewed the case histories of patients treated at our institution between January 2000 and June 2011. There were 9 patients with tumours in C1-C2-C3: 2metastases, 3chordomas, 2plasmocytomas, 1chondrosarcoma and 1osteochondroma. All patients complained of neck pain at the time of diagnosis. Three patients underwent an anterior and posterior approach, 3 an exclusively posterior approach and 3 an exclusively anterior surgical approach. Tumour resection was intralesional in 7 cases. Chemo-radiotherapy was used as adjuvant therapy in patients with malignant tumours. Vertebral tumours in the upper cervical spine are usually malignant. Achieving en bloc resection is particularly challenging and is technically unfeasible in many cases. This worsens the prognosis and makes adjuvant treatment very important. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  1. [New TNM classification of malignant lung tumours].

    PubMed

    Wohlschläger, J; Wittekind, C; Theegarten, D

    2010-09-01

    The staging system for lung tumours is now recommended for the classification of both non-small-cell and small-cell lung cancer as well as for carcinoid tumours of the lung. The T classifications have been redefined: T1 has been subclassified as T1a (≤ 2 cm in size) and T1b (> 2-3 cm in size). T2 has been subclassified as T2a (> 3-5 cm in size) and T2b (> 5-7 cm in size). T2 (> 7 cm in size) has been reclassified as T3. Multiple tumour nodules in the same lobe have been reclassified from T4 to T3. Multiple tumour nodules in the same lung but a different lobe have been reclassified from M1 to T4. No changes have been made in the N classification. The M classification has been redefined: M1 has been subdivided into M1a and M1b. Malignant pleural and pericardial effusions have been reclassified from T4 to M1a. Separate tumour nodules in the contralateral lung have been reclassified from T4 to M1a. M1b designates distant metastasis.

  2. Constitutional ring chromosomes and tumour suppressor genes.

    PubMed Central

    Tommerup, N; Lothe, R

    1992-01-01

    The types of malignancy reported in carriers of constitutional ring chromosomes r(11), r(13), and r(22) are concordant with the chromosomal assignment of tumour suppressor loci associated with Wilms' tumour, retinoblastoma, and meningioma. It is suggested that the somatic instability of ring chromosomes may play a role in this association and that constitutional ring chromosomes may be a source for mapping of tumour suppressor loci with the potential for covering most or all of the human genome. The hypothesis predicts the presence of a locus on chromosome 10 associated with follicular carcinoma of the thyroid, in line with previous cytogenetic findings of rearrangements involving chromosome 10 in thyroid tumours, and a locus on chromosome 22 associated with testicular cancer. Development of neurofibromatoses (NF) that do not fulfil the clinical criteria of neurofibromatosis type 2 (NF2) in carriers with r(22) suggests either the presence of an additional NF locus on chromosome 22 or that ring chromosome mediated predisposition to somatic mutation of a specific tumour suppressor may be associated with atypical development of features usually associated with germline mutations. PMID:1336057

  3. Objective tumour heterogeneity determination in gliomas

    NASA Astrophysics Data System (ADS)

    Simon, Dirk; Klein, Jan; Rexilius, Jan; Stieltjes, Bram

    2009-02-01

    Diffusion weighted imaging (DWI) derived apparent diffusion coefficient (ADC) values are known to correlate inversely to tumour cellularity in brain tumours. The average ADC value increases after successful chemotherapy, radiotherapy or a combination of both and can be therewith used as a surrogate marker for treatment response. Moreover, high and low malignant areas can be distinguished. The main purpose of our project was to develop a software platform that enables the automated delineation and ADC quantification of different tumour sections in a fast, objective, user independent manner. Moreover, the software platform allows for an analysis of the probability density of the ADC in high and low malignant areas in ROIs drawn on conventional imaging to create a ground truth. We tested an Expectation Maximization algorithm with a Gaussian mixture model to objectively determine tumour heterogeneity in gliomas because of yielding Gaussian distributions in the different areas. Furthermore, the algorithm was initialized by seed points in the areas of the gross tumour volume and the data indicated that an automatic initialization should be possible. Thus automated clustering of high and low malignant areas and subsequent ADC determination within these areas is possible yielding reproducible ADC measurements within heterogeneous gliomas.

  4. Mast cells, angiogenesis, and tumour growth.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2012-01-01

    Accumulation of mast cells (MCs) in tumours was described by Ehrlich in his doctoral thesis. Since this early account, ample evidence has been provided highlighting participation of MCs to the inflammatory reaction that occurs in many clinical and experimental tumour settings. MCs are bone marrow-derived tissue-homing leukocytes that are endowed with a panoply of releasable mediators and surface receptors. These cells actively take part to innate and acquired immune reactions as well as to a series of fundamental functions such as angiogenesis, tissue repair, and tissue remodelling. The involvement of MCs in tumour development is debated. Although some evidence suggests that MCs can promote tumourigenesis and tumour progression, there are some clinical sets as well as experimental tumour models in which MCs seem to have functions that favour the host. One of the major issues linking MCs to cancer is the ability of these cells to release potent pro-angiogenic factors. This review will focus on the most recent acquisitions about this intriguing field of research. This article is part of a Special Issue entitled: Mast cells in inflammation. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Approaches to paraspinal tumours - a technical note.

    PubMed

    Dhar, Arjun; Pawar, Sumeet; Prasad, Apurva; Ramani, P S

    2017-03-23

    Neurogenic tumours of the paraspinal space can occur in all age groups. It is common in adult population and relatively rare in elderly group. Usually they are benign, but in children, arising from the autonomic system, tends to be malignant in nature. Usually in adults, they arise from peripheral nerve sheath and are labelled as schwannomas. For a given tumour, determination of a correct surgical approach is mandatory to achieve a successful surgical outcome. Several factors like tumour size, histology, involvement of the bony spinal canal, etc. are some of the deciding factors for a correct surgical approach. Since many such tumours are benign, total excision is possible with a correct surgical approach. If the tumour involves the integrity of the spine then additionally a stabilization procedure may have to be carried out. Unfortunately, there are still no guidelines regarding the choice of surgical approach for the excision of such tumors. Presented here is a series of five patients managed by us over a period of 10 years. Four patients were adults and one female child was three years old. Four patients were operated upon successfully and the fifth one is waiting for surgery.

  6. Giant malignant phyllodes tumour of breast.

    PubMed

    Krishnamoorthy, Ramakrishnan; Savasere, Thejas; Prabhuswamy, Vinod Kumar; Babu, Rajashekhara; Shivaswamy, Sadashivaiah

    2014-01-01

    The term phyllodes tumour includes lesions ranging from completely benign tumours to malignant sarcomas. Clinically phyllodes tumours are smooth, rounded, and usually painless multinodular lesions indistinguishable from fibroadenomas. Percentage of phyllodes tumour classified as malignant ranges from 23% to 50%. We report a case of second largest phyllodes tumour in a 35-year-old lady who presented with swelling of right breast since 6 months, initially small in size, that progressed gradually to present size. Examination revealed mass in the right breast measuring 36×32 cms with lobulated firm surface and weighing 10 kgs. Fine needle aspiration cytology was reported as borderline phyllodes; however core biopsy examination showed biphasic neoplasm with malignant stromal component. Simple mastectomy was done and specimen was sent for histopathological examination which confirmed the core biopsy report. Postoperatively the patient received chemotherapy and radiotherapy. The patient is on follow-up for a year and has not shown any evidence of metastasis or recurrence.

  7. [Pax-2 antigen expression in kidney tumours].

    PubMed

    Vjestica, Jelena M; Marković-Lipkovski, Jasmina; Tulić, Cane D; Djokić, Milan R; Segar, Bojan S; Cirović, Sanja L; Stojanović, Martina M; Vuksanović, Aleksandar M

    2011-01-01

    Pax-2 transcriptional factor is expressed during kidney development and could re-express in renal tumors. The aim of this study was to examine Pax-2 expression in different types of renal cell carcinoma (RCC) in order to see whether it is good immunohistochemical marker. We analyzed 48 different renal tumours stained with Pax-2 antibody. Pax-2 positive reaction was noticed in nucleus or cytoplasm. Expression of this antigen in tumours tissue was correlated with tumour stage and nuc-lear grade. Pax-2 expression between different histological RCC types was analyzed by chi2 test and Fishers test for two in-depended samples. Pax-2 is expressed by a high percentage of re-nal tumors regardless of histologic type. Significant diffe-rence of Pax-2 expression between oncocytomas and chromofobe RCC was found. Nuclear expression of Pax-2 is useful diagnostic kidney tumour marker. Pax-2 showed stronger expression in lower malignancy kidney tumours and in oncocytomas, than in high grade RCC like in those with sarcomatoid differentiation

  8. Spontaneous transformation of human granulosa cell tumours into an aggressive phenotype: a metastasis model cell line

    PubMed Central

    Imai, Misa; Muraki, Miho; Takamatsu, Kiyoshi; Saito, Hidekazu; Seiki, Motoharu; Takahashi, Yuji

    2008-01-01

    Background Granulosa cell tumours (GCTs) are frequently seen in menopausal women and are relatively indolent. Although the physiological properties of normal granulosa cells have been studied extensively, little is known about the molecular mechanism of GCT progression. Here, we characterise the unique behavioural properties of a granulosa tumour cell line, KGN cells, for the molecular analysis of GCT progression. Methods Population doubling was carried out to examine the proliferation capacity of KGN cells. Moreover, the invasive capacity of these cells was determined using the in vitro invasion assay. The expression level of tumour markers in KGN cells at different passages was then determined by Western blot analysis. Finally, the growth and metastasis of KGN cells injected subcutaneously (s.c.) into nude mice was observed 3 months after injection. Results During in vitro culture, the advanced passage KGN cells grew 2-fold faster than the early passage cells, as determined by the population doubling assay. Moreover, we found that the advanced passage cells were 2-fold more invasive than the early passage cells. The expression pattern of tumour markers, such as p53, osteopontin, BAX and BAG-1, supported the notion that with passage, KGN cells became more aggressive. Strikingly, KGN cells at both early and advanced passages metastasized to the bowel when injected s.c. into nude mice. In addition, more tumour nodules were formed when the advanced passage cells were implanted. Conclusion KGN cells cultured in vitro acquire an aggressive phenotype, which was confirmed by the analysis of cellular activities and the expression of biomarkers. Interestingly, KGN cells injected s.c. are metastatic with nodule formation occurring mostly in the bowel. Thus, this cell line is a good model for analysing GCT progression and the mechanism of metastasis in vivo. PMID:18980698

  9. The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation.

    PubMed Central

    Brizel, D. M.; Lin, S.; Johnson, J. L.; Brooks, J.; Dewhirst, M. W.; Piantadosi, C. A.

    1995-01-01

    Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the amount of dissolved oxygen in the plasma. That this actually occurs has not been verified experimentally. This study was performed to explore changes in tumour oxygenation induced by treatment with normobaric and hyperbaric oxygen and carbogen. R3230Ac mammary adenocarcinomas were implanted into Fisher 344 rats. Arterial blood gases, blood pressure and heart rate were monitored. Tumour oxygenation was measured polarographically in five sets of animals. They received either normobaric 100% oxygen, hyperbaric (3 atmospheres; atm) 100% oxygen, normobaric carbogen or hyperbaric (3 atm) carbogen (HBC) +/- bretylium. HBO reduced the mean level of low pO2 values (< 5 mmHg) from 0.49 to 0.07 (P = 0.0003) and increased the average median pO2 from 8 mmHg to 55 mmHg (P = 0.001). HBC reduced the level of low pO2 values from 0.82 to 0.51 (P = 0.002) an increased median pO2 from 2 mmHg to 6 mmHg (P = 0.05). Normobaric oxygen and carbogen did not change tumour oxygenation significantly. Sympathetic blockade with bretylium before HBC exposure improved oxygenation significantly more than HBC alone (low pO2 0.55-0.17, median pO2 4-17 mmHg). HBO and hyperbaric carbogen improved tumour oxygenation in this model, while normobaric oxygen or carbogen had no effect. Sympathetic-mediated vasoconstriction during hyperbaric carbogen caused it to be less effective than HBO. This mechanism also appeared to operate during normobaric carbogen breathing. PMID:7577456

  10. The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation.

    PubMed

    Brizel, D M; Lin, S; Johnson, J L; Brooks, J; Dewhirst, M W; Piantadosi, C A

    1995-11-01

    Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the amount of dissolved oxygen in the plasma. That this actually occurs has not been verified experimentally. This study was performed to explore changes in tumour oxygenation induced by treatment with normobaric and hyperbaric oxygen and carbogen. R3230Ac mammary adenocarcinomas were implanted into Fisher 344 rats. Arterial blood gases, blood pressure and heart rate were monitored. Tumour oxygenation was measured polarographically in five sets of animals. They received either normobaric 100% oxygen, hyperbaric (3 atmospheres; atm) 100% oxygen, normobaric carbogen or hyperbaric (3 atm) carbogen (HBC) +/- bretylium. HBO reduced the mean level of low pO2 values (< 5 mmHg) from 0.49 to 0.07 (P = 0.0003) and increased the average median pO2 from 8 mmHg to 55 mmHg (P = 0.001). HBC reduced the level of low pO2 values from 0.82 to 0.51 (P = 0.002) an increased median pO2 from 2 mmHg to 6 mmHg (P = 0.05). Normobaric oxygen and carbogen did not change tumour oxygenation significantly. Sympathetic blockade with bretylium before HBC exposure improved oxygenation significantly more than HBC alone (low pO2 0.55-0.17, median pO2 4-17 mmHg). HBO and hyperbaric carbogen improved tumour oxygenation in this model, while normobaric oxygen or carbogen had no effect. Sympathetic-mediated vasoconstriction during hyperbaric carbogen caused it to be less effective than HBO. This mechanism also appeared to operate during normobaric carbogen breathing.

