Animal Tumor Research Articles

Novel Human Placenta-Based Extract for Vascularization Strategies in Tissue Engineering.

There is critical unmet need for new vascularized tissues to support or replace injured tissues and organs. Various synthetic and natural materials were already established for use of two-dimensional (2D) and three-dimensional (3D) in vitro neovascularization assays, however, they still cannot mimic the complex functions of the sum of the extracellular matrix (ECM) in native intact tissue. Currently, this issue is only addressed by artificial products such as Matrigel™, which comprises a complex mixture of ECM proteins, extracted from animal tumor tissue. Despite its outstanding bioactivity, the isolation from tumor tissue hinders its translation into clinical applications. Since nonhuman ECM proteins may cause immune reactions, as are frequently observed in clinical trials, human ECM proteins represent the best option when aiming for clinical applications. Here, we describe an effective method of isolating a human placenta substrate (hpS) that induces the spontaneous formation of an interconnected network of green fluorescence-labeled human umbilical vein endothelial cells (gfpHUVECs) in vitro. The substrate was biochemically characterized by using a combination of bicinchoninic acid (BCA) assay, DNA, and glycosaminoglycan (GAG) content assays, sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis and Western blot, angiogenesis arrays, chromatographic thrombin detection, high performance liquid chromatography (HPLC)-based amino acid quantification analysis, and assessment of antimicrobial properties. 2D in vitro cell culture experiments have been performed to determine the vasculogenic potential of hpS, which demonstrated that cell networks developed on hpS show a significantly higher degree of complexity (number of tubules/junctions; total/mean tube length) when compared with Matrigel. As 3D cell culture techniques represent a more accurate representation of the in vivo condition, the substrate was 3D solidified using various natural polymers. 3D in vitro vasculogenesis assays have been performed by seeding gfpHUVECs in an hpS-fibrinogen clot. In conclusion, hpS provides a potent human/material-based alternative to xenogenic-material-based biomaterials for vascularization strategies in tissue engineering.

A Phase 1-2 Trial of Concurrent Radiation Therapy, Cisplatin and BMX-001 in Locally Advanced Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Prevention/mitigation of oral mucositis (OM) and xerostomia are challenges to the use of chemoradiation (CRT) for advanced head and neck squamous ca (HNSCC). MnTnBuOE-2-PyP5⁺(BMX-001) is a lipophilic manganese metalloporphyrin superoxide dismutase mimic that protects against radiation and chemotherapy induced OM in orthotopic animal tumor models. This study objective was to determine the toxicity profile of BMX-001 given during CRT for locally advanced HNSCC and to measure the incidence of severe (CTCAE v 4.03 grade 3-4) OM and xerostomia. <h3>Materials/Methods</h3> Multi-center prospective phase 1-2 open label trial for patients with AJCC 7 stage III/IVB HNSCC undergoing concurrent RT/cisplatin, curative (70 Gy) or post-op (60-66 Gy). BMX-001 was administered subcutaneously 2x/week during CRT with an initial loading dose given up to 4 days prior to the start of CRT. Two additional doses of BMX-001 were given in the first week post-CRT. A 3+3 design was used. BMX-001 dose levels were 1: 7 mg load/3.5 mg maintenance; 2: 14 mg load/ 7mg maintenance; 3: 28 mg load/ 14 mg maintenance. Level 3 was expanded to assess phase 2 endpoints. Co-primary endpoints: toxicity of BMX-001 and the incidence of severe (grade 3-4) OM. OM was evaluated 2x/week during CRT and then weekly for 4 additional weeks. Secondary endpoints: median duration and time to onset of grade 3-4 OM, grade ≥2 xerostomia 1- and 6-months post-CRT, and progression-free survival (PFS). <h3>Results</h3> A total of 29 patients (M:F = 25:4) were enrolled from 5/2017-12/2019. Primary sites: p16+ oropharynx 25 (86%), nasopharynx (1), hard palate (1), unknown primary (2). Median age: 62 yo (IQR:56-67). Dose levels were 1 (3); 2 (3); dose 3 (23). Median RT dose: 70 Gy (IQR 70-70). 79.3% of subjects received > 200mg/m² of CDDP. All subjects on levels 1 and 2 received all BMX-001 as prescribed by protocol. Level 3, 19/23 (83%) received all doses of BMX-001. All patients had a grade 1 injection site reaction. There were 2 (7%) mild AEs related to QT interval prolongation and 3 serious adverse events (SAE) categorized as possibly related to BMX-001: hypotension, fever with pancytopenia, and hyponatremia. Other SAEs (n = 19) were judged to be expected due to the nature of the disease or treatment with CRT. Incidence of severe OM was 41% (median duration 25 days, IQR 25-47). Median time to onset of severe OM was 43 (IQR 34-52) days; 83.3% cases of severe OM resolved by 5 weeks post-CRT. Incidence of grade ≥ 2 xerostomia was 18%, 8%, and 9% at 1, 6, and 12 months respectively post-CRT. Mean unstimulated whole saliva production was 0.69 ml/min at baseline and 0.29 ml/min at 1 yr. Mean stimulated whole saliva production was 1.38 ml/min at baseline and 0.72ml/min at 1 yr. Median follow up was 20 mo. 1 yr PFS was 96.6%. <h3>Conclusion</h3> CRT and 2x/week BMX-001 was safe in HNSCC at the highest dose tested. Promising rates of severe OM and xerostomia justify further investigation in HNSCC patients receiving CRT.

