Book review of: "Clinical aspects of electroporation" by Stephen T Kee, Julie Gehl, Edward W Lee

This article is a review of the book: Clinical aspects of electroporation, by Stephen T. Kee, Julie Gehl, Edward W Lee, which is published by Springer Press. Basic information that should be helpful in deciding whether to read the book and whether to use it as a reference book is presented. This includes an introduction, a description of all the sections of the book, and a comparison with recently published books on the topic

Primary Perianal Malignant Melanoma in a Dog - Combination Therapy

Background: Melanocytic neoplasm can arise from melanocytes in any location of the body. Malignant melanoma (MM) has a poor prognosis in dogs and presence of lymphvascular invasion, distant metastasis, or mitotic activity present prognostic value. Primary melanoma affecting the gastrointestinal tract has been rarely reported in veterinary literature, thus the prognosis affecting gastrointestinal tract is unknown. Electrochemotherapy (ECT) is an effective local treatment which combines chemotherapeutic drugs mainly bleomycin or cisplatin followed by the delivery of permeabilizing electrical pulses However, other hydrophilic drugs seem to present an increase cytotoxic effect such as carboplatin.Case: A 9-year-old mixed-breed neutered dog was referred to a private clinic with a mass in the perianal region diagnosed as perianal melanoma. No metastasis was observed on abdominal ultrasound nor chest x-ray (3 views). Clinical signs noted were tenesmus, hemorrhagic discharge, weight loss and hyporexia. Considering the tumor volume (16.0 x 10.0 cm), a neoadjuvant ECT session was proposed. The authors opted for carboplatin (300 mg/m², intravenously), administered over 20 min and cisplatin intratumorally (1 mg/cm³, equivalent to 1 mL/1cm³; total volume 20 mL) administered in the upper parts of the mass that could be reached while avoiding drug leakage. After administration, sequences of eight biphasic pulses, (100 microseconds), with a voltage ranging from 650-1,000V/cm (pulse generator Onkodisruptor®) using a hexagonal/single pair and plate electrode were delivered. At day 30th, a partial response was observed accordingly to RECIST system, with tumor size of 5.0 x 5.0 cm (65.4 cm³). A second ECT session was performed with the same previous protocol, but with a decreased dosage of carboplatin (240 mg/m² consistent with 20% reduction) due to adverse effects in the first session, resulting in stable disease at day 60th (30 days after second ECT). Then, we proposed a surgical excision of the mass including partial resection of ventral rectum with intraoperative ECT. Afterwards, it was observed fecal incontinence that did not resolved after time but did not significant cause a morbidity in the patient. Patient achieved a disease-free interval (DFI) of 700 days and survival time of 730 days. Unfortunately, patient died due to distant metastasis.Discussion: Surgery is still the cornerstone treatment for MM in dogs, regardless anatomic site. However, in perianal region, wide or radical local surgical excision is a challenge due to anatomic region which precluded most of the time to achieve complete margins. In this report, the origin of the tumors was not defined since no normal tissue was found surrounding tumors cells probably due to tumor invasion and destruction of surrounding tissue. Thus, based on the previous literature, this tumor could have been arisen from rectum wall or anal sac. The longer DFI and survival time from this patient is superior from the most veterinary cases in literature which combined different types of treatment such as surgery, chemotherapy, immunotherapy, palliative care or ECT. Neoadjuvant ECT leaded to a reliable approach for partial remission in order to perform a better surgical approach in this case report. To conclude, ECT may be an option for partial remission and local control in regions which anatomic limitation is a challenge for wide excision.Keywords: bleomycin, carboplatin, cisplatin, electroporation, melanocytic tumor

Electrochemotherapy with cisplatin enhances local control after surgical ablation of fibrosarcoma in cats: an approach to improve the therapeutic index of highly toxic chemotherapy drugs