  11. ET-39REPEATED PHARMACOLOGICAL DOSES OF ASCORBATE PROTECTS TUMOURS FROM RADIATION DAMAGE IN AN INTRACRANIAL MOUSE GLIOMA MODEL

    PubMed Central

    McConnell, Melanie; Grasso, Carole; Fabre, Marie-Sophie; Collis, Sarah; Castro, Leticia; Schleich, Nanette; Herst, Patries

    2014-01-01

    High dose ascorbate is used as an anti-cancer treatment by complementary and alternative medicine. In the acidic, metal-rich tumour environment ascorbate acts as a pro-oxidant, generating free radicals and DNA damage, similar to ionising radiation. We showed that addition of high-dose ascorbate to radiation blocked repair of radiation-induced DNA damage in primary GBM cell lines, effectively radio-sensitising. We examined the effect of ascorbate and radiation on the murine glioma GL261 in vitro, and combined with intra-peritoneal ascorbate in an intra-cranial GL261 model. As previously seen, high dose ascorbate radio-sensitized GL261 cells in a clonogenicity assay. Tumour-bearing mice were treated with: 4.5Gy to the brain 8 days post-implantation; repeated high-dose ascorbate from day 8-45; both treatments; or no treatment. While radiation increased survival, intraperitoneal ascorbate alone had no effect. In contrast with in vitro data, tumour-bearing mice treated with radiation and daily ascorbate had poorer survival than those treated with radiation alone. Histological analysis of the tumours showed less necrosis and bleeding within tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. While the mechanism of protection is not yet defined, this finding might have important clinical implications for combining high-dose ascorbate with radiation therapy.

  12. Flaxseed cotyledon fraction reduces tumour growth and sensitises tamoxifen treatment of human breast cancer xenograft (MCF-7) in athymic mice.

    PubMed

    Chen, Jianmin; Saggar, Jasdeep K; Corey, Paul; Thompson, Lilian U

    2011-02-01

    Dietary flaxseed (FS) inhibited the growth of human breast tumours and enhanced the effectiveness of tamoxifen (TAM) in athymic mice with low oestradiol (E2) levels. The present study determined whether the n-3 fatty acid-rich cotyledon fraction of FS (FC), alone or in combination with TAM, has a similar effect and thus can substitute for FS. In a 2 × 2 factorial design, ovariectomised mice with established oestrogen receptor (ER)-positive breast tumours (MCF-7) were treated as follows: groups 1 and 2 were fed the basal diet (BD, control) and FC diet (82 g FC/kg), respectively. Groups 3 and 4 with TAM implants (5 mg) were fed the BD and FC diet, respectively. At 8 weeks post-treatment, mice were euthanised, and tumours were analysed by immunohistochemistry and real-time PCR. BD, FC and FC/TAM groups significantly decreased tumour area, but the TAM group did not. Tumour regression in the FC/TAM group was greater compared to the TAM group. FC lowered cell proliferation but had no effect on apoptosis; the opposite was observed with TAM. FC suppressed mRNA expressions of pS2 and insulin-like growth factor 1 receptor (IGF-1R) and protein expressions of ERα, phosphospecific ERα, human epidermal growth factor receptor 2 (HER2), phosphospecific HER2 (pHER2) and amplified in breast 1 (AIB1), while TAM up-regulated mRNA expressions of Bcl2, progesterone receptor and IGF-1R and protein expression of pHER2, and down-regulated ERβ mRNA. FC modulated the effect of TAM on tumour growth biomarkers. In conclusion, FC reduced the growth of ER+ human breast tumours at low circulating E2, alone and combined with TAM, in part through modulation of ER- and growth factor-mediated signalling pathways; it may substitute for FS in increasing the effectiveness of TAM.

  13. Thalidomide increases both intra-tumoural tumour necrosis factor-α production and anti-tumour activity in response to 5,6-dimethylxanthenone-4-acetic acid

    PubMed Central

    Cao, Z; Joseph, W R; Browne, W L; Mountjoy, K G; Palmer, B D; Baguley, B C; Ching, L-M

    1999-01-01

    5,6-Dimethylxanthenone-4-acetic acid (DMXAA), synthesized in this laboratory and currently in phase I clinical trial, is a low molecular weight inducer of tumour necrosis factor-α (TNF-α). Administration of DMXAA to mice with established transplantable tumours elicits rapid vascular collapse selectively in the tumour, followed by extensive haemorrhagic necrosis mediated primarily through the production of TNF-α. In this report we have investigated the synthesis of TNF-α mRNA in hepatic, splenic and tumour tissue. Co-administration of thalidomide with DMXAA increased anti-tumour activity and increased intra-tumoural TNF-α production approximately tenfold over that obtained with DMXAA alone. Thalidomide increased splenic TNF-α production slightly but significantly decreased serum and hepatic levels of TNF-α induced with DMXAA. Lipopolysaccharide (LPS) induced 300-fold higher serum TNF-α than did DMXAA at the maximum tolerated dose, but induced similar amounts of TNF-α in spleen, liver and tumour. Splenic TNF-α activity induced with LPS was slightly increased with thalidomide, but serum and liver TNF-α levels were suppressed. Thalidomide did not increase intra-tumoural TNF-α production induced with LPS, in sharp contrast to that obtained with DMXAA. While thalidomide improved the anti-tumour response to DMXAA, it had no effect on the anti-tumour action of LPS that did not induce a significant growth delay or cures against the Colon 38 tumour. The increase in the anti-tumour action by thalidomide in combination with DMXAA corresponded to an increase in intra-tumoural TNF-α production. Co-administration of thalidomide may represent a novel approach to improving selective intra-tumoural TNF-α production and anti-tumour efficacy of DMXAA. © 1999 Cancer Research Campaign PMID:10360649

  14. [Biomaterials in cochlear implants].

    PubMed

    Stöver, T; Lenarz, T

    2009-05-01

    Cochlear implants (CI) represent the "gold standard" for the treatment of congenitally deaf children and postlingually deafened adults. Thus, cochlear implantation is a success story of new bionic prosthesis development. Owing to routine application of cochlear implants in adults but also in very young children (below the age of one), high demands are placed on the implants. This is especially true for biocompatibility aspects of surface materials of implant parts which are in contact with the human body. In addition, there are various mechanical requirements which certain components of the implants must fulfil, such as flexibility of the electrode array and mechanical resistance of the implant housing. Due to the close contact of the implant to the middle ear mucosa and because the electrode array is positioned in the perilymphatic space via cochleostomy, there is a potential risk of bacterial transferral along the electrode array into the cochlea. Various requirements that have to be fulfilled by cochlear implants, such as biocompatibility, electrode micromechanics, and although a very high level of technical standards has been carried out there is still demand for the improvement of implants as well as of the materials used for manufacturing, ultimately leading to increased implant performance. General considerations of material aspects related to cochlear implants as well as potential future perspectives of implant development will be discussed.

  15. [Human tumour banks: imperative in medicine].

    PubMed

    Carvalho, Lina; Bernardo, M Teresa; Tavares, Mariana; Cotovio, Patrícia; Mação, Patrícia; Oliveira, Carlos

    2007-01-01

    A tumour bank is a consequence of the modern medicine to follow the knowledge of bio-pathology of pre-neoplastic and neoplastic diseases in order to define diagnostic criteria and accurate therapy. It can be an independent unit but it should depend on a real or virtual net in the country or in connection between different states. The informed agreement of the patient and law are integrally followed according with each country legislation and medical ethics is never overtaken for the accomplishment of diagnosis in the departments of pathology. A tumour bank works in the department of pathology, depends on trained technicians and pathologists and requires specific equipment for the different types of re-collecting, after dealing with confidentiality and law determinations. There are already some tumour bank nets in Europe (Spain, Croatia, Holland, UK, Germany) and Portugal is starting now its way.

  16. Laparoscopic resection of duodenal gastrointestinal stromal tumour

    PubMed Central

    Zioni, Tammy; Dizengof, Vitaliy; Kirshtein, Boris

    2017-01-01

    Only a few studies have revealed using laparoscopic technique with limited resection of gastrointestinal stromal tumour (GIST) of the duodenum. A 68-year-old man was admitted to the hospital due to upper gastrointestinal (GI) bleeding. Evaluation revealed an ulcerated, bleeding GI tumour in the second part of the duodenum. After control of bleeding during gastroduodenoscopy, he underwent a laparoscopic wedge resection of the area. During 1.5 years of follow-up, the patient is disease free, eats drinks well, and has regained weight. Surgical resection of duodenal GIST with free margins is the main treatment of this tumour. Various surgical treatment options have been reported. Laparoscopic resection of duodenal GIST is an advanced and challenging procedure requiring experience and good surgical technique. The laparoscopic limited resection of duodenal GIST is feasible and safe, reducing postoperative morbidity without compromising oncologic results. PMID:28281485

  17. The use of biomarkers in neuroendocrine tumours

    PubMed Central

    Khan, Mohid Shakil; Caplin, Martyn E

    2013-01-01

    The incidence and prevalence of neuroendocrine tumours (NETs) arising from the gastrointestinal tract are increasing. At the time of diagnosis, histological grade, based on Ki-67 proliferation index on a tumour biopsy or specimen, offers prognostication but with often lengthy survival, this may not reflect current tumour biology later in the disease course. Biomarkers, including plasma chromogranin A, urinary 5-hydroxyindole acetic acid and pancreatic specific hormones (insulin, gastrin, vasoactive intestinal peptide), have a role in diagnosis but despite being incorporated into routine clinical practice, there is a lack of robust prospectively collected data investigating their prognostic and predictive value. Given the increasing number of treatment options available for NETs and prolonged survival, there is no agreement on the order of treatment for individual NET patients but the emergence of novel biomarkers and validation of existing ones, in addition to better understanding of the molecular biology, may help solve this clinical problem. PMID:28839724

  18. [Pigmented ciliary body tumours: benign or malignant?].

    PubMed

    Vallejo-Vicente, E; Saornil-Álvarez, M A; López-Lara, F; García-Álvarez, C; de Frutos-Baraja, J M; Díez-Andino, P

    2013-12-01

    We report the cases of 2 women with a pigmented tumour in the ciliary body, one a melanocytoma and the other a melanoma, with different clinical manifestations. The first one presented with decreased visual acuity associated with recent growth of the tumour, as well as sectorial opacities of the lens and subluxation. The second one is asymptomatic and has been kept under observation for more than 30 years. Although the definitive diagnosis of a pigmented tumour of the ciliary body is only achieved by the histopathology study, the group of clinical features is a determining factor when a conservative treatment is indicated. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  19. Are natural antibodies involved in tumour defence?

    PubMed

    Bohn, J

    1999-09-01

    Natural antibodies (NAb) are found in the serum of healthy individuals. These antibodies are produced without any apparent specific antigenic stimulation. They are one part of the circulating immunoglobulins and are found in virtually all vertebrate species. NAb react to various self- and non-self antigens. A protective function in different infection models could be demonstrated. Several groups have reported the ability of NAb to bind to tumour cells. Their possible role in tumour defence is documented in mice. The present status of attempts to characterise the role of NAb in tumour defence is discussed, particularly as regards the human immune system. This paper focuses on antibody cell interactions and discusses the genetic background of the Nab-producing B-cells.

  20. Autoimmune pancreatitis mimicking Klatskin tumour on radiology.

    PubMed

    Hadi, Yousaf Bashir; Sohail, Abdul Malik Amir Humza; Haider, Zishan

    2015-04-09

    Autoimmune pancreatitis (AIP) is categorised into two distinct types, AIP type 1 and 2. Although there can be multisystem involvement, rarely, the cholangitis associated with AIP can present radiologically in a manner similar to that of Klatskin tumour. We present the case of a 65-year-old man who was almost misdiagnosed with a Klatskin tumour because of the similarity in radiological features of the two aforementioned clinical entities. The patient presented with a history of jaundice, pruritus and abdominal pain, and work up showed deranged liver function tests, elevated cancer antigen 19-9 levels and positive antinuclear antibodies. CT scan of the abdomen showed findings suggestive of Klatskin tumour but due to diffuse enlargement of the pancreas and surrounding low-attenuation halo found on a closer review, a diagnosis of AIP was performed. The patient was started on standard corticosteroid therapy and responded well, with complete resolution of the radiological findings.