A text-mining based analysis of 100,000 tumours affecting dogs and cats in the United Kingdom

Cancer is a major reason for veterinary consultation, especially in companion animals. Cancer surveillance plays a key role in prevention but opportunities for such surveillance in companion animals are limited by the lack of suitable veterinary population health infrastructures. In this paper we describe a pathology-based animal tumour registry (PTR) developed within the Small Animal Veterinary Surveillance Network (SAVSNET) built from electronic pathology records (EPR) submitted to this network. From an original collection of 180232 free text (non-structured) EPRs reported between April 2018 and June 2019, we used specific text-mining methodologies to identify 109895 neoplasias. These data were normalized to describe both the tumour (type and location) and the animal (breed, neutering status and veterinary practice postcode). The resulting PTR, the largest of its kind for companion animals to date, is an important research resource being able to facilitate a wide array of research in areas including surveillance, clinical decision making and comparative cancer biology.

Inhibition of BIRC2 Sensitizes α7-HPV-Related Cervical Squamous Cell Carcinoma to Chemotherapy.

The α7-human papillomavirus (HPV)-related cervical squamous cell carcinoma (SCC) is associated with poor prognosis. We compared the genomic profiles of this disease in a cohort corresponding to the 2001–2014 period with various responses to radiotherapy or concurrent chemoradiation through microRNA (miR) profiling involving miR 4.0 array and human transcriptome array 2.0 analyses. A real-time quantitative polymerase chain reaction was then conducted to identify the predictive biomarkers. A significantly lower expression of miR143-3p in recurrent tumors (p = 0.0309) relative to that in nonrecurrent tumors was observed. The miR143-3p targeted the mRNA expression of the baculoviral inhibitor of the apoptosis protein (IAP) repeat-containing 2 (BIRC2; p = 0.0261). The BIRC2 protein levels (p = 0.0023) were significantly higher in recurrent tumors than in nonrecurrent tumors. Moreover, the miR-143-3p sensitized the response of α7-HPV-related cervical SCC to chemotherapy by targeting BIRC2. A combination of BIRC2-inhibitor LCL161 and topotecan exerted synergistic effects on cancer cells and animal tumor models. In a pooled cohort of α7-HPV-related cervical SCC (including mixed infections with non-α7-HPV) treated between 1993 and 2014, high BIRC2 expression was associated with significantly worse outcomes (cancer-specific survival, hazard ratio (HR) = 1.42, p = 0.008; progression-free survival, HR = 1.64; p = 0.005). Summarily, BIRC2 constitutes a novel prognostic factor and therapeutic target for α7-HPV-related cervical SCC.

