Patterns of tumor response in canine and feline cancer patients treated with electrochemotherapy: preclinical data for the standardization of this treatment in pets and humans

Electrochemotherapy (ECT) is a novel anticancer therapy that is currently being evaluated in human and pet cancer patients. ECT associates the administration of an anti-tumor agent to the delivery of trains of appropriate waveforms. The increased uptake of chemotherapy leads to apoptotic death of the neoplasm thus resulting in prolonged local control and extended survival. In this paper we describe the histological features of a broad array of spontaneous tumors of companion animals receiving pulse-mediated chemotherapy. Multivariate statistical analysis of the percentage of necrosis and apoptosis in the tumors before and after ECT treatment, shows that only a high percentage of necrosis and apoptosis after the ECT treatment were significantly correlated with longer survivals of the patients (p < 0.0001 and p = 0.004, respectively). Further studies on this topic are warranted in companion animals with spontaneous tumors to identify new molecular targets for electrochemotherapy and to the develop new therapeutical protocols to be translated to humans

Tumor Suppressors and Cell-Cycle Proteins in Lung Cancer

The cell cycle is the cascade of events that allows a growing cell to duplicate all its components and split into two daughter cells. Cell cycle progression is mediated by the activation of a highly conserved family of protein kinases, the cyclin-dependent kinases (CDKs). CDKs are also regulated by related proteins called cdk inhibitors grouped into two families: the INK4 inhibitors (p16, p15, p19, and p18) and the Cip/Kip inhibitors (p21, p27, and p53). Several studies report the importance of cell-cycle proteins in the pathogenesis and the prognosis of lung cancer. This paper will review the most recent data from the literature about the regulation of cell cycle. Finally, based essentially on the data generated in our laboratory, the expression, the diagnostic, and prognostic significance of cell-cycle molecules in lung cancer will be examined

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Bioprosthetic Valve Fracture After TAVR Complicated by Balloon Rupture: Bail-Out TAVR in TAVR in SAVR

Transcatheter aortic valve replacement in surgical aortic valve is a safe and effective procedure to treat patients with failed bioprosthetic surgical valves at high risk for reoperation. Performing bioprosthetic valve fracture has been shown to improve postprocedural hemodynamics of TAVR in surgical aortic valve replacement. However, specific complications related to valve fracture are becoming more common. (Level of Difficulty: Advanced.)

Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

Background: The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI) increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study.Methods: Thirty-four companion animals (27 dogs and 7 cats) were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats) whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols.Results: The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6%) the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17%) experienced short lived partial responses (1-3 months duration) while all the others died of progressive disease within two months.Conclusions: high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of the quality of life in pets with down staged cancer and in the majority of the treated animals PPI were well tolerated. Further studies are warranted to assess the efficacy of this strategy in patients with advanced cancers in companion animals as well as in humans. © 2011 Spugnini et al; licensee BioMed Central Ltd

Identification of genes down-regulated during lung cancer progression: A cDNA array study

<p>Abstract</p> <p>Background</p> <p>Lung cancer remains a major health challenge in the world. Survival for patients with stage I disease ranges between 40–70%. This suggests that a significant proportion of patients with stage I NSCLC may actually be under-staged.</p> <p>Methods</p> <p>In order to identify genes relevant for lung cancer development, we carried out cDNA array experiments employing 64 consecutive patients (58 men and 6 women) with a median age of 58 years and stage 1 or stage 2 non-small-cell lung cancer (NSCLC).</p> <p>Results</p> <p>Basic cDNA array data identified 14 genes as differentially regulated in the two groups. Quantitative RT-PCR analysis confirmed an effective different transcriptional regulation of 8 out of 14 genes analyzed. The products of these genes belong to different functional protein types, such as extra-cellular matrix proteins and proteases (<it>Decorin </it>and <it>MMP11</it>), genes involved in DNA repair (<it>XRCC1</it>), regulator of angiogenesis (<it>VEGF</it>), cell cycle regulators (<it>Cyclin D1</it>) and tumor-suppressor genes (<it>Semaphorin 3B</it>, <it>WNT-5A </it>and retinoblastoma-related <it>Rb2/p130</it>). Some previously described differences in expression patterns were confirmed by our array data. In addition, we identified and validated for the first time the reduced expression level of some genes during lung cancer progression.</p> <p>Conclusion</p> <p>Comparative hybridization by means of cDNA arrays assisted in identifying a series of novel progression-associated changes in gene expression, confirming, at the same time, a number of previously described results.</p