  1. Tumours of the foot and ankle.

    PubMed

    Khan, Zeeshan; Hussain, Shakir; Carter, Simon R

    2015-09-01

    Sarcomas are rare tumours and particularly rarer in the foot and ankle region. The complex anatomy of the foot and ankle makes it unique and hence poses a challenge to the surgeon for limb salvage surgery. Other lesions found in the foot and ankle region are benign bone and soft tissue tumours, metastasis and infection. The purpose of this article is to discuss the relevance of the complex anatomy of the foot and ankle in relation to tumours, clinical features, their general management principles and further discussion about some of the more common bone and soft tissue lesions. Discussion of every single bone and soft tissue lesion in the foot and ankle region is beyond the scope of this article.

  2. Brain tumour-associated status epilepticus.

    PubMed

    Goonawardena, Janindu; Marshman, Laurence A G; Drummond, Katharine J

    2015-01-01

    We have reviewed the scant literature on status epilepticus in patients with brain tumours. Patients with brain tumour-associated epilepsy (TAE) appear less likely to develop status epilepticus (TASE) than patients with epilepsy in the general population (EGP) are to develop status epilepticus (SEGP). TASE is associated with lesions in similar locations as TAE; in particular, the frontal lobes. However, in contrast to TAE, where seizures commence early in the course of the disease or at presentation, TASE is more likely to occur later in the disease course and herald tumour progression. In marked contrast to TAE, where epilepsy risk is inversely proportional to Word Health Organization tumour grade, TASE risk appears to be directly proportional to tumour grade (high grade gliomas appear singularly predisposed). Whilst anti-epileptic drug (AED) resistance is more common in TAE than EGP (with resistance directly proportional to tumour grade and frontal location), TASE appears paradoxically more responsive to simple AED regimes than either TAE or SEGP. Although some results suggest that mortality may be higher with TASE than with SEGP, it is likely that (as with SEGP) the major determinant of mortality is the underlying disease process. Because all such data have been derived from retrospective studies, because TASE and SEGP are less common than TAE and EGP, and because TASE and SEGP classification has often been inconsistent, findings can only be considered preliminary: multi-centre, prospective studies are required. Whilst preliminary, our review suggests that TASE has a distinct clinical profile compared to TAE and SEGP. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Clinical application of tumour markers: a review.

    PubMed

    Amayo, A A; Kuria, J G

    2009-12-01

    Tumour markers have made a difference to oncology practice. They can be used in screening, diagnosis, prognostication and assessment of treatment efficacy. Reports on tumour marker usage suggest that many clinicians assume that a biomarker for a particular cancer can be effectively used for all these indications. This assumption is incorrect. Several guidelines have been published to inform clinicians on effective utilisation of these tests. To outline the recommended uses of the most commonly requested tumours markers in clinical practice. A hand search of literature on the recommended use of carcinoembryonic antigen (CEA), alphafetoprotein (AFP), prostate specific antigen (PSA), CA-125 and CA-19.9. Systematic reviews and prospective randomised clinical trials of tumour marker applications were also looked at. Five key journals and reference lists of relevant studies were considered. Two authors abstracted relevant data independently. Emphasis was given to guidelines from expert panels. The quality of the guidelines was assessed by availability of level of evidence supporting the recommendations. Several national and international expert groups have developed guidelines for use of markers for most cancers. CEA, AFP, PSA, CA-125 and CA-19.9 are validated for use in treatment monitoring of colorectal, hepatocellular, prostatic, ovarian and pancreatic carcinomas respectively. AFP and PSA are also useful for cancer screening in high risk groups. CA-125 has limited role in screening while CEA and CA 19.9 are not recommended for cancer screening. Not all currently available tumour markers can be used for screening and diagnosis of malignancies. Adherence to recommendations on tumour marker utilisation will improve the cost-effectiveness of these tests.

  4. Cytomorphology of neuroendocrine tumours of the gallbladder.

    PubMed

    Yadav, R; Jain, D; Mathur, S R; Iyer, V K

    2016-04-01

    Gallbladder neuroendocrine tumours (GB-NETs) are rare and account for 0.5% of all NETs. GB-NETs have an aggressive behaviour, which depends on the tumour grade. The cytomorphological spectrum of these tumours has never been described in detail. The present study evaluates the cytological features of GB-NETs and grades them according to the World Health Organization (WHO) classification. Furthermore, the expression of thyroid transcription factor-1 (TTF-1) has not been investigated previously in GB-NETs, although found in a subset of extrapulmonary NETs. Twenty cases of GB-NET among 875 gallbladder carcinomas diagnosed by ultrasound-guided fine needle aspiration cytology (FNAC) over a period of nearly 4 years were studied. The following parameters were evaluated: architectural pattern, nuclear chromatin, nucleoli, mitoses, necrosis, moulding, apoptosis and smudge cells. Cases were categorized into well-differentiated (grades 1 and 2), small cell carcinoma (SCC) (grade 3) and mixed adenoneuroendocrine carcinoma. Nuclear positivity for TTF-1 was considered as positive. Morphologically, tumour cells were mainly arranged in rosettes in the well-differentiated category; sudden anisonucleosis and rare nuclear moulding with or without mitotic figures were other features. Eleven cases of SCC showed prominent nuclear moulding with frequent smudge cells, mitoses, apoptosis and necrosis. Three mixed adenoneuroendocrine carcinomas showed papillary fragments and an acinar arrangement of tumour cells. Four of the nine SCCs in which TTF-1 was evaluated on de-stained smears showed nuclear positivity. Histopathology was available in two SCCs and showed morphology similar to FNAC. Cytology plays an important role in the diagnosis of GB-NETs for appropriate subtype characterization, which is necessary for the prognostication of these tumours. TTF-1 may not be used for the differentiation of gallbladder SCCs from pulmonary SCCs. © 2015 John Wiley & Sons Ltd.

  5. Investigating citrullinated proteins in tumour cell lines

    PubMed Central

    2013-01-01

    Background The conversion of arginine into citrulline, termed citrullination, has important consequences for the structure and function of proteins. Studies have found PADI4, an enzyme performing citrullination, to be highly expressed in a variety of malignant tumours and have shown that PADI4 participates in the process of tumorigenesis. However, as citrullinated proteins have not been systematically investigated in tumours, the present study aimed to identify novel citrullinated proteins in tumours by 2-D western blotting (2-D WB). Methods Two identical two-dimensional electrophoresis (2-DE) gels were prepared using extracts from ECA, H292, HeLa, HEPG2, Lovo, MCF-7, PANC-1, SGC, and SKOV3 tumour cell lines. The expression profiles on a 2-DE gel were trans-blotted to PVDF membranes, and the blots were then probed with an anti-citrulline antibody. By comparing the 2-DE profile with the parallel 2-D WB profile at a global level, protein spots with immuno-signals were collected from the second 2-DE gel and identified using mass spectrometry. Immunoprecipitation was used to verify the expression and citrullination of the targeted proteins in tumour cell lines. Results 2-D WB and mass spectrometry identified citrullinated α-enolase (ENO1), heat shock protein 60 (HSP60), keratin 8 (KRT8), tubulin beta (TUBB), T cell receptor chain and vimentin in these cell lines. Immunoprecipitation analyses verified the expression and citrullination of ENO1, HSP60, KRT8, and TUBB in the total protein lysates of the tumour cell lines. Conclusions The citrullination of these proteins suggests a new mechanism in the tumorigenic process. PMID:24099319

  6. Bone histomorphometric evaluation of a clinically fused titanium tumour cage in a child.

    PubMed

    van Dijk, M; Smit, Th H; Burger, E H; Wuisman, P I M J

    2002-10-01

    An intervertebral titanium tumour cage was implanted in a 2-year-old-girl after T11 spondylectomy due to Ewing sarcoma. After 2-years' follow-up without evidence of recurrence, the titanium cage was explanted to correct spinal deformity and to allow normal spinal growth development. Radiological follow-up and surgical exploration at the time of retrieval suggested fusion of the segment. Histologic evaluation, however, demonstrated ingrowth of trabecular bone, but without bridging trabecular bone. The distance between the opposing bone fronts measured 1.5 mm and the viable bone volume (BV/TV) within the cage was 36%. Histologic evaluation demonstrated that bone formation was still an ongoing process in the fusion zone 2 years after implantation.

  7. Is visual radiological evaluation of liver tumour burden in patients with neuroendocrine tumours reproducible?

    PubMed Central

    Hentic, Olivia; Vullierme, Marie-Pierre; Lagadec, Matthieu; Ronot, Maxime; Ruszniewski, Philippe; Vilgrain, Valérie

    2017-01-01

    Background Visual semi-quantitative assessment of liver tumour burden for neuroendocrine tumour liver metastases is often used in patient management and outcome. However, published data on the reproducibility of these evaluations are lacking. Objective The aim of this study was to evaluate the interobserver and intraobserver agreement of a visual semi-quantitative assessment of liver tumour burden using CT scan. Methods Fifty consecutive patients (24 men and 26 women, mean aged 54 years) were retrospectively reviewed by four readers (two senior radiologists, one junior radiologist and one gastroenterologist) who assessed the liver tumour burden based on a visual semi-quantitative method with four classes (0–10, 11–25, 26–50 and ≥50%). Interobserver and intraobserver agreement were assessed by weighted kappa coefficient and percentage of agreement. The intraclass correlation was calculated. Results Agreement among the four observers for the evaluation of liver tumour burden was substantial, ranging from 0.62 to 0.73 (P < 0.0001). The intraclass coefficient was 0.977 (P < 0.0001). Intraobserver agreement was 0.78 and ICC was 0.97. Conclusion Reproducibility of the visual semi-quantitative evaluation of liver tumour burden is good and is independent of the level of experience of the readers. We therefore suggest that clinical studies in patients with neuroendocrine liver metastases use this method to categorise liver tumour burden. PMID:28069898

  8. The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity

    PubMed Central

    Laoui, Damya; Keirsse, Jiri; Morias, Yannick; Van Overmeire, Eva; Geeraerts, Xenia; Elkrim, Yvon; Kiss, Mate; Bolli, Evangelia; Lahmar, Qods; Sichien, Dorine; Serneels, Jens; Scott, Charlotte L.; Boon, Louis; De Baetselier, Patrick; Mazzone, Massimiliano; Guilliams, Martin; Van Ginderachter, Jo A.

    2016-01-01

    Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets. Monocyte-derived TADCs are prominent in tumour antigen uptake, but lack strong T-cell stimulatory capacity due to NO-mediated immunosuppression. Pre-cDC-derived TADCs have lymph node migratory potential, whereby cDC1s efficiently activate CD8+ T cells and cDC2s induce Th17 cells. Mice vaccinated with cDC2s displayed a reduced tumour growth accompanied by a reprogramming of pro-tumoural TAMs and a reduction of MDSCs, while cDC1 vaccination strongly induces anti-tumour CTLs. Our data might prove important for therapeutic interventions targeted at specific TADC subsets or their precursors. PMID:28008905

  9. The tumour suppressor C/EBPδ inhibits FBXW7 expression and promotes mammary tumour metastasis

    PubMed Central

    Balamurugan, Kuppusamy; Wang, Ju-Ming; Tsai, Hsin-Hwa; Sharan, Shikha; Anver, Miriam; Leighty, Robert; Sterneck, Esta

    2010-01-01

    Inflammation and hypoxia are known to promote the metastatic progression of tumours. The CCAAT/enhancer-binding protein-δ (C/EBPδ, CEBPD) is an inflammatory response gene and candidate tumour suppressor, but its physiological role in tumourigenesis in vivo is unknown. Here, we demonstrate a tumour suppressor function of C/EBPδ using transgenic mice overexpressing the Neu/Her2/ERBB2 proto-oncogene in the mammary gland. Unexpectedly, this study also revealed that C/EBPδ is necessary for efficient tumour metastasis. We show that C/EBPδ is induced by hypoxia in tumours in vivo and in breast tumour cells in vitro, and that C/EBPδ-deficient cells exhibit reduced glycolytic metabolism and cell viability under hypoxia. C/EBPδ supports CXCR4 expression. On the other hand, C/EBPδ directly inhibits expression of the tumour suppressor F-box and WD repeat-domain containing 7 gene (FBXW7, FBW7, AGO, Cdc4), encoding an F-box protein that promotes degradation of the mammalian target of rapamycin (mTOR). Consequently, C/EBPδ enhances mTOR/AKT/S6K1 signalling and augments translation and activity of hypoxia-inducible factor-1α (HIF-1α), which is necessary for hypoxia adaptation. This work provides new insight into the mechanisms by which metastasis-promoting signals are induced specifically under hypoxia. PMID:21076392

