Anticancer activity of "Trigno M", extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models

Abstract In 2018 there were over 1.8 million new cases worldwide of colorectal cancer and relapses after clinical treatments. Many studies ascribe the risk of the appearance of this cancer to the Western life style : a sedentary life, obesity, and low -fiber, high -fat diets can promote the onset of disease. Several studies have shown supplement phytochemicals to have an inhibiting effect on the growth of various cancers through the activation of apoptosis. Our goal was to prove the effectiveness of a natural compound in the combined therapy of colorectal cancer. Trigno M supplement was an optimal candidate as anticancer product for its high concentrations of phenolic acids, flavonoids and anthocyanins. Our work showed the antitumor activity of Trigno M, extract of Prunus spinosa drupes combined with the nutraceutical activator complex (NAC), in 2D, 3D and in vivo colorectal cancer models. The cellular model we used both in vitro and in vivo was the HCT116 cell line, particularly suitable for engraftment after inoculation in mice. Trigno M inhibited the growth and colony formation of HCT116 cells (35%) as compared to the chemotherapy treatment with 5-fluorouracil (80%) used in clinical therapy. The reduction of the morphological dimensions in the spheroid cells after Trigno M, was compared with 5-fluorouracil demonstrating the efficacy of the Trigno M compound also in 3D models. Flow cytometric analysis on 3D cells showed a significant increase in the apoptotic cell fraction after Trigno M treatment (44.8%) and a low level of necrotic fraction (6.7%) as compared with control cells. Trigno M and 5-fluorouracil induced the apoptosis in a comparable percentage. Monotherapy with Trigno M in severely immunodeficient mice, carrying colon rectal cancer xenografts, significantly reduced tumor growth. The histopatological analysis of the ectopic tumors showed a lower level of necrosis after Trigno M treatment compared with the control. We conclude that Trigno M is well tolerated by mice, delays colorectal cancer growth in these animals and should be weighed up for integration of the current multi-drug protocols in the treatment of colon carcinoma

RIP1-HAT1-SirT complex identification and targeting in treatment and prevention of cancer

Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8-mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene-induced mammary gland hyperproliferation in vivoConclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention

Electroporation in laboratory and clinical investigations

Electroporation is a widespread technique adopted to increase the uptake of molecules by biological targets. This approach is gaining momentum due to its low cost and feasibility both in basic and in applied science. Notwithstanding the raise in interest in this method at scientific and clinical level, there are very few books completely dedicated to this argument. The principal purpose of this book is a comprehensive and up to date overview on electroporation in mathematic modeling, bioengineering, molecular biology, plant biology, pathology, veterinary and human oncology. © 2012 by Nova Science Publishers, Inc. All rights reserved

Electrochemotherapy in Veterinary Oncology: State-of-the-Art and Perspectives

Tumor microenvironment represents a key obstacle for the effectiveness of anticancer drugs. Electrochemotherapy involves the systemic or local delivery of lipophobic drugs such as bleomycin and cisplatin, with the application of permeabilizing electric pulses having appropriate amplitude and waveforms. This greatly enhances the uptake of these drugs by an estimated factor of 700-fold for bleomycin and 4 to 8 times for cisplatin. Because of its efficacy and limited morbidity, this therapeutic option is becoming more and more available in veterinary oncology either as an adjuvant to surgery or as first line of treatment with palliative or curative purposes

Surgery and electrochemotherapy for the treatment of cutaneous squamous cell carcinoma in a yellow-bellied slider (Trachemys scripta scripta)

Case Description—A 5-year-old female yellow-bellied slider (Trachemys scripta scripta) was referred for evaluation of a 2-month nonhealing ulcerated mass on the dorsal aspect of the neck. Clinical Findings—The turtle was quiet, alert, and responsive, with a 2 X 1.5-cm ulcerated lesion on the neck. Signs of discomfort were observed during manipulation of the neck; no other abnormalities were detected during physical evaluation. Treatment and Outcome—Following total body radiography and hematologic and serum biochemical analysis, the turtle was anesthetized and the mass was surgically removed. The excised tissue was submitted for histologic evaluation. A histopathologic diagnosis of squamous cell carcinoma (SCC) was made. Further surgical revision was not an option because of the extensive nature of the lesion; therefore, the tumor bed was treated with electrochemotherapy (ECT). Two sessions of ECT were performed with a 2-week interval between treatments. Electrochemotherapy involved intratumoral administration of bleomycin followed by trains of biphasic electric pulses. The treatment was well tolerated, and the turtle was disease free after 12 months. Clinical Relevance—ECT resulted in good local control of SCC and should be considered as a possible postsurgical adjuvant treatment in reptiles with cutaneous tumors. (J Am Vet Med Assoc 2015;246:455–457

Successful Treatment of a Keratoacanthoma with Electrochemotherapy: A Case Report

Few studies have evaluated the efficacy of intralesional bleomycin injection combined with electroporation for the treatment of cutaneous tumors. However, the phenomenon that electroporation can enhance the cytotoxicity of bleomycin in vivo by 300-700 fold has been intensely investigated.Introduction: Few studies have evaluated the efficacy of intralesional bleomycin injection combined with electroporation for the treatment of cutaneous tumors. However, the phenomenon that electroporation can enhance the cytotoxicity of bleomycin in vivo by 300–700 fold has been intensely investigated. Case Presentation: Keratoacanthoma in an 86-year-old patient was treated with intralesional bleomycin combined with electroporation. Treatment consisted of local application of shorty and intense electric pulses followed by local injection of bleomycin. Electroporation was always well tolerated by the patient, with no significant complaints, and the tumor had completely regressed by day 71 of the follow-up. Conclusion: The results suggest that intralesional bleomycin injection combined with electroporation could represent a valid alternative therapeutic approach for the treatment of keratoacanthomas

COX-2 overexpression in canine tumors: potential therapeutic targets in oncology

Cyclooxygenases catalyze the initial, ratelimiting 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