<p>Abstract</p> <p>Background</p> <p>Cancer is one of the most difficult current health challenges, being responsible for millions of deaths yearly. Systemic chemotherapy is the most common therapeutic approach, and the prevailing orientation calls for the administration of the maximum tolerated dose; however, considerable limitations exist including toxicities to healthy tissues and low achievable drug concentrations at tumor sites. Electrochemotherapy (ECT) is a tumor treatment that combines the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses. In this article we evaluate the capability of ECT to allow the use of cisplatin despite its high toxicity in a spontaneous feline model of soft tissue sarcoma.</p> <p>Methods</p> <p>A cohort of sixty-four cats with incompletely excised sarcomas were treated with cisplatin-based adjuvant ECT and monitored for side effects. Their response was compared to that of fourteen cats treated with surgery alone.</p> <p>Results</p> <p>The toxicities were minimal and mostly treated symptomatically. ECT resulted in increased local control (median not reached at the time of writing) with a mean time to recurrence of 666 days versus 180 of controls.</p> <p>Conclusions</p> <p>We conclude that ECT is a safe and efficacious therapy for solid tumors; its use may be considered as part of strategies for the reintroduction of drugs with a narrow therapeutic index in the clinical protocols.</p

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

Proton pump inhibitors for the treatment of cancer in companion animals

The treatment of cancer presents a clinical challenge both in human and veterinary medicine. Chemotherapy protocols require the use of toxic drugs that are not always specific, do not selectively target cancerous cells thus resulting in many side effects. A recent therapeutic approach takes advantage of the altered acidity of the tumour microenvironment by using proton pump inhibitors (PPIs) to block the hydrogen transport out of the cell. The alteration of the extracellular pH kills tumour cells, reverses drug resistance, and reduces cancer metastasis. Human clinical trials have prompted to consider this as a viable and safe option for the treatment of cancer in companion animals. Preliminary animal studies suggest that the same positive outcome could be achievable. The purpose of this review is to support investigations into the use of PPIs for cancer treatment cancer in companion animals by considering the evidence available in both human and veterinary medicine

Ultrasound guided electrochemotherapy for the treatment of a clear cell thymoma in a cat

A twelve-year-old male castrated domestic shorthair cat was presented for rapidly progressing respiratory distress. The cat was depressed, tachypneic and moderately responsive. Ultrasonography showed a mediastinal mass associated with a significant pleural effusion that needed tapping every five to seven days. Ultrasound guided biopsy yielded a diagnosis of clear cell thymoma upon histopathology. After complete staging procedures, the owner elected to treat the cat with electrochemotherapy (ECT) using systemic bleomycin. Two sessions of ultrasound guided ECT were performed at two week intervals with trains of biphasic electric pulses applied using needle electrodes until complete coverage of the area was achieved. The treatment was well tolerated and resulted in partial remission (PR). Additional sessions were performed on a monthly basis. The cat is still in PR after fourteen months. ECT resulted in improved local control and should be considered among the available adjuvant treatments in pets carrying visceral tumors

Electrochemotherapy: An Alternative Strategy for Improving Therapy in Drug-Resistant SOLID Tumors

Electrochemotherapy (ECT) is one of the innovative strategies to overcome the multi drug resistance (MDR) that often occurs in cancer. Resistance to anticancer drugs results from a variety of factors, such as genetic or epigenetic changes, an up-regulated outflow of drugs, and various cellular and molecular mechanisms. This technology combines the administration of chemotherapy with the application of electrical pulses, with waveforms capable of increasing drug uptake in a non-toxic and well tolerated mechanical system. ECT is used as a first-line adjuvant therapy in veterinary oncology, where it improves the efficacy of many chemotherapeutic agents by increasing their uptake into cancer cells. The chemotherapeutic agents that have been enhanced by this technique are bleomycin, cisplatin, mitomycin C, and 5-fluorouracil. After their use, a better localized control of the neoplasm has been observed. In humans, the use of ECT was initially limited to local palliative therapy for cutaneous metastases of melanoma, but phase I/II studies are currently ongoing for several histotypes of cancer, with promising results. In this review, we described the preclinical and clinical use of ECT on drug-resistant solid tumors, such as head and neck squamous cell carcinoma, breast cancer, gynecological cancer and, finally, colorectal cancer