  10. Human Papillomavirus-related tumours of the oropharynx display a lower tumour hypoxia signature.

    PubMed

    Hanns, Elodie; Job, Sylvie; Coliat, Pierre; Wasylyk, Christine; Ramolu, Ludivine; Pencreach, Erwan; Suarez-Carmona, Meggy; Herfs, Michael; Ledrappier, Sonia; Macabre, Christine; Abecassis, Joseph; Wasylyk, Bohdan; Jung, Alain C

    2015-09-01

    Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) patients have improved prognosis compared to other head and neck (HNSCC) cancers. Since poor prognosis is associated with tumour hypoxia, we studied whether the hypoxic response is different in HPV-related cells and tumours. HPV-positive and -negative cells were incubated in hypoxia and analyzed by qRTPCR, western blotting and cell proliferation assays. Tumours formed by xenografting these cells in nude mice were studied by IHC. HNSCC patient samples were analyzed by unsupervised clustering of hypoxia-related gene expression, quantitative real-time PCR (qRTPCR) and immunohistochemical (IHC) detection of neo-blood vessels. HPV-positive and -negative cells responded differently to hypoxia, in terms of gene expression (HIF-1α, PHD-3, GLUT-1 and VEGF-A) and cell survival. Tumour xenografts formed by HPV-positive cells had fewer hypoxic areas than those formed by HPV-negative cells. HPV related tumours were less hypoxic, expressed lower levels of hypoxia-responsive genes, and had a higher density of neo-blood vessels. HPV-related OSCC display lower tumour hypoxia, which could be linked to the distinct intrinsic abilities of HPV-positive tumour cells to adapt to hypoxia and to their better prognosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

    PubMed Central

    Trubelja, Alen

    2017-01-01

    Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening. In particular, tumour-on-a-chip microdevices allow well-controlled microscopic studies of the interaction among tumour cells, immune cells and cells in the TME, of which simple tissue cultures and animal models are not amenable to do. The challenges in developing the next-generation tumour-on-a-chip technology are also discussed. PMID:28637915

  12. Anti-tumour strategies aiming to target tumour-associated macrophages

    PubMed Central

    Tang, Xiaoqiang; Mo, Chunfen; Wang, Yongsheng; Wei, Dandan; Xiao, Hengyi

    2013-01-01

    Tumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy. PMID:23113570

  13. Optimization of tumour control probability for heterogeneous tumours in fractionated radiotherapy treatment protocols.

    PubMed

    Levin-Plotnik, D; Hamilton, R J

    2004-02-07

    We find the dose distribution that maximizes the tumour control probability (TCP) for a fixed mean tumour dose per fraction. We consider a heterogeneous tumour volume having a radiation response characterized by the linear quadratic model with heterogeneous radiosensitivity and repopulation rate that may vary in time. Using variational calculus methods a general solution is obtained. We demonstrate the spatial dependence of the optimal dose distribution by explicitly evaluating the solution for different functional forms of the tumour properties. For homogeneous radiosensitivity and growth rate, we find that the dose distribution that maximizes TCP is homogeneous when the clonogen cell density is homogeneous, while for a heterogeneous initial tumour density we find that the first dose fraction is inhomogeneous, which homogenizes the clonogen cell density, and subsequent dose fractions are homogeneous. When the tumour properties have explicit spatial dependence, we show that the spatial variation of the optimized dose distribution is insensitive to the functional form. However, the dose distribution and tumour clonogen density are sensitive to the value of the repopulation rate. The optimized dose distribution yields a higher TCP than a typical clinical dose distribution or a homogeneous dose distribution.

  14. Plate fixation of prostheses after segmental resection for bone tumours.

    PubMed

    Coathup, M J; Cobb, J P; Walker, P S; Blunn, G W

    2000-11-01

    This study investigated the concept of using plates to attach endoprostheses to bone after segmental resection for bone tumours in an animal model. Titanium alloy plates integrated with the prosthesis and coated with hydroxyapatite were attached to bone by screws. This type of uncemented fixation relied on the induction of periosteal bone formation into and around the plates to secure the implant to bone. Two, three, and six-slotted plate designs were investigated. On retrieval, each plate was securely fixed by new bone. Bone apposition on the external surface of the plates occurred through a combination of periosteal bone production, invasion of bone through slots in the plate, and bone growth over the ends of the plates. Most plates became incorporated into a remodelled cortex. Higher bone turnover rates (microm day(-1)) were seen in bone in the slots of the plate compared with normal cortical bone turnover (p < 0.05). Significantly higher rates of turnover were measured beneath slotted parts of the plates compared with regions below the unslotted parts (p < 0.05). The cross-sectional area of bone surrounding the six-plate implant design was significantly higher than that of the three-plate (p < 0.05) and two-plate (p < 0.05) designs. In addition, significantly more bone formed adjacent to the six-plated implant design compared with that in the contralateral limb (p = 0.002). However, no significant difference was found when the total cortical area around the three-plated design was compared with that of the contralateral limb (p = 0.63). In contrast, significantly less bone was measured adjacent to the two-plate design than in the untreated limb (p = 0.001). Image analysis also demonstrated increased cortical porosity adjacent to the six-plate design compared with the three-plate (p = 0.004) and two-plate (p < 0.05) designs. Finite element analysis demonstrated that the six and three-plate designs increased the second moment of area compared with that in the

  15. Coordinated regulation of myeloid cells by tumours.

    PubMed

    Gabrilovich, Dmitry I; Ostrand-Rosenberg, Suzanne; Bronte, Vincenzo

    2012-03-22

    Myeloid cells are the most abundant nucleated haematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The three groups of terminally differentiated myeloid cells - macrophages, dendritic cells and granulocytes - are essential for the normal function of both the innate and adaptive immune systems. Mounting evidence indicates that the tumour microenvironment alters myeloid cells and can convert them into potent immunosuppressive cells. Here, we consider myeloid cells as an intricately connected, complex, single system and we focus on how tumours manipulate the myeloid system to evade the host immune response.

  16. Malignant tumours in patients with HIV infection.

    PubMed Central

    Tirelli, U.; Franceschi, S.; Carbone, A.

    1994-01-01

    One of the most important though somewhat neglected aspects of research in HIV infection concerns the development, clinicopathological characteristics, and treatment of malignant tumours in infected patients. With the improved survival of patients with AIDS owing to the better prevention and treatment of infectious complications there may well be an increase in AIDS related malignancies. This paper reviews the epidemiology, pathology, and treatment of malignant tumours in patients with HIV. Images p1149-a p1149-b p1149-c FIG 1 FIG 2 FIG 3 p1151-a p1151-b p1151-c PMID:8173459

  17. Stochastic Gompertz model of tumour cell growth.

    PubMed

    Lo, C F

    2007-09-21

    In this communication, based upon the deterministic Gompertz law of cell growth, a stochastic model in tumour growth is proposed. This model takes account of both cell fission and mortality too. The corresponding density function of the size of the tumour cells obeys a functional Fokker--Planck equation which can be solved analytically. It is found that the density function exhibits an interesting "multi-peak" structure generated by cell fission as time evolves. Within this framework the action of therapy is also examined by simply incorporating a therapy term into the deterministic cell growth term.

  18. Coordinated regulation of myeloid cells by tumours

    PubMed Central

    Gabrilovich, Dmitry I.; Ostrand-Rosenberg, Suzanne; Bronte, Vincenzo

    2013-01-01

    Myeloid cells are the most abundant nucleated hematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The three groups of terminally differentiated myeloid cells — macrophages, dendritic cells and granulocytes — are essential for the normal function of both the innate and adaptive immune systems. Mounting evidence indicates that the tumour microenvironment alters myeloid cells and can convert them into potent immune suppressive cells. Here, we consider myeloid cells as an intricately connected, complex, single system and we focus on how tumours manipulate the myeloid system to evade the host immune response. PMID:22437938

  19. Nine cases of Merkel cell tumour.

    PubMed Central

    Bose, A

    1997-01-01

    Merkel cell tumour is an aggressive neuroendocrine neoplasm arising in the dermis. Although only a few hundred cases have been reported worldwide, nine were seen in Nottingham between 1985 and early 1994. The patients were five women and four men age 63-88. One was the first Afro-Caribbean reported to have such a tumour. In no case was the diagnosis made clinically; histological and histochemical examination was necessary. Three of the patients died quickly with metastatic disease. The primary treatment is surgical excision. For advanced disease, radiotherapy is commonly beneficial. Images Figure 1 Figure 2 Figure 3 PMID:9306997

  20. A Large Extragnathic Keratocystic Odontogenic Tumour

    PubMed Central

    Bavle, Radhika M.; Muniswamappa, Sudhakara; Narasimhamurthy, Srinath

    2015-01-01

    Odontogenic keratocysts (OKCs) are developmental cysts which occur typically in the jawbones. They present more commonly in the posterior mandible of young adults than the maxilla. OKCs have been reclassified under odontogenic tumours in 2005 by the WHO and have since been termed as keratocystic odontogenic tumours (KCOTs). Here we report a case of a recurrent buccal lesion in a 62-year-old man which was provisionally diagnosed as a space infection (buccal abscess) but surprisingly turned out to be a soft tissue KCOT in an unusual location on histopathologic examination. PMID:26770859

  1. Peri-Implant Diseases

    MedlinePlus

    ... Alcohol Consumption and Gum Health Workshop on Regeneration Periodontal Disease More Prevalent among Ethnic Minorities Dental Implants Periodontal ... factors for developing peri-implant disease include previous periodontal disease diagnosis, poor plaque control, smoking , and diabetes . It ...

  2. Implants for lucky few

    NASA Astrophysics Data System (ADS)

    Brandon, David

    2011-08-01

    In his article "Vision of beauty" (May pp22-27), Richard Taylor points the way to fractal design for retinal implants and makes an enthusiastic case for incorporating such features into the next generation of such implants.

  3. Parotid gland metastases of distant primary tumours: A diagnostic challenge.

    PubMed

    Franzen, Achim M; Günzel, Thomas; Lieder, Anja

    2016-04-01

    Metastatic disease is common among parotid malignancies. The majority of primary tumours are located in the head and neck, but primary tumours below the clavicle must also be considered, especially in histological types not usually found in primary parotid or skin tumours. We performed 644 consecutive parotidectomies between 1980 and 2012. Benign tumours were found in 555 patients (86%) and malignant tumours in 89 patients (14%). Of 89 malignant tumours, 39 were metastases (44%). In 5 cases, the primary tumour was located below the clavicle (6% of malignant tumours). A carcinoma of the bronchus was subsequently diagnosed in three patients: one patient had breast carcinoma and one renal cell carcinoma. The majority of metastases in the parotid gland arise from primary tumours of the head and neck. In 10-20% of metastases, the primary tumour arises below the clavicle. Parotid metastases can be the first clinical manifestation of a malignant tumour, and can also occur years after curative intent treatment. Histopathology and immunohistochemistry will offer clues to a possible metastatic process and to primary tumour location. Parotidectomy with complete excision of the tumour can be a curative measure or form an essential part of symptom control and should be considered in all but the most moribund patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. The management of soft tissue tumours of the abdominal wall.

    PubMed

    Smith, H G; Tzanis, D; Messiou, C; Benson, C; van der Hage, J A; Fiore, M; Bonvalot, S; Hayes, A J

    2017-09-01

    Soft tissue tumours of the abdominal wall account for approximately 10% of all soft tissue tumours. Tumours at this site comprise a heterogeneous group of pathologies with distinct clinical behaviours and responses to treatment. The management of these tumours has largely been extrapolated from studies of soft tissue tumours at other sites. This review aims to summarise the existing data relating to abdominal wall tumours and suggest principles for managing soft tissue tumours at this site. Relevant articles were retrieved from a comprehensive literature search using the PubMed database. Key words included abdominal wall, soft tissue tumours, surgery, radiotherapy and chemotherapy. No restrictions on publication date were used. The most common pathologies presenting in the abdominal wall are desmoid tumours, soft-tissue sarcoma and dermatofibrosarcoma protuberans (DFSP). Desmoid tumours should be managed with an initial period of observation, with surgery reserved for progressive lesions. Surgery should be the primary treatment for soft-tissue sarcomas and DFSP, with radiotherapy reserved for large-high grade tumours and preferentially given pre-operatively. Abdominal wall tumours are rare and should be managed in centres with experience in the management of soft tissue tumours. Management should be tailored to the biological behaviour of specific pathologies. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  5. Cochlear Implants for Children.

    ERIC Educational Resources Information Center

    Hasenstab, M. Suzanne; Laughton, Joan

    1991-01-01

    The use of cochlear implants in children with profound bilateral hearing loss is discussed, focusing on how a cochlear implant works; steps in a cochlear implant program (evaluation, surgery, programing, and training); and rehabilitation procedures involved in auditory development and speech development. (JDD)

  6. 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.