A Computational Study on Magnetic Nanoparticles Hyperthermia of Ellipsoidal Tumors

The modelling of magnetic hyperthermia using nanoparticles of ellipsoid tumor shapes has not been studied adequately. To fill this gap, a computational study has been carried out to determine two key treatment parameters: the therapeutic temperature distribution and the extent of thermal damage. Prolate and oblate spheroidal tumors, of various aspect ratios, surrounded by a large healthy tissue region are assumed. Tissue temperatures are determined from the solution of Pennes’ bio-heat transfer equation. The mortality of the tissues is determined by the Arrhenius kinetic model. The computational model is successfully verified against a closed-form solution for a perfectly spherical tumor. The therapeutic temperature and the thermal damage in the tumor center decrease as the aspect ratio increases and it is insensitive to whether tumors of the same aspect ratio are oblate or prolate spheroids. The necrotic tumor area is affected by the tumor prolateness and oblateness. Good comparison is obtained of the present model with three sets of experimental measurements taken from the literature, for animal tumors exhibiting ellipsoid-like geometry. The computational model enables the determination of the therapeutic temperature and tissue thermal damage for magnetic hyperthermia of ellipsoidal tumors. It can be easily reproduced for various treatment scenarios and may be useful for an effective treatment planning of ellipsoidal tumor geometries.

Positive electrostatic therapy of metastatic tumors: selective induction of apoptosis in cancer cells by pure charges.

BackgroundWe discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues.MethodsWe interacted normal and cancer cell lines and animal tumors with PECs by connecting a charged patch to cancer cells and animal tumors. many biochemical, molecular and radiological assays were carried out on PEC treated and control samples.ResultsCorrelative interactions between electrostatic charges and cancer cells contain critical unknown factors that influence cancer diagnosis and treatment. Different types of cell analyses prove PEC‐based apoptosis induction in malignant cell lines. Flowcytometry and viability assay depict selective destructive effects of PEC on malignant breast cancer cells. Additionally, strong patterns of pyknotic apoptosis, as well as downregulation of proliferative‐associated proteins (Ki67, CD31, and HIF‐1α), were observed in histopathological and immunohistochemical patterns of treated mouse malignant tumors, respectively. Quantitative real‐time polymerase chain reaction results demonstrate up/down‐regulated apoptotic/proliferative transcriptomes (P21, P27, P53/CD34, integrin α5, vascular endothelial growth factor, and vascular endothelial growth factor receptor) in treated animal tumors. Expression of propidium iodide in confocal microscopy images of treated malignant tissues was another indication of the destructive effects of PECs on such cells. Significant tumor size reduction and prognosis improvement were seen in over 95% of treated mouse models with no adverse effects on normal tissues.ConclusionWe discovered that pure positive electrostatic charges (PECs) have an intrinsic suppressive effect on the proliferation and metabolism of invasive cancer cells (cell lines and animal models) without affecting normal tissues. The findings were statistically and observationally significant when compared to radio/chemotherapy‐treated mouse models. As a result, this nonionizing radiation may be used as a practical complementary approach with no discernible side effects after passing future human model studies.

Metastatic and non-metastatic melanoma imaging using Sgc8-c aptamer PTK7-recognizer

Melanoma is one of the most aggressive and deadly skin cancers, and although histopathological criteria are used for its prognosis, biomarkers are necessary to identify the different evolution stages. The applications of molecular imaging include the in vivo diagnosis of cancer with probes that recognize the tumor-biomarkers specific expression allowing external image acquisitions and evaluation of the biological process in quali-quantitative ways. Aptamers are oligonucleotides that recognize targets with high affinity and specificity presenting advantages that make them interesting molecular imaging probes. Sgc8-c (DNA-aptamer) selectively recognizes PTK7-receptor overexpressed in various types of tumors. Herein, Sgc8-c was evaluated, for the first time, in a metastatic melanoma model as molecular imaging probe for in vivo diagnostic, as well as in a non-metastatic melanoma model. Firstly, two probes, radio- and fluorescent-probe, were in vitro evaluated verifying the high specific PTK7 recognition and its internalization in tumor cells by the endosomal route. Secondly, in vivo proof of concept was performed in animal tumor models. In addition, they have rapid clearance from blood exhibiting excellent target (tumor)/non-target organ ratios. Furthermore, optimal biodistribution was observed 24 h after probes injections accumulating almost exclusively in the tumor tissue. Sgc8-c is a potential tool for their specific use in the early detection of melanoma.

Sonodynamic therapy complements PD-L1 immune checkpoint inhibition in a murine model of pancreatic cancer.

