Electrochemotherapy, a combination of high voltage electric pulses and of an anticancer drug, has been demonstrated to be highly effective in treatment of cutaneous and subcutaneous tumors. Unique ...properties of electrochemotherapy (e.g., high specificity for targeting cancer cells, high degree of localization of treatment effect, capacity for preserving the innate immune response and the structure of the extracellular matrix) are facilitating its wide spread in the clinics. Due to high effectiveness of electrochemotherapy in treatment of cutaneous and subcutaneous tumors regardless of histological origin, there are now attempts to extend its use to treatment of internal tumors. To advance the applicability of electrochemotherapy to treatment of internal solid tumors, new technological developments are needed that will enable treatment of these tumors in daily clinical practice. New electrodes through which electric pulses are delivered to target tissue need to be designed with the aim to access target tissue anywhere in the body. To increase the probability of complete tumor eradication, the electrodes have to be accurately positioned, first to provide an adequate extent of electroporation of all tumor cells and second not to damage critical healthy tissue or organs in its vicinity. This can be achieved by image guided insertion of electrodes that will enable accurate positioning of the electrodes in combination with patient-specific numerical treatment planning or using a predefined geometry of electrodes. In order to be able to use electrochemotherapy safely for treatment of internal tumors located in relative proximity of the heart (e.g., in case of liver metastases), the treatment must be performed without interfering with the heart’s electrical activity. We describe recent technological advances, which allow treatment of liver and bone metastases, soft tissue sarcomas, brain tumors, and colorectal and esophageal tumors. The first clinical experiences in these novel application areas of electrochemotherapy are also described.
Fiber reinforced polymer composites are an extremely broad and versatile class of material.Their high strength coupled with lightweight leads to their use wherever structural efficiency is at a ...premium. Applications can be found in aircraft, process plants, sporting goods and military equipment. However they are heterogeneous in construction and antisotropic, which makes making strength prediction extremely difficult especially compared to that of a metal. This book brings together the results of a 12year worldwide failure exercise encompassing 19 theories in a single volume. Each contributor describes their own theory and employs it to solve 14 challenging problems. The accuracy of predictions and the performance of the theories are assessed and recommendations made on the uses of the theories in engineering design.All the necessary information is provided for the methodology to be readily employed for validating and benchmarking new theories as they emerge.Brings together 19 failure theories, with many application examples. Compares the leading failure theories with one another and with experimental data Failure to apply these theories could result in potentially unsafe designs or over design.
Basal cell carcinoma (BCC) are the commonest cutaneous malignancy and incidence continues to increase. There is a need to expand the therapeutic toolbox to increase options for patients that are ...unsuitable for or unwilling to undergo the current therapies.
Electrochemotherapy (ECT) is a technique where cells are temporarily permeabilized after exposure to a brief pulsed electrical field and combined with low dose chemotherapeutics to ablate malignancies. It is a simple technique causing minimal damage to the surrounding healthy tissue and has the potential to avoid the need for complex reconstruction. ECT is an established treatment for skin metastases but its role as a primary treatment modality is not demonstrated.
A prospective randomised control trial evaluating ECT against the gold standard of treatment, Surgery, was performed for patients with primary BCC and patients followed for 5 years. All lesions treated with ECT (n = 69) responded although 8/69 (12%) needed a second treatment to ensure a complete response. All surgical lesions (n = 48) showed histological evidence of complete excision with 2/48 (4%) undergoing a second excision. At 5 years, in the surgical arm there was no evidence of recurrence in 39/40 (97.5%) lesions with 1/40 (2.5%) confirmed recurrence. In the ECT arm there was no evidence of recurrence in 42/48 lesions (87.5%). There was 5 confirmed recurrences. These groups show statistical equivalence in this non inferiority study design (p = 0.33).
ECT is an effective and durable treatment option for primary BCC and should be considered as part of the armamentarium of options available.
Electroporation in veterinary oncology Impellizeri, J.; Aurisicchio, L.; Forde, P. ...
The veterinary journal (1997),
November 2016, 2016-Nov, 2016-11-00, 20161101, Volume:
217
Journal Article
Peer reviewed
•Electrochemotherapy is an emerging treatment for cancer.•Electroporation opens cell membranes, allowing therapeutic substances to enter cells.•Electrochemotherapy is used for local tumour control ...and is increasingly being used to deliver immunotherapy.•Electroporation will become a standard therapeutic option for treating cancer in veterinary medicine.
Cancer treatments in veterinary medicine continue to evolve beyond the established standard therapies of surgery, chemotherapy and radiation therapy. New technologies in cancer therapy include a targeted mechanism to open the cell membrane based on electroporation, driving therapeutic agents, such as chemotherapy (electro-chemotherapy), for local control of cancer, or delivery of gene-based products (electro-gene therapy), directly into the cancer cell to achieve systemic control. This review examines electrochemotherapy and electro-gene therapy in veterinary medicine and considers future directions and applications.