  7. Adult Wilms’ Tumour: Case Report and Review of Literature

    PubMed Central

    Tiang, Kor Woi; Inglis, Po; Collins, Stuart

    2016-01-01

    Wilms’ tumour (nephroblastoma) is the most common renal tumour in children. Wilms’ tumour in adults is extremely rare and has a poorer prognosis than paediatric Wilms’ tumour. It is difficult to differentiate adult Wilms’ tumour from renal cell carcinoma based on radiological findings alone. The diagnosis in adults is often serendipitous following nephrectomy for presumed renal cell carcinoma. Because of the paucity of literature, there are no standard protocols for the management of adult Wilms’ tumour, and therefore, it is managed as per paediatric Wilms’ tumour. Herein, we report the case of adult Wilms’ tumour in a 43-year-old man, which was diagnosed unexpectedly following nephrectomy for presumed renal cell carcinoma. PMID:28326278

  8. Systematic pan-cancer analysis of tumour purity.

    PubMed

    Aran, Dvir; Sirota, Marina; Butte, Atul J

    2015-12-04

    The tumour microenvironment is the non-cancerous cells present in and around a tumour, including mainly immune cells, but also fibroblasts and cells that comprise supporting blood vessels. These non-cancerous components of the tumour may play an important role in cancer biology. They also have a strong influence on the genomic analysis of tumour samples, and may alter the biological interpretation of results. Here we present a systematic analysis using different measurement modalities of tumour purity in >10,000 samples across 21 cancer types from the Cancer Genome Atlas. Patients are stratified according to clinical features in an attempt to detect clinical differences driven by purity levels. We demonstrate the confounding effect of tumour purity on correlating and clustering tumours with transcriptomics data. Finally, using a differential expression method that accounts for tumour purity, we find an immunotherapy gene signature in several cancer types that is not detected by traditional differential expression analyses.

  9. Cutaneous location of atypical teratoid/rhabdoid tumour.

    PubMed

    Bellon, Nathalia; Fraitag, Sylvie; Miquel, Catherine; Salomon, Laurent J; Bourdeaut, Franck; Bodemer, Christine; Roujeau, Thomas; Zerah, Michel; Hadj-Rabia, Smail

    2014-07-01

    Atypical teratoid/rhabdoid tumour is a rare and highly malignant tumour of the posterior fossae nervous system that occurs in children especially in the first few years of life. Cutaneous location is not previously reported. A newborn boy was referred for both aqueductal stenosis detected antenatally and skin tags mimicking hamartoma. The cerebral tumour increased in size during a few months leading to both skin and cerebral biopsies. Integrase Interactor-1 (INI-1) immunostaining and tumoural and leukocytes INI-1 gene sequencing confirmed the atypical teratoid/rhabdoid tumour nature of the cerebral tumour. INI-1 immunostaining in skin biopsy confirmed the dermal location of rhabdoid tumour. Thus, unusual cutaneous lesions may be part of atypical teratoid/rhabdoid tumour. The loss of Integrase INI-1 on immunohistochemical staining is characteristic.

  10. Ileocaecal intussusception secondary to metastatic phyllodes tumour of the breast.

    PubMed

    Morcos, Basem B; Baker, Bilal; Hashem, Sameh A

    2010-09-01

    A patient with phyllodes tumour of the breast is discussed. During follow-up, she presented with intestinal obstruction caused by ileocaecal intussusception. The cause of the intussusception was metastatic phyllodes tumour, which is a unique presentation.

  11. Towards the Design of a Patient-Specific Virtual Tumour

    PubMed Central

    Caraguel, Flavien; Lesart, Anne-Cécile; Estève, François; van der Sanden, Boudewijn

    2016-01-01

    The design of a patient-specific virtual tumour is an important step towards Personalized Medicine. However this requires to capture the description of many key events of tumour development, including angiogenesis, matrix remodelling, hypoxia, and cell state heterogeneity that will all influence the tumour growth kinetics and degree of tumour invasiveness. To that end, an integrated hybrid and multiscale approach has been developed based on data acquired on a preclinical mouse model as a proof of concept. Fluorescence imaging is exploited to build case-specific virtual tumours. Numerical simulations show that the virtual tumour matches the characteristics and spatiotemporal evolution of its real counterpart. We achieved this by combining image analysis and physiological modelling to accurately described the evolution of different tumour cases over a month. The development of such models is essential since a dedicated virtual tumour would be the perfect tool to identify the optimum therapeutic strategies that would make Personalized Medicine truly reachable and achievable. PMID:28096895

  12. Intraoperative intravital microscopy permits the study of human tumour vessels

    PubMed Central

    Fisher, Daniel T.; Muhitch, Jason B.; Kim, Minhyung; Doyen, Kurt C.; Bogner, Paul N.; Evans, Sharon S.; Skitzki, Joseph J.

    2016-01-01

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID:26883450

  13. pH distributions in spontaneous and isotransplanted rat tumours.

    PubMed Central

    Kallinowski, F.; Vaupel, P.

    1988-01-01

    Spontaneous mammary tumours of the rat with various degrees of malignancy exhibit similar tissue pH distributions. The mean pH (+/- s.d.) of dysplasia is 7.05 +/- 0.20. In benign tumours the mean pH is 6.95 +/- 0.19 and in malignant tumours it is 6.94 +/- 0.19. In contrast, tumours with the same degree of malignancy but different histologies show different pH distributions. Benign tumours with a higher percentage of fibrous tissue exhibit less acidic pH values than those with larger portions of epithelial cells (delta pH = 0.38 pH units). The pH distribution in the benign tumours is independent of the tumour wet weight up to stages of very advanced growth. In the malignant tumours, a trend towards more acidic pH values is observed as the tumour mass enlarges. However, in tissue areas within a malignant tumour with gross, long-established necrosis the pH distribution is shifted towards more alkaline pH values. The pH distributions in spontaneous rat tumours are not significantly different from those obtained in isotransplanted Yoshida sarcomas (6.87 +/- 0.21). In the Yoshida sarcomas, mean pH values do not correlate with tumour size. However, a pH gradient from the rim to the centre of the tumours is found which coincides with the development of small, disseminated necroses in the tumour centre. It is concluded that pathology-related variations of tumour pH may be more important than the mode of tumour origin or the degree of malignancy. PMID:3179183

  14. Melanotic neuroectodermal tumour of infancy: a case report.

    PubMed

    Tam, Jessica; Cheung, Wa Sham; Senger, Christof; Reichman, Mark; Campbell, Karen M

    2015-01-01

    Melanotic neuroectodermal tumour of infancy is a rare benign pigmented tumour that typically appears in the first year of life. We report an atypical presentation of this tumour, associated with an erupted primary tooth in a 7-month-old boy. We discuss the clinical, radiographic and histologic features of this rare tumour, as well as its surgical management and the follow-up treatment plan.

  15. Malignant gonadal tumour formation in intersexual states

    PubMed Central

    Pigott, H. W. S.

    1975-01-01

    Two cases of malignant tumour are reported in phenotypically male hermaphrodites. The importance of establishing the presence of persistent Müllerian duct structures in pseudo-hermaphrodites is discussed in relation to prophylactic castration in anticipation of malignant change. ImagesFig. 1Fig. 2 PMID:1197157

  16. Analysis of nanoparticle delivery to tumours

    NASA Astrophysics Data System (ADS)

    Wilhelm, Stefan; Tavares, Anthony J.; Dai, Qin; Ohta, Seiichi; Audet, Julie; Dvorak, Harold F.; Chan, Warren C. W.

    2016-05-01

    Targeting nanoparticles to malignant tissues for improved diagnosis and therapy is a popular concept. However, after surveying the literature from the past 10 years, only 0.7% (median) of the administered nanoparticle dose is found to be delivered to a solid tumour. This has negative consequences on the translation of nanotechnology for human use with respect to manufacturing, cost, toxicity, and imaging and therapeutic efficacy. In this article, we conduct a multivariate analysis on the compiled data to reveal the contributions of nanoparticle physicochemical parameters, tumour models and cancer types on the low delivery efficiency. We explore the potential causes of the poor delivery efficiency from the perspectives of tumour biology (intercellular versus transcellular transport, enhanced permeability and retention effect, and physicochemical-dependent nanoparticle transport through the tumour stroma) as well as competing organs (mononuclear phagocytic and renal systems) and present a 30-year research strategy to overcome this fundamental limitation. Solving the nanoparticle delivery problem will accelerate the clinical translation of nanomedicine.

  17. Solitary fibrous tumour of the vagus nerve.

    PubMed

    Scholsem, Martin; Scholtes, Felix

    2012-04-01

    We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve root. This ninth case of immunohistologically confirmed cranial or spinal nerve SFT is the first of the vagus nerve.

  18. Vagal Schwannoma: A Rare Parapharyngeal Tumour

    PubMed Central

    Kamath, Panduranga M; Sreedharan, Suja S; Majeed, Nazeem A; Shenoy, Vijendra S

    2016-01-01

    Among the parapharyngeal tumours, salivary gland tumours are the commonest, followed by schwannomas, which are slow growing benign tumours. Half of the parapharyngeal schwannomas originate from the vagus. Complete surgical excision is the treatment of choice. We hereby present two cases of parapharyngeal schwannomas, one which had presented as an intraoral mass and the other as a swelling in the neck. The first case, a 57-year-old female patient complained of a slowly increasing swelling in the left side of the throat since 3 months, associated with pain and dysphagia. In the Contrast Enhanced CT scan of the neck, a well-defined cystic lesion with central enhancing solid components (4cm X 4.5cm X 3cm) was seen in the left parapharyngeal region. The second case, a 39-year-old male patient complained of a painless, gradually increasing swelling below the lobule of the right ear since one month. Examination revealed a solitary, nontender, firm and mobile swelling of 2cm X 2cm below the lobule of the right ear. In Contrast Enhanced CT scan of the neck, an enhancing lesion was seen involving the right parapharyngeal space, post-styloid compartment. Both the patients underwent trans-cervical surgical excision. Vagal nerve schwannoma is rare. The majority of the cases present with a slow growing neck swelling without neurological deficit. Complete surgical excision of the tumour is important to prevent recurrence. PMID:27190844

  19. Pineal parenchymal tumours and pineal cysts.

    PubMed

    Jouvet, A; Vasiljevic, A; Champier, J; Fèvre Montange, M

    2015-01-01

    Pineal parenchymal tumours (PPTs) and pineal cysts represent one third of the pineal region lesions. PPTs are subdivided into pineocytoma (PC), pineoblastoma (PB) and PPT with intermediate differentiation (PPTID). We report morphological and immunochemical features which permit to grade these tumours. The description of histopathological features and grading is based on a large cooperative series and on the WHO 2007 classification. PCs occur in adults between the third and the sixth decade of life. PBs typically occur in children. PPTIDs have a peak incidence in young adults between 20 and 40 years of age. There is no sex preference. PC is characterized by a uniform cell proliferation with large fibrillary pineocytomatous rosettes. PB is a high-density tumour composed of small blue cells with hyper-chromatic, round or carrot shaped nuclei. PPTIDs have lobulated or diffuse patterns. Grading is based on morphological features, count of mitoses and neurofilament protein (NFP) expression. PCs (grade I) have no mitosis and NFP is highly expressed in pineocytomatous rosettes. PBs (grade IV) are high mitotic tumours and present low or no expression of NFPs. PPTIDs are grade II when mitoses are fewer than 6 for 10 high-power fields and NFPs are expressed, and are grade III when mitoses are greater or equal to 6 or are fewer than 6 with NFPs lowly expressed. Pineal cysts may be differentiated from PPTs by the high expression of NFPs and no expression of Ki-67. Copyright © 2014. Published by Elsevier Masson SAS.

  20. Tetraploidy in BRCA2 breast tumours.

    PubMed

    Jonsdottir, Asta Bjork; Stefansson, Olafur Andri; Bjornsson, Johannes; Jonasson, Jon G; Ogmundsdottir, Helga M; Eyfjord, Jorunn E

    2012-02-01

    Tetraploidy and aneuploidy can be caused by cell division errors and are frequently observed in many human carcinomas. We have recently reported delayed cytokinesis in primary human fibroblasts from BRCA2 mutation carriers, implying a function for the BRCA2 tumour suppressor in completion of cell division. Here, we address ploidy aberrations in breast tumours derived from BRCA2 germline mutation carriers. Ploidy aberrations were evaluated from flow cytometry histograms on selected breast tumour samples (n=236), previously screened for local BRCA mutations. The ploidy between BRCA2-mutated (n=71) and matched sporadic (n=165) cancers was compared. Differences in ploidy distribution were examined with respect to molecular tumour subtypes, previously defined by immunohistochemistry on tissue microarray sections. Tetraploidy was significantly 3 times more common in BRCA2 breast cancers than sporadic. However, no differences were found in the overall ploidy distribution between BRCA2-mutation carriers and non-carriers. In BRCA2 cancers, tetraploidy was associated with luminal characteristics. The increased frequency of tetraploidy in BRCA2 associated cancers may be linked to cell division errors, particularly cytokinesis. Additionally, tetraploidy emerges predominantly in BRCA2 breast cancers displaying luminal rather than triple-negative phenotypes.