The emergence of immune checkpoint inhibitors (ICI's) in the past decade has proven transformative in the area of immuno-oncology. The PD-1/PD-L1 axis has been particularly well studied and monoclonal antibodies developed to block either the receptor (anti PD-1) or its associated ligand (anti PD-L1) can generate potent anti-tumour immunity in certain tumour models. However, many "immune cold" tumours remain unresponsive to ICI's and strategies to stimulate the adaptive immune system and make these tumours more susceptible to ICI treatment are currently under investigation. Sonodynamic therapy (SDT) is a targeted anti-cancer treatment that uses ultrasound to activate a sensitiser with the resulting generation of reactive oxygen species (ROS) causing direct cell death by apoptosis and necrosis. SDT has also been shown to stimulate the adaptive immune system in a pre-clinical model of colorectal cancer. In this manuscript, we investigate the ability of microbubble mediated SDT to control tumour growth in a bilateral tumour mouse model of pancreatic cancer by treating the target tumour with SDT and observing the effects at the off-target untreated tumour. The results demonstrated a significant 287% decrease in tumour volume when compared to untreated animals 11 days following the initial treatment with SDT, which reduced further to 369% when SDT was combined with anti-PD-L1 ICI treatment. Analysis of residual tumour tissues remaining after treatment revealed increased levels of infiltrating CD4+ and CD8+ T-lymphocytes (respectively 4.65 and 3.16-fold more) in the off-target tumours of animals where the target tumour was treated with SDT and anti-PD-L1, when compared to untreated tumours. These results suggest that SDT treatment elicits an adaptive immune response that is potentiated by the anti-PD-L1 ICI in this particular model of pancreatic cancer.

The Impact of Sequencing Human Genome on Cancer Chemotherapy

This abstract describes the rational development of novel drugs design for treating cancers based on the information provided by the sequencing of Human Genome. Out of 24,000 genes in our Genome, sixteen thousand genes code for good proteins that keep us healthy. Six thousand mutated genes are identified which are responsible for causing six thousand different diseases including cancers. The most obvious approach is to design drugs to shut off mutated genes that code for wrong protein. Professor Ross was the first person to use a highly toxic chemical called Nitrogen Mustard developed during the World Wars to shut off a cancer-causing gene. Nitrogen Mustard can cross-link double stranded DNA and shut off a gene. Unfortunately, it has no selectivity. It cross-links all rapidly dividing cells both normal and abnormal cells. This abstract also describes the use of a novel class of drugs called Aziridines which acts as a Prodrug. It does not attack all dividing cells, Aziridines are activated in the presence of acid. As cancer cells grow rapidly, they use Glucose as a source of energy. In cancer cells, Glucose is broken down to produce Lactic Acid. It is the acid that activate Aziridine ring which opens to attack a single strand of DNA shutting off the genes. Over the years, we developed over a hundred analogs of Aziridines and tested against an experimental animal tumor called the Walker Carcinoma 256 in Rats. One compound, Aziridine dinitro-benzamide (CB1854) is found to be seventy times more toxic to cancer cell. Using the same rationale, we translated animal work in human making AZQ (US Patent 4,146,622 &amp; 4,233,215) for treating Glioblastoma, a solid aggressive brain tumor in human. A new approach to treat Breast Cancer is also described.

3-Epipachysamine B suppresses proliferation and induces apoptosis of breast cancer cell via PI3K/AKT/mTOR signaling pathway

3-Epipachysamine B is a natural steroidal alkaloid isolated from Pachysandra terminalis Sieb. et Zucc. (known locally as Kunxianqi). Kunxianqi contains numerous compounds with demonstrated activity against breast cancer (BRCA). However, it is unknown whether 3-epipachysamine B also has anti-BRCA efficacy. In the present study, we employed network pharmacology technology to search and find potential molecular targets of 3-epipachysamine B. We applied cell proliferation, apoptosis, and western blotting assays to test the predicted key targets and the effects of 3-epipachysamine B against BRCA. Network pharmacology disclosed 80 potential BRCA-related targets of 3-epipachysamine B and assigned them to 75 signaling pathways. Of these, the most highly enriched was the PI3K/AKT signaling pathway. PIK3R1, AKT1, and mTOR had high degrees and betweenness centrality in protein-protein interaction network and are associated with PI3K/AKT signaling. Molecular docking and molecular dynamics simulation indicated strong binding between 3-epipachysamine B and PIK3R1, AKT1, and mTOR. 3-Epipachysamine B repressed the proliferation and induced the apoptosis of BRCA cells, as well as downregulated P-AKT/AKT, P-mTOR/mTOR, and P-PI3K/PI3K in the cells. The PI3K inhibitor LY294002 augmented these changes. Hence, 3-epipachysamine could also prove effective as an anticancer agent in future animal tumor model and human clinical breast cancer trials. Successful validation results could lead to a safe and effective new breast cancer treatment that improves patient prognosis and quality of life.

