Electrochemotherapy associates the local delivery of anticancer drugs with the administration of permeabilizing electric pulses that support the antiblastic action. The basic instrumentation for this ...therapy is constituted by a pulse generator and various specific electrodes. While many efforts have been profuse by researchers in this field to obtain the standardization of the pulse generating equipment over the past 15 years, the delivery apparatus still needs refinements in order to reach most of the body districts, to control the homogeneity and stability of the electric fields and to further reduce morbidity. With the aim to develop innovative electrodes able to satisfy, at least partially, these requirements, extensive studies on pet patients with spontaneous neoplasms have been conducted, leading to the manufacturing of several different prototypes. In this paper we discuss the rationale of 11 different electrodes, briefly summarize the results obtained and their experimental validation, also presenting five paradigmatic clinical cases. In particular, it is shown that the caliper electrodes are more suited for the treatment of cutaneous and subcutaneous lesions, while the needle arrays are more efficacious in intraoperative settings. Furthermore, relevant peculiarities of unipolar electrodes are examined with a particular focus on the irregular current paths that they produce and on the potentialities of this feature. Remarkably, the decrease of the steric encumbrance turned out to be a stronger factor in electrode design than the containment of the total number of electric fields covered in serial ECT sessions. In the conclusions, perspectives and new challenges of electrode design for electrochemotherapy are illustrated.
Cyclooxygenases catalyze the initial, rate-limiting steps of prostaglandin synthesis from arachidonic acid. Two isoforms of this enzyme exist in mammalian and avian species: COX-1 and COX-2. COX-1 is ...constitutively expressed and is the major isoform of gastrointestinal tissue. COX-2 is induced in response to inflammatory stimuli. COX-2 has been implicated in carcinogenesis of several neoplasms. Furthermore, COX-2 over-expression has been noted in many solid tumours and has been correlated with a worse prognosis in colorectal cancer, non-small-cell lung cancer, mesothelioma and gastric cancer. In this review, the most recent findings on the mechanisms by which COX-2 promote tumorigenesis are discussed, with particular emphasis on the studies involving spontaneous canine neoplasms.
Accumulating evidences show a higher incidence of hepatic neoplasm in HIV/hepatitis C virus (HCV)-coinfected individuals compared with HCV-monoinfected patients. Treatment with HIV-1 protease ...inhibitors inhibited cancer-promoted angiogenesis in HIV-infected patients affected by Kaposi sarcoma. We aimed to evaluate the antineoplastic potential activities of the protease inhibitor indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models.
We analyzed effects of indinavir on cell growth and invasiveness in Huh7 and SK-HEP-1 hepatocarcinoma cell lines and on in vivo tumor growth of the same cells in nude mice. Morphologic and molecular analyses on explanted tumors were carried out to evaluate vascularization and apoptosis.
We observed a reduced ability to invade an in vitro extracellular matrix for both cell lines treated with indinavir compared with controls (P = 0,001). Moreover, indinavir treatment was able to inhibit matrix metalloproteinase-2 proteolytic activation, whereas there was no effect on cell proliferation. The drug was also able to delay in vivo tumor growth. The inhibition of tumor growth was statistically significant from days 6 to 21 (P = 0.004 and P = 0.003, respectively). Moreover, the drug showed antiangiogenic and proapoptotic actions, as revealed by vessel count and apoptotic index by terminal deoxynucleotide transferase-mediated nick end labeling in explanted tumors. Finally, treatment with indinavir did not block the production of vascular endothelial growth factor in the tumors.
Indinavir could be helpful to prevent the development of hepatocarcinomas in HIV/HCV-coinfected individuals. In view of the current trend to substitute protease inhibitors with other antiretroviral agents, this information may have clinical implications.
A 13-year-old male neutered cat was presented for the sudden growth of two nodular lesions close to the upper eyelid of both eyes. Fine-needle aspiration cytology was suggestive of mesenchymal ...neoplasia. The cat had conservative surgical excision in order to preserve the eyelids' functionality; however, the histopathological report came with a diagnosis of incompletely excised bilateral pleomorphic rhabdomyosarcoma. Due to the local aggressiveness of this neoplasm, the cat was treated with two sessions of cisplatin-based electrochemotherapy, delivered 14 days apart. Systemic or local toxicities were not detected during the whole course of therapy. The cat is still in complete remission after 12 months. Electrochemotherapy is a safe and efficacious adjuvant therapy for aggressive sarcomas and warrants further investigations in order to standardise its protocols.
Malignant mesothelioma (MM) is a rare, highly aggressive tumor that arises from the surface serosal cells (pleural, peritoneal and pericardial cavities). Epidemiological and clinical data show that ...there is an association between asbestos exposure and MM development, even if the exact mechanism whereby asbestos induces MM is unknown. The continuing identification and elucidation of the molecular defects involved in mesothelioma pathogenesis and progression should lead to better disease control and greater therapeutic options in the near future. Goal of this article is to summarize the most recent advances in molecular pathogenesis of mesothelioma with particular emphasis on genes that could be considered as biomarkers or therapeutic targets and discuss possible clinical implications of these findings.
The phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of the catalytic subunit p110 and the regulatory subunit p85. The PI3K/Akt pathway is strongly deregulated in breast cancer (BC) ...representing one of the mechanisms of resistance to therapies. Therefore, the identification of inhibitors of PI3K components represents one of the main goals to produce therapeutic agents. Here, we evaluated the efficacy of a phosphopeptide 1257 (P-1257) that targeting p85 strongly inhibits PI3K activity. We tested the effects of P-1257 administration in vitro and in vivo using BC cells expressing different levels of ErbB-2 and resistant or responsive to Trastuzumab. We demonstrated that inhibition of p85 activity by P-1257 induces cell death and sensitizes JIMT-1 and KPL-4 ErbB-2-overexpressing BC cells to Trastuzumab treatment. It is noteworthy that P-1257 delivery in vivo by electroporation or liposomes significantly inhibits the proliferation of tumor cells engrafted at subcutaneous and visceral sites. Overall, our data indicate that the p85 subunit is a valid target for therapeutic approaches and suggest that the structure of the peptide used in our study could be utilized for the development of novel drugs to apply in combination with therapies that fail to cure BCs with high PI3K activity.
Oncology has made great advancements in the past 50 years, moving from preliminary to complex studies and developing in the process numerous models. An important function in this development has been ...played by animal investigations that have displayed many aspects of cancer and led to the discovery of new therapies. Nevertheless, the debate about preclinical "tools" suited to predict efficacy as well as side effects of anticancer compounds and treatments is open. In this review we focus on the role of pet models in cancer research, whose continuously increasing importance is due to the disclosure of striking histopathological, anatomical, genetical, and biomolecular similarities among feline, canine, and human tumors. Remarkably, the improvement of clinical condition of companion animals, obtained by their enrolment in cancer trials, is generally perceived as an added value for the whole society. In the first paragraphs we examine crucial ethical, clinical, and financial issues that make up the framework of this area of translational research. Then we illustrate the new figures of researchers, namely experts in laboratory-clinic interface, who are needed in this field, and describe the relevant potentialities of pet cancer registries and genome projects. In the conclusions are summarized the principal arguments that support the adoption of pet models in tumor studies.
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