  1. Congenital epulis: A rare benign tumour.

    PubMed

    Wong, D K C; Ramli, R; Muhaizan, W M; Primuharsa Putra, S H A

    2016-10-01

    Congenital epulis is a rare benign pedunculated tumour of the oral cavity arising from the alveolar ridges. It is usually detected in newborns and can be successfully resected surgically. We report a case of a newborn baby who had a 5x3x3cm pedunculated lobar mass arising from the upper alveolar ridge.

  2. Circulating tumour markers in breast cancer.

    PubMed

    Seregni, Ettore; Coli, Antonio; Mazzucca, Nicola

    2004-06-01

    A large number of markers have been proposed for breast cancer, but among them only CA 15.3, CEA and cytokeratins (i.e. TPA, TPS and Cyfra 21.1) are currently used in clinical practice. Serum marker levels reflect tumour burden and for this reason they are not sensitive enough to be used for screening and early diagnosis of primary breast cancer. By contrast, the role of tumour markers is established in the diagnosis of recurrent disease and in the evaluation of response to treatment. In the former case, however, prospective randomised studies are required to demonstrate any survival benefit when earlier therapeutic interventions are instituted upon elevation of serum markers. In the second case, tumour marker evaluation represents a simple, objective method for monitoring of therapeutic response that seems to offer significant advantages over conventional imaging methods (e.g. objectivity, modifications in tumour biology). Furthermore, research studies are ongoing to identify and validate new biochemical parameters which can be of use not only in advanced disease but also in other stages of the diagnostic work-up of breast cancer.

  3. Peripheral primitive neuroectodermal tumour of the orbit.

    PubMed

    Romero, Ricardo; Castano, Ananda; Abelairas, Jose; Peralta, Jesus; Garcia-Cabezas, Miguel A; Sanchez-Orgaz, Margarita; Arbizu, Alvaro; Vallejo-Garcia, Jose

    2011-07-01

    Peripheral primitive neuroectodermal tumours (pPNETs) are a group of soft-tissue tumours of neuroepithelial origin that arise outside the central and sympathetic nervous system. Orbital location is infrequent, and to the best of the authors' knowledge only 16 cases have been reported in the literature. With this article, the authors report the demographics and clinical characteristics, diagnostic features, differential diagnosis, prognosis and therapeutic options of primary orbital peripheral primitive neuroectodermal tumour, based on their patients and on the cases reported in the literature to date. A differential diagnosis should be made with other small round cell tumours; immunohistochemical and ultrastructural techniques are essential for this purpose. Although bone invasion and extraorbital extension are possible, systemic metastases are uncommon in the cases of orbital pPNETs. Surgery has been the initial treatment in most cases; chemotherapy with or without radiotherapy is considered the best additional treatment. The orbital pPNET could be less aggressive than other forms of pPNETs, since most of the patients reported were alive after the follow-up period (at least 6 months).

  4. Tumour immunomodulation: mucins in resistance to initiation and maturation of immune response against tumours.

    PubMed

    Anandkumar, A; Devaraj, H

    2013-07-01

    Mucins are high molecular weight glycoproteins designed for cellular protection and sensing the external environment. Aberrant glycosylation and altered mucin expression seen in cancers are implicated in mucin-dependent refraction to immunosurveilance and immunosuppressive induction around the tumour. Although mucins provide molecular targets for immune system's tumour recognition, their characteristics dictate that the nature of immune response required for recognition and lyses of mucin-expressing tumours needs to follow predominantly a MHC-unrestricted αβ TCR-mediated effector cell response. Frequent loss of dendritic cells maturation and elimination of reactive lymphocytes altered adhesive and anti-adhesive properties of the mucins, promote tumour survival and escape from the immune response. © 2013 John Wiley & Sons Ltd.

  5. Neuropsychological Differences between Survivors of Supratentorial and Infratentorial Brain Tumours

    ERIC Educational Resources Information Center

    Patel, S. K.; Mullins, W. A.; O'Neil, S. H.; Wilson, K.

    2011-01-01

    Background: The purpose of this study is to evaluate the relationship between brain tumour location and core areas of cognitive and behavioural functioning for paediatric brain tumour survivors. The extant literature both supports and refutes an association between paediatric brain tumour location and neurocognitive outcomes. We examined…

  6. Neuropsychological Differences between Survivors of Supratentorial and Infratentorial Brain Tumours

    ERIC Educational Resources Information Center

    Patel, S. K.; Mullins, W. A.; O'Neil, S. H.; Wilson, K.

    2011-01-01

    Background: The purpose of this study is to evaluate the relationship between brain tumour location and core areas of cognitive and behavioural functioning for paediatric brain tumour survivors. The extant literature both supports and refutes an association between paediatric brain tumour location and neurocognitive outcomes. We examined…

  7. Frequent MED12 mutations in phyllodes tumours of the breast

    PubMed Central

    Yoshida, M; Sekine, S; Ogawa, R; Yoshida, H; Maeshima, A; Kanai, Y; Kinoshita, T; Ochiai, A

    2015-01-01

    Background: Phyllodes tumours are rare fibroepithelial tumours of the breast, that include benign, borderline, and malignant lesions. Although the molecular basis of phyllodes tumours largely remains unknown, a recent exome study identified MED12 mutations as a sole recurrent genetic alteration in fibroadenoma, a common benign fibroepithelial tumour that shares some histological features with the phyllodes tumour. Methods: Forty-six phyllodes tumours and 58 fibroadenomas of the breast were analysed for MED12 mutations by using Sanger sequencing. Results: MED12 mutations were identified in 37 out of the 46 phyllodes tumours (80%). The prevalence of MED12 mutations was similar among benign (15/18, 83%), borderline (12/15, 80%), and malignant tumours (10/13, 77%). MED12 mutations were also identified in 36 of the 58 fibroadenomas (62%). The mutations were frequent among intracanalicular-type (24/32, 75%) and complex-type lesions (4/6, 67%), but were significantly less common among the pericanalicular-type lesions (8/20, 40%). A microdissection-based analysis showed that MED12 mutations were confined to the stromal components in both phyllodes tumours and fibroadenomas. Conclusions: MED12 mutations were frequent among the phyllodes tumours of the breast, regardless of the tumour grade. Phyllodes tumours and fibroadenomas share, at least in part, a common genetic background. PMID:25839987

  8. Frequent MED12 mutations in phyllodes tumours of the breast.

    PubMed

    Yoshida, M; Sekine, S; Ogawa, R; Yoshida, H; Maeshima, A; Kanai, Y; Kinoshita, T; Ochiai, A

    2015-05-12

    Phyllodes tumours are rare fibroepithelial tumours of the breast, that include benign, borderline, and malignant lesions. Although the molecular basis of phyllodes tumours largely remains unknown, a recent exome study identified MED12 mutations as a sole recurrent genetic alteration in fibroadenoma, a common benign fibroepithelial tumour that shares some histological features with the phyllodes tumour. Forty-six phyllodes tumours and 58 fibroadenomas of the breast were analysed for MED12 mutations by using Sanger sequencing. MED12 mutations were identified in 37 out of the 46 phyllodes tumours (80%). The prevalence of MED12 mutations was similar among benign (15/18, 83%), borderline (12/15, 80%), and malignant tumours (10/13, 77%). MED12 mutations were also identified in 36 of the 58 fibroadenomas (62%). The mutations were frequent among intracanalicular-type (24/32, 75%) and complex-type lesions (4/6, 67%), but were significantly less common among the pericanalicular-type lesions (8/20, 40%). A microdissection-based analysis showed that MED12 mutations were confined to the stromal components in both phyllodes tumours and fibroadenomas. MED12 mutations were frequent among the phyllodes tumours of the breast, regardless of the tumour grade. Phyllodes tumours and fibroadenomas share, at least in part, a common genetic background.

  9. [Malignant germinal tumours of the mediastinum: diagnosis and treatment].

    PubMed

    Lemarié, E

    2004-11-01

    Mediastinal germinal tumours are composed of tissues resembling those that follow one another during embryo development, by differentiation of the primordial and extraembryonic layers. Such practice separates the mature teratomas (benign), seminomas and non-seminomatous germinal tumours (NSGT). Platin-based chemotherapy has shattered the prognosis of such tumours.

  10. Probing Tumour Proteostasis and the UPR with Serum Markers.

    PubMed

    Galmiche, Antoine; Sauzay, Chloé; Houessinon, Aline; Chauffert, Bruno; Pluquet, Olivier

    2016-05-01

    Tumour proteostasis and the unfolded protein response (UPR) are emerging drivers of tumour progression and important determinants of clinical efficacy of cancer therapy. Recent findings indicate that they also regulate the production of protein tumour markers. Here, we discuss how this new knowledge opens up new perspectives for cancer therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Slow growth of an untreated Wilms's tumour in the adolescent.

    PubMed Central

    Rogers, P C; Wood, B J; Smith, D F; Teasdale, J M

    1978-01-01

    Retrospective radiological documentation of a growing Wilms's tumour in rare. Considered to be a relatively rapidly growing tumour, we present a case where there was adequate radiological evidence of a Wilms's tumour 4 years before the clinical metastatic presentation. Images Fig. 1 Fig. 2 Fig. 3 PMID:215089

  12. The mechanical microenvironment in cancer: How physics affects tumours.

    PubMed

    Nagelkerke, Anika; Bussink, Johan; Rowan, Alan E; Span, Paul N

    2015-12-01

    The tumour microenvironment contributes greatly to the response of tumour cells. It consists of chemical gradients, for example of oxygen and nutrients. However, a physical environment is also present. Apart from chemical input, cells also receive physical signals. Tumours display unique mechanical properties: they are a lot stiffer than normal tissue. This may be either a cause or a consequence of cancer, but literature suggests it has a major impact on tumour cells as will be described in this review. The mechanical microenvironment may cause malignant transformation, possibly through activation of oncogenic pathways and inhibition of tumour suppressor genes. In addition, the mechanical microenvironment may promote tumour progression by influencing processes such as epithelial-to-mesenchymal transition, enhancing cell survival through autophagy, but also affects sensitivity of tumour cells to therapeutics. Furthermore, multiple intracellular signalling pathways prove sensitive to the mechanical properties of the microenvironment. It appears the increased stiffness is unlikely to be caused by increased stiffness of the tumour cells themselves. However, there are indications that tumours display a higher cell density, making them more rigid. In addition, increased matrix deposition in the tumour, as well as increased interstitial fluid pressure may account for the increased stiffness of tumours. Overall, tumour mechanics are significantly different from normal tissue. Therefore, this feature should be further explored for use in cancer prevention, detection and treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma.

    PubMed

    De Mattos-Arruda, Leticia; Mayor, Regina; Ng, Charlotte K Y; Weigelt, Britta; Martínez-Ricarte, Francisco; Torrejon, Davis; Oliveira, Mafalda; Arias, Alexandra; Raventos, Carolina; Tang, Jiabin; Guerini-Rocco, Elena; Martínez-Sáez, Elena; Lois, Sergio; Marín, Oscar; de la Cruz, Xavier; Piscuoglio, Salvatore; Towers, Russel; Vivancos, Ana; Peg, Vicente; Ramon y Cajal, Santiago; Carles, Joan; Rodon, Jordi; González-Cao, María; Tabernero, Josep; Felip, Enriqueta; Sahuquillo, Joan; Berger, Michael F; Cortes, Javier; Reis-Filho, Jorge S; Seoane, Joan

    2015-11-10

    Cell-free circulating tumour DNA (ctDNA) in plasma has been shown to be informative of the genomic alterations present in tumours and has been used to monitor tumour progression and response to treatments. However, patients with brain tumours do not present with or present with low amounts of ctDNA in plasma precluding the genomic characterization of brain cancer through plasma ctDNA. Here we show that ctDNA derived from central nervous system tumours is more abundantly present in the cerebrospinal fluid (CSF) than in plasma. Massively parallel sequencing of CSF ctDNA more comprehensively characterizes the genomic alterations of brain tumours than plasma, allowing the identification of actionable brain tumour somatic mutations. We show that CSF ctDNA levels longitudinally fluctuate in time and follow the changes in brain tumour burden providing biomarkers to monitor brain malignancies. Moreover, CSF ctDNA is shown to facilitate and complement the diagnosis of leptomeningeal carcinomatosis.

  14. Influence of femtosecond laser radiation on cells of the transplantable tumour Krebs-2

    NASA Astrophysics Data System (ADS)

    Meshalkin, Yu P.; Popova, N. A.; Nikolin, V. P.; Kaledin, V. I.; Kirpichnikov, A. V.; Pestryakov, Efim V.