Therapeutic Modification of Hypoxia

Regions of reduced oxygenation (hypoxia) are a characteristic feature of virtually all animal and human solid tumours. Numerous preclinical studies, both in vitro and in vivo, have shown that decreasing oxygen concentration induces resistance to radiation. Importantly, hypoxia in human tumours is a negative indicator of radiotherapy outcome. Hypoxia also contributes to resistance to other cancer therapeutics, including immunotherapy, and increases malignant progression as well as cancer cell dissemination. Consequently, substantial effort has been made to detect hypoxia in human tumours and identify realistic approaches to overcome hypoxia and improve cancer therapy outcomes. Hypoxia-targeting strategies include improving oxygen availability, sensitising hypoxic cells to radiation, preferentially killing these cells, locating the hypoxic regions in tumours and increasing the radiation dose to those areas, or applying high energy transfer radiation, which is less affected by hypoxia. Despite numerous clinical studies with each of these hypoxia-modifying approaches, many of which improved both local tumour control and overall survival, hypoxic modification has not been established in routine clinical practice. Here we review the background and significance of hypoxia, how it can be imaged clinically and focus on the various hypoxia-modifying techniques that have undergone, or are currently in, clinical evaluation.

Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis.

Simple SummaryThis review focuses on the pro-tumorigenic action of neutrophil extracellular traps (NETs). NETs were found in various samples of human and animal tumors. The role of the NETs in tumor development increasingly includes cancer immunoediting and interactions between immune system and cancer cells. NETs awake dormant cancer cells, play a key regulatory role in the tumor microenvironment, and exacerbate tumor aggressiveness by enhancing cancer migration and invasion capacity. Furthermore, NETs induce the epithelial to mesenchymal transition in tumor cells. NET proteinases can also degrade the extracellular matrix, promoting cancer cell extravasation. Moreover, NETs can entrap circulating cancer cells and, in that way, facilitate metastasis. A better understanding of the crosstalk between cancer and NETs can help to devise novel approaches to the therapeutic interventions that block cancer evasion mechanisms and prevent metastatic spread.The present review highlights the complex interactions between cancer and neutrophil extracellular traps (NETs). Neutrophils constitute the first line of defense against foreign invaders using major effector mechanisms: phagocytosis, degranulation, and NETs formation. NETs are composed from decondensed nuclear or mitochondrial DNA decorated with proteases and various inflammatory mediators. Although NETs play a crucial role in defense against systemic infections, they also participate in non-infectious conditions, such as inflammation, autoimmune disorders, and cancer. Cancer cells recruit neutrophils (tumor-associated neutrophils, TANs), releasing NETs to the tumor microenvironment. NETs were found in various samples of human and animal tumors, such as pancreatic, breast, liver, and gastric cancers and around metastatic tumors. The role of the NETs in tumor development increasingly includes cancer immunoediting and interactions between the immune system and cancer cells. According to the accumulated evidence, NETs awake dormant cancer cells, causing tumor relapse, as well as its unconstrained growth and spread. NETs play a key regulatory role in the tumor microenvironment, such as the development of distant metastases through the secretion of proteases, i.e., matrix metalloproteinases and proinflammatory cytokines. NETs, furthermore, directly exacerbate tumor aggressiveness by enhancing cancer migration and invasion capacity. The collected evidence also states that through the induction of the high-mobility group box 1, NETs induce the epithelial to mesenchymal transition in tumor cells and, thereby, potentiate their invasiveness. NET proteinases can also degrade the extracellular matrix, promoting cancer cell extravasation. Moreover, NETs can entrap circulating cancer cells and, in that way, facilitate metastasis. NETs directly trigger tumor cell proliferation through their proteases or activating signals. This review focused on the pro-tumorigenic action of NETs, in spite of its potential to also exhibit an antitumor effect. NET components, such as myeloperoxidase or histones, have been shown to directly kill cancer cells. A better understanding of the crosstalk between cancer and NETs can help to devise novel approaches to the therapeutic interventions that block cancer evasion mechanisms and prevent metastatic spread. This review sought to provide the most recent knowledge on the crosstalk between NETs and cancer, and bring more profound ideas for future scientists exploring this field.