Four laccase isozyme genes, Psc lac1, 2, 3 and 4 have been cloned from the edible mushroom, Pleurotus sajor-caju. The genes display a high degree of homology with other basidiomycete laccases ...(55-99%) at the amino acid level. Of the laccase genes isolated, Psc lac1 and 4 displayed the highest degree of similarity (85% at the amino acid level), while Psc lac3 showed the highest degree of divergence, exhibiting only 52-57% amino acid similarity to the other PL: sajor-caju laccase gene sequences. Laccase activity in PL: sajor-caju is affected by nutrient nitrogen and carbon, and by the addition of copper and manganese to the growth medium. In addition, 2,5-xylidine, ferulic acid, veratric acid and 1-hydroxybenzotriazole induced laccase activity in the fungus. Induction of individual laccase isozyme genes by carbon, nitrogen, copper, manganese and the two aromatic compounds, 2,5-xylidine and ferulic acid, occurred at the level of gene transcription. While Psc lac3 transcript levels appeared to be constitutively expressed, transcript levels for the other laccase isozyme genes, lac1, 2 and 4, were differentially regulated under the conditions tested.
The World-Wide Failure Exercise (WWFE) contained a detailed assessment of 19 theoretical approaches for predicting the deformation and failure response of polymer composite laminates when subjected ...to complex states of stress. The leading five theories are explored in greater detail to demonstrate their strengths and weaknesses in predicting various types of structural failure. Recommendations are then derived, as to how the theories can be best utilised to provide safe and economic predictions in a wide range of engineering design applications. Further guidance is provided for designers on the level of confidence and bounds of applicability of the current theories. The need for careful interpretation of initial failure predictions is emphasised, as is the need to allow for multiple sources of non-linearity (including progressive damage) where accuracy is sought for certain classes of large deformation and final failure strength predictions. Aspects requiring further experimental and theoretical investigation are identified. Direction is also provided to the research community by highlighting specific, tightly focussed, experimental and theoretical studies that, if carried out in the very near future, would pay great dividends from the designer's perspective, by increasing their confidence in the theoretical foundations.
To describe the results of electrochemotherapy (ECT) in dogs with mast cell tumours (MCTs) either as first line therapy or as an adjuvant to surgery. The treatment combines administration of low dose ...chemotherapeutic drugs with the application of microsecond electric pulses, which cause the temporary permeabilization and increased porosity of the tumour cell membranes. The design of this study is a retrospective case series. A total of 51 dogs with MCTs were included and classified according to ECT procedure into 4 groups (ECT only, 15 cases, intra‐surgery ECT, 11, ECT Adjuvant to surgery, 14, Surgery followed by ECT, 11). The four groups (staged with location, size and grade) were evaluated to assess complete or partial remission, disease free interval, overall survival time and local toxicity. In this case series, Boxers, mixed breed and Labrador Retrievers, male dogs, between 4 and 9 years old were more represented. MCTs were predominantly grade 2 (Patnaik) and T stage 0–1, I‐1 (World Health Organization). Treated lesions were most commonly identified on the hindlimb and head where curative surgery would involve cosmetic or functional compromise. The intra‐surgery group of dogs showed the best disease free interval with Kaplan–Meyer analysis. Local toxicity induced by ECT ranged mostly from 1 to 4 in a 5‐point arbitrary scale with 0 – no toxicity to 5 – highest toxicity. In this study, ECT can be applied successfully as an exclusive therapy in smaller MCTs as an alternative to surgery. ECT can be combined with surgery either intra‐operatively or post operatively for larger lesions without significant toxicity.
The Psc lac4 gene from Pleurotus sajor-caju has been cloned and expressed in the heterologous host Pichia pastoris, under the control of the AOX1 methanol inducible promoter. The native Ple. ...sajor-caju laccase signal sequence was effective in directing the secretion of lac4 expressed in Pic. pastoris. The control of media pH and temperature was found to be important in obtaining sufficient quantities of the protein to allow purification and subsequent biochemical characterization. The recombinant Psc Lac4 was purified to electrophoretic homogeneity and was shown to be immunologically related to Pleurotus eryngii Lac1. The purified laccase was estimated to have a molecular mass of around 59 kDa, to have a carbohydrate content of approximately 7% and a calculated pI of 4.38. The enzyme oxidized the substrates 2,2-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), 2,6-dimethoxyphenol, syringaldazine and guaiacol, exhibiting optimal pHs of 3.3, 6, 6.5 and 7 respectively. With ABTS as substrate the enzyme displayed optimal activity at 35 degrees C and pH 3.5. The enzyme was strongly inhibited by sodium azide and thioglycolic acid but not by EDTA.
This paper draws together the results from a co-ordinated study, known as the World-Wide Failure Exercise, whereby 12 of the leading theories for predicting failure in composite laminates have been ...tested against experimental evidence. The comparison has been effected through 14 carefully selected test cases, which include biaxial strength envelopes for a range of unidirectional and multi-directional laminates, and stress–strain curves for a range of multi-directional laminates, loaded under uniaxial or biaxial conditions. The predictions were provided by the originators of the theories, not by third parties, and were made without access to the experimental results beforehand. The predictions and experimental data have been compared in a systematic and detailed manner, to identify the strengths and weaknesses of each theory, together with a ranking of the overall effectiveness of each theory. Careful reading of this analysis and study of the figures provided will inform the reader when selecting an appropriate failure theory for use in a given design situation. It will also provide a qualitative assessment of the likely accuracy and reliability of the prediction in a given circumstance.
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