    2012-06-01

    The influence of femtosecond radiation of a titaniumsapphire laser on cells of the transplantable ascitic tumour Krebs-2 was studied. After in vitro irradiation by the pulsed fundamentalharmonic radiation with the wavelength 800 nm, pulse duration 30 fs, repetition rate 1 kHz, mean power 100 and 300 mW and exposure time 3 min, as well as by the second-harmonic radiation (40 nm, 50 fs, 120 mW), all cells were diffusely stained by the vital stain trypan blue, which may be an evidence of their death or abnormalities of membrane permeability. However, implantation of such cells to experimental animals led to formation of tumours at the transplantation site with the kinetics slightly different from the control one. In the group of mice to which the cells were inoculated after irradiation with second harmonic pulses of titanium-sapphire laser the inhibition of tumour growth was observed due to partial death of cells under the action of UV spectral components. To explain the mechanism of the observed phenomenon the possibility of pore formation (photoporation) in the cell membrane, described earlier in the papers on foreign DNA transfection into cells, is considered.

  15. Influence of femtosecond laser radiation on cells of the transplantable tumour Krebs-2

    SciTech Connect

    Meshalkin, Yu P; Popova, N A; Nikolin, V P; Kaledin, V I; Kirpichnikov, A V; Pestryakov, Efim V

    2012-06-30

    The influence of femtosecond radiation of a titaniumsapphire laser on cells of the transplantable ascitic tumour Krebs-2 was studied. After in vitro irradiation by the pulsed fundamentalharmonic radiation with the wavelength 800 nm, pulse duration 30 fs, repetition rate 1 kHz, mean power 100 and 300 mW and exposure time 3 min, as well as by the second-harmonic radiation (40 nm, 50 fs, 120 mW), all cells were diffusely stained by the vital stain trypan blue, which may be an evidence of their death or abnormalities of membrane permeability. However, implantation of such cells to experimental animals led to formation of tumours at the transplantation site with the kinetics slightly different from the control one. In the group of mice to which the cells were inoculated after irradiation with second harmonic pulses of titanium-sapphire laser the inhibition of tumour growth was observed due to partial death of cells under the action of UV spectral components. To explain the mechanism of the observed phenomenon the possibility of pore formation (photoporation) in the cell membrane, described earlier in the papers on foreign DNA transfection into cells, is considered.

  16. Lycobetaine acts as a selective topoisomerase IIβ poison and inhibits the growth of human tumour cells

    PubMed Central

    Barthelmes, H U; Niederberger, E; Roth, T; Schulte, K; Tang, W C; Boege, F; Fiebig, H-H; Eisenbrand, G; Marko, D

    2001-01-01

    The phenanthridine alkaloid lycobetaine is a minor constituent of Amaryllidaceae. Inhibition of cell growth was studied in the clonogenic assay on 21 human tumour xenografts (mean IC 50 = 0.8 μM). The growth of human leukaemia cell lines was also potently inhibited (mean IC 50 = 1.3 μM). Athymic nude mice, carrying s.c. implanted human gastric tumour xenograft GXF251, were treated i.p. with lycobetaine for 4 weeks, resulting in a marked tumour growth delay. Lycobetaine was found to act as a specific topoisomerase IIβ poison. In the presence of calf thymus DNA, pure recombinant human topoisomerase IIβ protein was selectively depleted from SDS-gels, whereas no depletion of topoisomerase IIα protein was observed. In A431 cells immunoband-depletion of topoisomerase IIβ was induced, suggesting stabilization of the covalent catalytic DNA-intermediate in living cells. It is reasonable to assume that this mechanism will cause or at least contribute significantly to the antitumour activity. © 2001 Cancer Research Campaign   http://www.bjcancer.com PMID:11720449

  17. Orbital tumours and tumour-like lesions: exploring the armamentarium of multiparametric imaging.

    PubMed

    Purohit, Bela S; Vargas, Maria Isabel; Ailianou, Angeliki; Merlini, Laura; Poletti, Pierre-Alexandre; Platon, Alexandra; Delattre, Bénédicte M; Rager, Olivier; Burkhardt, Karim; Becker, Minerva

    2016-02-01

    Although the orbit is a small anatomical space, the wide range of structures present within it are often the site of origin of various tumours and tumour-like conditions, both in adults and children. Cross-sectional imaging is mandatory for the detection, characterization, and mapping of these lesions. This review focuses on multiparametric imaging of orbital tumours. Each tumour is reviewed in relation to its clinical presentation, compartmental location, imaging characteristics, and its histological features. We herein describe orbital tumours as lesions of the globe (retinoblastoma, uveal melanoma), optic nerve sheath complex (meningioma, optic nerve glioma), conal-intraconal compartment (hemangioma), extraconal compartment (dermoid/epidermoid, lacrimal gland tumours, lymphoma, rhabdomysarcoma), and bone and sinus compartment (fibrous dysplasia). Lesions without any typical compartmental localization and those with multi-compartment involvement (veno-lymphatic malformation, plexiform neurofibroma, idiopathic orbital pseudotumour, IgG4 related disease, metastases) are also reviewed. We discuss the role of advanced imaging techniques, such as MR diffusion-weighted imaging (DWI), diffusion tensor imaging, fluoro-2-deoxy-D-glucose positron emission tomography CT (FDG-PET CT), and positron emission tomography MRI (MRI PET) as problem-solving tools in the evaluation of those orbital masses that present with non-specific morphologic imaging findings. Main messages/Teaching points • A compartment-based approach is essential for the diagnosis of orbital tumours. • CT and MRI play a key role in the work-up of orbital tumours. • DWI, PET CT, and MRI PET are complementary tools to solve diagnostic dilemmas. • Awareness of salient imaging pearls and diagnostic pitfalls avoids interpretation errors.

  18. Better outcomes by monitoring tumour dynamics using sensitive tumour markers in patients with recurrent gastric cancer.

    PubMed

    Komatsu, Shuhei; Ichikawa, Daisuke; Nishimura, Yukihisa; Kubota, Takeshi; Okamoto, Kazuma; Shiozaki, Atsushi; Fujiwara, Hitoshi; Konishi, Hirotaka; Murayama, Yasutoshi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Otsuji, Eigo

    2013-04-01

    Little is known about the prognostic value and clinical significance of monitoring tumour status using tumour markers in patients with recurrent gastric cancer. Between 2002 and 2009, 91 consecutive patients exhibited recurrence after curative gastrectomy for gastric cancer. They were followed intensively using tumour markers such as CA19-9 and CEA and their records were retrospectively analyzed. At the time of recurrence, patients were divided into three groups. Each tumour marker was re-elevated in 45 patients (51%) (re-elevation group: REG), was continuously-elevated since initial surgery in 23 patients (25%) (continuous elevation group: CEG) and was not elevated in 22 patients (24%) (non-elevation group: NEG). Survival after recurrence in REG was significantly better than in the other groups. In particular, those in REG had significantly better outcomes than those in NEG, in both survival after recurrence (p=0.0109) and total postoperative survival (p=0.0197), although there were no significant differences in recurrence-free survival between the two groups (p=0.8818). REG patients were able to receive more chemotherapy regimens than NEG patients (p=0.0730, REG vs. NEG, first-line 43% vs. 68%, second-line 33% vs. 32%, third-line or more 24% vs. 0%). Multivariate analysis revealed that re-elevations in tumour markers were found to be an independent prognostic factor for survival after recurrence [p=0.0014, hazard ratio=0.39 (95% CI: 0.21-0.69)]. [corrected]. Particularly for peritoneal recurrence, those in REG had significantly better outcomes than those in NEG (p<0.0005). Monitoring tumour dynamics using tumour markers may facilitate clinical decision-making, according to changes in tumour markers and contribute to survival prolongation in patients with recurrent gastric cancer.

  19. Implant-retained nasal prosthesis for reconstruction of large rhinectomy defects: the Salisbury experience.

    PubMed

    Ethunandan, M; Downie, I; Flood, T

    2010-04-01

    The authors report their experience with 34 patients who had large full thickness nasal defects reconstructed with an implant-retained prosthesis. Their technique of modifying post-rhinectomy defects is described and factors influencing implant success are evaluated. 111 implants were placed to retain a nasal prosthesis. Age, sex and tumour histology did not affect the outcome. Smoking, extent of rhinectomy, use of radiotherapy (pre- and post-implant), hyperbaric oxygen, length and location of the implant and type of retention (bar/magnets) influenced implant success. The overall success rate was 89% (99/111); 94% in patients who did not receive radiotherapy and 86% in those who did. The prosthesis was in place in all patients (100%) at the time of last follow up. Post-rhinectomy defect modification enables adequate access for safe placement of long implants with good primary stability and helps the maintenance of good hygiene (further enhanced by the use of skin grafts). The authors think implant-retained prosthesis is a reliable option for reconstructing large full thickness rhinectomy defects. They suggest their technique of modifying the defect, use of long implants and magnets for retention is responsible for the high success rate of implants used to retain a nasal prosthesis.

  20. Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response

    PubMed Central

    Habets, Thomas H. P. M.; Oth, Tammy; Houben, Ans W.; Huijskens, Mirelle J. A. J.; Senden-Gijsbers, Birgit L. M. G.; Schnijderberg, Melanie C. A.; Brans, Boudewijn; Dubois, Ludwig J.; Lambin, Philippe; De Saint-Hubert, Marijke; Germeraad, Wilfred T. V.; Tilanus, Marcel G. J.; Mottaghy, Felix M.

    2016-01-01

    Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects. PMID:27427766

  1. Trends in Cochlear Implants

    PubMed Central

    Zeng, Fan-Gang

    2004-01-01

    More than 60,000 people worldwide use cochlear implants as a means to restore functional hearing. Although individual performance variability is still high, an average implant user can talk on the phone in a quiet environment. Cochlear-implant research has also matured as a field, as evidenced by the exponential growth in both the patient population and scientific publication. The present report examines current issues related to audiologic, clinical, engineering, anatomic, and physiologic aspects of cochlear implants, focusing on their psychophysical, speech, music, and cognitive performance. This report also forecasts clinical and research trends related to presurgical evaluation, fitting protocols, signal processing, and postsurgical rehabilitation in cochlear implants. Finally, a future landscape in amplification is presented that requires a unique, yet complementary, contribution from hearing aids, middle ear implants, and cochlear implants to achieve a total solution to the entire spectrum of hearing loss treatment and management. PMID:15247993

  2. RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary.

    PubMed

    Ryland, Georgina L; Hunter, Sally M; Doyle, Maria A; Rowley, Simone M; Christie, Michael; Allan, Prue E; Bowtell, David D L; Gorringe, Kylie L; Campbell, Ian G

    2013-02-01

    Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under-described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild-type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts.

  3. A chemically modified antibody mediates complete eradication of tumours by selective disruption of tumour blood vessels.

    PubMed

    Palumbo, A; Hauler, F; Dziunycz, P; Schwager, K; Soltermann, A; Pretto, F; Alonso, C; Hofbauer, G F; Boyle, R W; Neri, D

    2011-03-29

    The possibility of eradicating cancer by selective destruction of tumour blood vessels may represent an attractive therapeutic avenue, but most pharmaceutical agents investigated so far did not achieve complete cures and are not completely specific. Antibody conjugates now allow us to evaluate the impact of selective vascular shutdown on tumour viability and to study mechanisms of action. We synthesised a novel porphyrin-based photosensitiser suitable for conjugation to antibodies and assessed anticancer properties of its conjugate with L19, a clinical-stage human monoclonal antibody specific to the alternatively spliced EDB domain of fibronectin, a marker of tumour angiogenesis. Here we show in two mouse model of cancer (F9 and A431) that L19 is capable of highly selective in vivo localisation around tumour blood vessels and that its conjugate with a photosensitiser allows selective disruption of tumour vasculature upon irradiation, leading to complete and long-lasting cancer eradication. Furthermore, depletion experiments revealed that natural killer cells are essential for the induction of long-lasting complete responses. These results reinforce the concept that vascular shutdown can induce a curative avalanche of tumour cell death. Immuno-photodynamic therapy may be particularly indicated for squamous cell carcinoma of the skin, which we show to be strongly positive for markers of angiogenesis.