ПАТОМОРФОЛОГИЧЕСКИЕ ИЗМЕНЕНИЯ В ОРГАНАХ КОШКИ ПРИ АДЕНОКАРЦЕНОМЕ

Oncological diseases of unproductive animals are becoming increasingly common in veterinary practice, especially in large cities. The basis of tumor growth is the unlimited uncontrolled reproduction of cells by the body, which leads to a complex of structural and functional disorders. Despite the significant achievements of modern veterinary medicine in the field of diagnosis of benign and malignant tumors in animals, the issues of histological and cytological diagnosis of the forms of manifestation of this pathology remain problematic. Long-term statistical data show that there is a tendency to increase the incidence of oncological pathology in domestic carnivores, especially in the malignant form.

Experimental evaluation of targeting accuracy of ultrasound imaging-guided robotic HIFU ablative system for the treatment of solid tumors in pre-clinical studies

We have designed and built low-cost compact ultrasound imaging-guided robotic HIFU (High-Intensity Focused Ultrasound) ablation device for thermal damage of solid tumors in small animals. Before this device is used to treat animals, experimental studies on ex vivo tissues were necessary to assess the accuracy of its targeting, ensuring the safety of therapy. The objective of this study was to assess the targeting accuracy of our device in the focal and axial plane of the HIFU beam using ex vivo tissue embedded in a reference cylindrical chamber inside which a coaxial cylindrical volume with a smaller diameter was ablated. HIFU beams with selected acoustic parameters, generated by a singe-element bowl-shaped 64-mm HIFU transducer operating at 1.08 MHz or 3.21 MHz frequency, were propagated in two-layer media: water-tissue (50 mm-40 mm) and focused at 12.6-mm depth below the tissue surface. Cylindrical necrotic lesions of various size were created by moving the chamber using a computer-controlled precise positioning unit. Lesions formed were compared with those intended for treatment using various visualization methods and displacement between their centers were determined. The targeting accuracy in the focal and axial planes was found to be respectively about 98% and 86% when determined from photos and about 88% and 76% when determined from MR images. The displacement between the centers of the necrotic lesion formed and planned for treatment was about 1 mm in the focal plane and about 2 mm in the axial plane. Our ablation device can be used as an effective and safe tool to plan, monitor and treat solid tumors in small animals and to test new anti-cancer drugs in preclinical studies.

Viscum album (L) extracts in cancer treatment: a systematic review of in vitro and in vivo studies

Background: Several reviews about phytotherapy and homeopathy have been published in the last years, including Viscum album (VA.L). VA is a parasite plant whose extract has anti-cancer proprieties and is used alone or in combination with conventional chemotherapy. &#x0D; Methods: We performed a systematic review about the in vivo and in vitro models described in the literature, including veterinary clinical trials. The literature was consulted from Pubmed database.&#x0D; Results: There are several kinds of pharmaceutical preparations about VA and their active principles used in experimental studies, lectin being frequently studied (alone or as an extract compound). More than 50% of available literature about VA is related to the lectin effects. On the other hand, the effects of viscotoxins are less studied. Among the in vivo experimental studies about VA and its compounds, the B16 murine melanoma is the most used model, followed by Ehrlich, Walker and Dalton tumors. The results point to the apoptotic effects, metastasis control and tumor regression. Some veterinary clinical studies about the use of VA in the treatment of sarcoid, fibrosarcoma and neuroblastoma are quoted in literature too, with interesting results. Considering the in vitro models, our review revealed that NALM6 leukemia cells, B16 melanoma and NC1-H460 lung carcinoma were the most studied tumor models, apoptosis signals being the most important findings. Only one study verified immunoglobulin and interleukin production. All consulted papers were related to phytotherapy preparations only.&#x0D; Conclusions: Although the literature about the anti-cancer activity of VA extract and its lectins is enough, there is a marked lack of information about viscotoxin activities and about the effects of homeopathic preparations of this plant on animal tumors and on in vitro cultivated tumor cells.

Use of X-Ray Fluorescence Microscopy for Studies on Research Models of Hepatocellular Carcinoma.