Prevalence and Predictors of Out-of-Target LDL Cholesterol 1 to 3 Years After Myocardial Infarction. A Subanalysis From the EYESHOT Post-MI Registry

Background: There is an incomplete understanding of the prevalence and predictors of attainment of low-density lipoprotein cholesterol (LDL-C) goal after myocardial infarction (MI). Aim: To evaluate the prevalence of achievement of LDL-C goal of 70 mg/dL, to identify the baseline features associated with suboptimal lipid control, and to assess the use of LDL-C-lowering drug therapies (LLT) beyond the first year after MI. Methods: The EYESHOT Post-MI was a prospective, cross-sectional, Italian registry, which enrolled patients presenting to cardiologist 1 to 3 years after MI. In this retrospective post-hoc analysis, patients were categorized in 2 groups according to the achievement or not of the LDL-C goal of 70 mg/dL. Univariable and multivariable logistic regression analyses were performed to identify the baseline features associate with LDL-C &gt;= 70 mg/dL. Results: The study population included 903 patients (mean age 65.5 +/- 11.5 years). Among them, LDL-C was &gt;= 70 mg/dL in 474 (52.5%). Male sex (p = 0.031), hypertension (p = 0.024), prior percutaneous coronary intervention (p = 0.016) and high education level (p = 0.008) were higher in the LDL-C &lt; 70 group. At multivariable analysis, low education level was an independent predictor of LDL-C &gt;= 70 mg/dL (OR:1.582; 95%CI, 1.156-2.165; p = 0.004). Conversely, hypertension increased the probability to achieve the LDL-C goal (OR:0.650; 95%CI, 0.443-0.954; p = 0.028). Among off-target patients, LLT was not modified in the majority of cases (67.3%), intensified in 85 (18.6%), and actually reduced in 63 patients (13.8%). Conclusions: In patients presenting to cardiologists 1 to 3 years from the last MI event, LDL-C is not under control in a large proportion of patients, particularly in those with a low education level or without hypertension. LLT is underused in this very-high-risk setting

Peripartum cardiomyopathy

Peripartum cardiomyopathy is an uncommon form of congestive heart failure associated with systolic dysfunction of left ventricle. The onset is characterised by symptoms of heart failure occurring between the last month of pregnancy and 5-6 months postpartum. The early diagnosis and the institution of medical treatment for this disease are essential because the inadequate management may affect the patient’s long-term prognosis and can lead to severe complications, including death.Currently its aetiology is not completely understood. Many aetiopathogenetic hypotheses have been formulated: inflammation, viral agents, autoimmune processes. In the last years, evidences aroused for a role of prolactin and its 16 kDa metabolite in reducing cardiomyocite metabolic activity and contraction. In this article we have reviewed the current literature with special emphasis on the role of prolactin and the related current treatment strategies. In particular, bromocriptine appears promising, even if women need to be informed that the drug stops the production of breastmilk. Further researchers, such as large multicenter trials, are needed to decide the best treatment for the women suffering of this disease

Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

Sticker's sarcoma (also known as transmissible venereal tumor) is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT), treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy). Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations

Adjuvant electrochemotherapy in veterinary patients: a model for the planning of future therapies in humans

The treatment of soft tissue tumors needs the coordinated adoption of surgery with radiation therapy and eventually, chemotherapy. The radiation therapy (delivered with a linear accelerator) can be preoperative, intraoperative, or postoperative. In selected patients adjuvant brachytherapy can be adopted. The goal of these associations is to achieve tumor control while maximally preserving the normal tissues from side effects. Unfortunately, the occurrence of local and distant complications is still elevated. Electrochemotherapy is a novel technique that combines the administration of anticancer agents to the application of permeabilizing pulses in order to increase the uptake of antitumor molecules. While its use in humans is still confined to the treatment of cutaneous neoplasms or the palliation of skin tumor metastases, in veterinary oncology this approach is rapidly becoming a primary treatment. This review summarizes the recent progresses in preclinical oncology and their possible transfer to humans