  4. Soft Tissue Giant Cell Tumour of Low Malignant Potential: A Rare Tumour at a Rare Site

    PubMed Central

    Bhat, Amoolya; V., Geethamani; C., Vijaya

    2013-01-01

    “Soft tissue giant cell tumour of low malignant potential” is considered as the soft tissue counterpart of osteoclastoma of the bone. It is a primary soft tissue tumour which is classified under the category of fibrohistiocytic tumours of intermediate malignancy.Seventy percent of the tumours involve the extremities and only about seven percent of them arise in head and neck region. They are composed of nodules of histiocytes in a vascular stroma, with multinucleated osteoclast-like giant cells positive for vimentin, smooth muscle actin (SMA), CD68 and Tarterate Resistant Acid Phosphatase (TRAP). We are presenting a case of a 75-year-old man who had a nodule on the ala of the nose. Histopathology showed a histiocytic lesion. Benign fibrous histiocytoma, plexiform fibrohistiocytic tumour, solitary reticulohistiocytoma and histioid leprosy were ruled out by using special stains and immunostains. Expression of smooth muscle actin and CD68 confirmed the diagnosis of a soft tissue giant cell tumour with a low malignant potential. PMID:24551690

  5. Identification of novel tumour-associated antigens in canine mammary gland tumour.

    PubMed

    Furuya, M; Funasaki, M; Tani, H; Sasai, K

    2015-09-01

    Canine mammary gland tumour (MGT) is the most common neoplasm in female dogs and has similar biological characteristics to human MGT. Spontaneous canine MGT is a more attractive clinical model in oncological research than that of the murine experimental model. Tumour-associated antigens (TAAs), which are produced in tumour cells, are applied as tumour markers, tumour vaccine antigens and molecular targets of therapeutic drugs. In this study, we have primarily identified 13 different TAAs of canine MGT by serological immunoscreening of cDNA expression library. The results of serological mini-arrays of identified antigens showed that CCDC41 antigen specially reacted with 35% of sera from MGT-dogs and did not react with control sera. We also found that HSPH1 mRNA expression levels increased significantly in MGT tissues. These findings will contribute to the development of diagnostic technologies and translational target therapies for dogs. HSPH1, which is strongly expressed in the tumour tissue, will be a possible vaccine antigen of canine MGT. © 2013 Blackwell Publishing Ltd.

  6. [Phyllodes tumour of the seminal vesicle - case report of a rare tumour entity].

    PubMed

    Rau, D; Alt, W; Kälble, T

    2010-11-01

    Neoplasms of the seminal vesicles are rare. Here we report on a patient with a low-grade phyllodes tumour of the seminal vesicle. The patient was admitted to our hospital with a tumour in the excavatio rectovesicalis diagnosed by CT scan. He had no symptoms. For further diagnosis we took transrectal ultrasound-guided biopsies, the histopathological examination showed no malignant features. One month later a follow-up CT scan demonstrated a significant enlargement of the tumour. Therefore we decided to perform a surgical exploration. During surgery we found a partially necrotic mass involving the prostate, the urinary bladder and the rectum. Both radical cystoprostatectomy with ileal conduit and anterior resection of the rectum with colostomy were necessary. Histologically the specimen showed a low-grade phyllodes tumour of the left seminal vesicle. One year after surgery the follow-up was completely normal without any residual or recurrent tumour. Frequency, histology, diagnostic investigations, therapy and prognosis of this rare tumour entity are discussed with respect to the actual literature.

  7. Stimulation of local solid tumour development of the nonproducer Marek's disease tumour transplant JMV by virus-induced immunosuppression.

    PubMed

    Bulow, V V; Weiland, F

    1980-01-01

    Chickens could be protected against lethal lymphoblastic leukaemia due to the nonproducer JMV Marek's disease (MD) tumour transplant by infection with the herpesvirus of turkeys (HVT) or various strains of MD virus. However, solid JMV tumours developed in MD virus-infected birds at the site of intramuscular or subcutaneous transplantation, but tumours never developed at the site of MD virus inoculation. The incidence and extent of local tumour growth, the development of metastases and the inhibition of tumour regression were related to the pathogenicity of the MD virus strains used for pre-treatment of the chickens. Infection of chickens with reticulo-endotheliosis virus (REV-C) or with chick syncytial virus (CSV), which are nonprotective against MD virus or JMV transplants, stimulated local tumour development of the attenuated JMV-A variant of the JMV transplant. Chickens which did not reject local tumours died of visceral JMV tumour metastases. A direct helper mechanism of viral infection on the oncogenicity of transplants was excluded. The results suggested that virus-induced immunosuppression stimulated the development of local JMV tumours which never occurred in normal chickens. Immunity to the JMV transplant, including resistance to lethal leukaemia and successful regression of local tumours, did not coincide with immunity to MD virus-induced visceral lymphomas or nerve lesions. Vaccinal induced tumour immunity evidently was defective. The significance of these results is discussed with reference to immunological functions of MD tumour-specific antigens.

  8. Treatment of spontaneous tumours by temporary local ligation

    PubMed Central

    Allen, Frederick M.; Kaplan, Martin M.; Meranze, David R.; Gradess, Morton

    1960-01-01

    Previous work in some human cases and in laboratory animals has indicated that temporary local ligation of spontaneous tumours has a selective destructive effect on these tumours, with only temporary inflammation resulting in normal tissues. In the experiments described in this paper, 49 spontaneous accessible tumours in dogs were treated by this method, with periods of ligation of from 4 to 11 hours. Success, as measured by selective necrosis of tumour tissue as compared with normal tissue, was achieved in 29 out of 41 benign tumours, including lipomas, angiomas, adenomas and mixed mammary tumours. Treatment failures were encountered in two cases each of papillomas and fibromas, six mixed mammary tumours and two testicular tumours. Total necrosis of tumour cells occurred in all eight malignant tumours encountered in this series. The outstanding feature was the specific destruction of tumour tissue by a bodily process without participation of any outside agent. Emphasis was placed on an adequate inflammatory response following temporary anoxia, although a precise definition of this inflammation could not be offered. Post-ligation bacterial multiplication, which may be expected to occur in necrotic tumour tissue, is considered to be a secondary effect rather than a possible primary cause of regression and disappearance of the tumour. If ligation treatment can be shown to be successful for a particular type of tumour, it may be possible to apply it to human patients for the treatment of areas not amenable to surgery. The results reported here warrant new experimental approaches to the study of neoplasms at the cellular level to define more precisely the anoxic and inflammatory processes involved in the selective lethal effect on tumour tissues; and the authors suggest that trials should be undertaken of combinations of chemotherapy or irradiation with ligation to reduce ligation time and extend the possible benefits. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7

  9. Synchrotron-based in vivo tracking of implanted mammalian cells.

    PubMed

    Hall, C J; Schültke, E; Rigon, L; Ataelmannan, K; Rigley, S; Menk, R; Arfelli, F; Tromba, G; Pearson, S; Wilkinson, S; Round, A; Crittell, S; Griebel, R; Juurlink, B H J

    2008-12-01

    We have developed an X-ray imaging protocol that permits 3D visualisation of a small number of implanted cells within bulk tissue. The cells are marked using natural endocytosis of inert gold nano-particles. The resulting local increase in electron density allows high imaging contrast to be obtained from small clusters of these marked cells. Using this technique we have imaged C6 glioma cells within the brain of a model animal. The cells were marked by exposing them to colloidal gold incorporated in the growth media. Gold-loaded glioma cells were implanted into the brains of adult male Wistar rats. After tumours had been allowed to develop for up to 2 weeks, the animals were sacrificed and images of the intact cranium were acquired at the SYRMEP imaging station on the Elettra synchrotron in Italy. Computed tomography was performed using mixed absorption and phase contrast techniques at an X-ray energy of 24 keV. In the resulting volume datasets the tumour bulk is clearly visible and the infiltrating nature of the malignant growth is well demonstrated. Although the protocol was developed using this particular model of malignant brain tumour, it is believed that it will be possible to use it with other cell lines.

  10. Immunotherapy of human tumour xenografts overexpressing the EGF receptor with rat antibodies that block growth factor-receptor interaction.

    PubMed Central

    Modjtahedi, H.; Eccles, S.; Box, G.; Styles, J.; Dean, C.

    1993-01-01

    Athymic mice bearing xenografts of human tumours that overexpress the receptor (EGFR) for EGF and TGF alpha have been used to evaluate the therapeutic potential of three new rat monoclonal antibodies (mAbs) directed against two distinct epitopes on the extracellular domain of the human EGFR. The antibodies, ICR16 (IgG2a), ICR62 (IgG2b) and ICR64 (IgG1), have been shown (Modjtahedi et al., 1993) to be potent inhibitors of the growth in vitro of a number of human squamous cell carcinomas because they block receptor-ligand interaction. When given i.p. at 200 micrograms dose, the three antibodies were found to induce complete regression of xenografts of the HN5 tumour if treatment with antibody commenced at the time of tumour implantation (total doses: ICR16, 3.0 mg; ICR62, 1.2 mg; ICR64, 2.2 mg). More importantly when treatment was delayed until the tumours were established (mean diam. 0.5 cm) both ICR16 and ICR62 induced complete or almost complete regression of the tumours. Furthermore, treatment with a total dose of only 0.44 mg of ICR62 was found to induce complete remission of xenografts of the breast carcinoma MDA-MB 468, but ICR16 was less effective at this dose of antibody and only 4/8 tumours regressed completely. ICR16 and ICR62 were poor inhibitors of the growth in vitro of the vulval carcinoma A431, but both induced a substantial delay in the growth of xenografts of this tumour and 4/8 tumours regressed completely in the mice treated with ICR62 (total dose 2.2 mg). Although ICR16 and ICR64 were more effective than ICR62 as growth inhibitors in vitro, ICR62 was found to be substantially better at inducing regression of the tumour xenografts due perhaps to additional activation of host immune effector functions by the IgG2b antibody. We conclude that these antibodies may be useful therapeutic agents that can be used alone without conjugation to other cytotoxic moieties. PMID:7679281

  11. Water-soluble aluminium phthalocyanine–polymer conjugates for PDT: photodynamic activities and pharmacokinetics in tumour-bearing mice

    PubMed Central

    Brasseur, N; Ouellet, R; Madeleine, C La; Lier, J E van

    1999-01-01

    The potential use of unsubstituted aluminium phthalocyanine (AlClPc) as a sensitizer for photodynamic therapy (PDT) of cancer has not been fully exploited in spite of its higher efficiency as compared to the sulphonated derivatives. This is largely due to the strong hydrophobic character of AlClPc which renders the material difficult to formulate for in vivo administration. We prepared two water-soluble derivatives of AlClPc by axial coordination of polyethyleneglycol (PEG, MW 2000) or polyvinylalcohol (PVA, MW 13 000–23 000) to the central aluminium ion. Their photodynamic activities were evaluated in vitro against the EMT-6 mouse mammary tumour cells and in vivo against the EMT-6 and the colon carcinoma Colo-26 tumours implanted intradermally in Balb/c mice. Pharmacokinetics were studied in the EMT-6 tumour-bearing mice. After 1 h incubation, the light dose required to kill 90% of cells (LD90) was at least three times less for AlClPc (Cremophor emulsion) as compared to AlPc–PEG and AlPc–PVA, while after 24 h incubation all three preparations were highly phototoxic. All three dye preparations induced complete EMT-6 tumour regression in 75–100% of animals at a low drug dose (0.25 μmol kg−1) following PDT (400 J cm−2, 650–700 nm) at 24 h pi. Complete tumour regression in the Colo-26 tumour model was obtained in 30% of mice at a dose of 2 μmol kg−1. In the non-cured animals, AlPc–PVA induced the most significant tumour growth delay. This dye showed a prolonged plasma half-life (6.8 h) as compared to AlClPc (2.6 h) and AlPc–PEG (23 min), lower retention by liver and spleen and higher tumour-to-skin and tumour-to-muscle ratios. Our data demonstrate that addition of hydrophilic axial ligands to AlPc, while modifying in vitro and in vivo kinetics, does not reduce the PDT efficiency of the parent molecule. Moreover, in the case of the polyvinylalcohol derivative, axial coordination confers advantageous pharmacokinetics to AlPc, which makes this

  12. Carotid body tumours. A 20-year single-institution experience.

    PubMed

    Dalainas, Ilias; Nano, Giovanni; Casana, Renato; Bianchi, Paolo; Stegher, Silvia; Malacrida, Giovanni; Tealdi, Domenico Giuseppe

    2006-01-01

    The aim of this single-institution retrospective study was to review the surgical outcomes of resection of carotid body tumours over the last 20 years in our hospital. From January 1985 to December 2004, 17 patients were admitted to our institution with carotid body tumours. All patients were treated by surgical resection of the tumour. No perioperative deaths occurred. Perioperative comorbidities were more frequent in patients with large carotid body tumours intimately associated with the carotid vessels. Surgical excision of carotid body tumours is safe and effective even in the long term.

  13. Unravelling mechanisms of p53-mediated tumour suppression

    PubMed Central

    Bieging, Kathryn T.; Mello, Stephano Spano; Attardi, Laura D.

    2014-01-01

    p53 is a crucial tumour suppressor that responds to diverse stress signals by orchestrating specific cellular responses, including transient cell cycle arrest, cellular senescence and apoptosis, which are all processes associated with tumour suppression. However, recent studies have challenged the relative importance of these canonical cellular responses for p53-mediated tumour suppression and