Introduction: TheraSphere® microspheres containing yttrium 90Y are among many radioembolization agents used clinically to reduce liver tumor burden, and their effects on cancer volume reduction are well-established. At the same time, concerns about off target tissue injury often limit their use. Deeper investigation into tissue distribution and long-term impact of these microspheres could inform us about additional ways to use them in practice.Methods: Healthy rat liver and rabbit liver tumor samples from animals treated with TheraSpheres were sectioned and their elemental maps were generated by X-ray fluorescence microscopy (XFM) at the Advanced Photon Source (APS) synchrotron at Argonne National Laboratory (ANL).Results: Elemental imaging allowed us to identify the presence and distribution of TheraSpheres in animal tissues without the need for additional sample manipulation or staining. Ionizing radiation produced by 90Y radioactive contaminants present in these microspheres makes processing TheraSphere treated samples complex. Accumulation of microspheres in macrophages was observed.Conclusions: This is the first study that used XFM to evaluate the location of microspheres and radionuclides in animal liver and tumor samples introduced through radioembolization. XFM has shown promise in expanding our understanding of radioembolization and could be used for investigation of human patient samples in the future.

Radioactive Beams for Image-Guided Particle Therapy: The BARB Experiment at GSI.

Several techniques are under development for image-guidance in particle therapy. Positron (β+) emission tomography (PET) is in use since many years, because accelerated ions generate positron-emitting isotopes by nuclear fragmentation in the human body. In heavy ion therapy, a major part of the PET signals is produced by β+-emitters generated via projectile fragmentation. A much higher intensity for the PET signal can be obtained using β+-radioactive beams directly for treatment. This idea has always been hampered by the low intensity of the secondary beams, produced by fragmentation of the primary, stable beams. With the intensity upgrade of the SIS-18 synchrotron and the isotopic separation with the fragment separator FRS in the FAIR-phase-0 in Darmstadt, it is now possible to reach radioactive ion beams with sufficient intensity to treat a tumor in small animals. This was the motivation of the BARB (Biomedical Applications of Radioactive ion Beams) experiment that is ongoing at GSI in Darmstadt. This paper will present the plans and instruments developed by the BARB collaboration for testing the use of radioactive beams in cancer therapy.

Photoacoustic computed tomography of mechanical HIFU-induced vascular injury.

Mechanical high-intensity focused ultrasound (HIFU) has been used for cancer treatment and drug delivery. Existing monitoring methods for mechanical HIFU therapies such as MRI and ultrasound imaging often suffer from high cost, poor spatial-temporal resolution, and/or low sensitivity to tissue's hemodynamic changes. Evaluating vascular injury during mechanical HIFU treatment, therefore, remains challenging. Photoacoustic computed tomography (PACT) is a promising tool to meet this need. Intrinsically sensitive to optical absorption, PACT provides high-resolution imaging of blood vessels using hemoglobin as the endogenous contrast. In this study, we have developed an integrated HIFU-PACT system for detecting vascular rupture in mechanical HIFU treatment. We have demonstrated singular value decomposition for enhancing hemorrhage detection. We have validated the HIFU-PACT performance on phantoms and in vivo animal tumor models. We expect that PACT-HIFU will find practical applications in oncology research using small animal models.

What is your diagnosis? Fine-needle aspirate biopsy from a skin mass on the distal metatarsus of a dog.

What is your diagnosis? Fine-needle aspirate biopsy from a skin mass on the distal metatarsus of a dog.

Clinical, Radiological and Microscopical Findings of Chondrosarcoma in a Cat

Chondrosarcoma is an uncommon malignant neoplasm in which the neoplastic cells produce chondroid and varying amounts of matrix. This tumor is the second most common primary skeletal tumor in animal. In this case, radiological and histopathological findings supported a final diagnosis of chondrosarcoma in a cat. A six-year-old male cat weighing 6.3 kg with a large and solitary mass in the right humerus was referred. The shoulder joint had a limited range of motion. Radiographs were obtained from the raised growth. The mass was surgically excised for histopathological evaluation. Microscopically, the mass was composed of bundles and nests of neoplastic mesenchymal cells. Histopathologically, multiple sized of lacunae within a homogenous cartilage matrix were observed. There was marked anisocytosis and anisokaryosis. Neoplastic chondrocytes and pleomorphic to oval cells with 1 to 3 nucleoli were seen. Based on the macroscopical, radiological and the cartilaginous differentiation of tumor cells and matrix, the mass was diagnosed well differentiated chondrosarcoma.