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

Cancer astrocytes have a more conserved molecular status in long recurrence free survival (RFS) IDH1 wild-type glioblastoma patients: New emerging cancer players

Glioblastoma is a devastating disease that despite all the information gathered so far, its optimal management remains elusive due to the absence of validated targets from clinical studies. A better clarification of the molecular mechanisms is needed. In this study, having access to IDH1 wild-type glioblastoma of patients with exceptionally long recurrence free survival (RFS), we decided to compare their mutational and gene expression profile to groups of IDH1 wild-type glioblastoma of patients with shorter RFS, by using NGS technology. The exome analysis revealed that Long-RFS tumors have a lower mutational rate compared to the other groups. A total of 158 genes were found differentially expressed among the groups, 112 of which distinguished the two RFS extreme groups. Overall, the exome data suggests that shorter RFS tumors could be, chronologically, in a more advanced state in the muli-step tumor process of sequential accumulation of mutations. New players in this kind of cancer emerge from the analysis, confirmed at the RNA/DNA level, identifying, therefore, possible oncodrivers or tumor suppressor genes

Metabolic-imaging of human glioblastoma live tumors: A new precision-medicine approach to predict tumor treatment response early

Glioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients

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

Histological and Immunohistochemical Characterization of a Case of Endometriosis in a Guinea Pig (Cavia tschudii)

Endometriosis is a chronic gynecological disease characterized by the ectopic proliferation of endometrial tissue outside of the uterine cavity. The pathogenesis of this disease is still obscure, and Sampson’s theory of retrograde menstruation is still the most widely accepted explanation. Endometriosis in animals has been so far described not only in baboons and a rhesus macaque but also in dogs and horses that are nonmenstruating animals. In this article, we report the histological and immunohistochemical characterization of the first case of ovarian cystic endometriosis and adenomyosis in a guinea pig. The case presented supports the hypothesis that endometriosis is a disease not at all related to the phenomenon of retrograde menstruation but is a consequence of some alterations in the morphogenesis of the female genital system and therefore it could be found in any mammal. We suggest considering endometriosis among the other pathological phenotypes in animals displaying ovarian and uterine alterations and having a history of difficulties in conceiving

Symbolic incentives can affect the frequency of blood and plasma donations: Evidence from 12 years of donors’ behavior and donation awards

We use panel data (from 2008 to 2019) covering the entire population of blood and plasma donors affiliated to an association of donors (AVIS) in an Italian region (Tuscany) to examine how donors respond to a nonlinear scheme of symbolic incentives (medals) related to donation quotas and length of membership. The structure of the award scheme allows us to study the impact of two distinct characteristics of the symbolic awards: the private vs. public assignment, and the donation-only vs. donation-and-membership criterion (although this latter characteristic can only be distinguished for private assignments). When we control for unobservable individual characteristics potentially affecting the evolution of performance along a donor’s career we find that: (i) public assignment of medals has an impact which is not appreciably different from the one with private assignment, (ii) the donation-and-membership criterion induces an ex-post increase in the frequency of donations, while the donation-only criterion does not. This evidence suggests that symbolic awards are useful if given to less performing donors, that they affect behavior after their obtainment rather than before, and that they operate when their obtainment does not exclusively depend on performance, but also on membership

Combination of bleomycin and cisplatin as adjuvant electrochemotherapy protocol for the treatment of incompletely excised feline injection site sarcomas: A retrospective study

Background: Feline injection-site sarcomas (FISS) are mesenchymal tumors that can occur in cats after injections of different medical agents, and are easily prone to recurrence. Aim: The aims of this study were to report treatment outcomes for cats with feline injection site sarcomas (FISS) treated with both bleomycin and cisplatin, per adjuvant electrochemotherapy (ECT) protocol. Methods: Medical records of cats with a diagnosis of FISS that were treated with ECT using both bleomycin and cisplatin were retrospectively evaluated. Twenty-seven cats were available for statistical evaluation of their response. The cats received intravenous 20 mg/m2 bleomycin, and the tumor bed and margins were infiltrated with cisplatin at the dose of 0.5 mg/cm2. Then, trains of permeabilizing biphasic electric pulses lasting 50 + 50 µsec each, were delivered in bursts of 1,300 V/cm using caliper electrodes under sedation. A second session was performed 2 weeks later. Results: Side effects were limited to local inflammation in three cats. Three cats developed local tumor recurrence at days 180, 180 and 545, after surgery, two cats developed recurrence and metastases at 100 and 505 days after surgery and two cats experienced distant metastases. A median time to recurrence could not be calculated as over 80% of the study population remained disease-free or were censored due to death from other causes. Mean survival time was 985 days and median cumulative survival for all cases, was 1000 days. Conclusion: When compared to historical controls, the results of this study demonstrate superior rates of tumor-free survival and disease-free interval. This adjuvant therapy could be a useful addition to the current options for FISS in consideration of its efficacy, limited toxicity, and ease of administration

Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation

Glioblastoma (GBM) is the most common form of malignant brain cancer and is considered the deadliest human cancer. Because of poor outcomes in this disease, there is an urgent need for progress in understanding the molecular mechanisms of GBM therapeutic resistance, as well as novel and innovative therapies for cancer prevention and treatment. The pentose phosphate pathway (PPP) is a metabolic pathway complementary to glycolysis, and several PPP enzymes have already been demonstrated as potential targets in cancer therapy. In this work, we aimed to evaluate the role of sedoheptulose kinase (SHPK), a key regulator of carbon flux that catalyzes the phosphorylation of sedoheptulose in the nonoxidative arm of the PPP. SHPK expression was investigated in patients with GBM using microarray data. SHPK was also overexpressed in GBM cells, and functional studies were conducted. SHPK expression in GBM shows a significant correlation with histology, prognosis, and survival. In particular, its increased expression is associated with a worse prognosis. Furthermore, its overexpression in GBM cells confirms an increase in cell proliferation. This work highlights for the first time the importance of SHPK in GBM for tumor progression and proposes this enzyme and the nonoxidative PPP as possible therapeutic targets

Evaluation of electrochemotherapy in the management of anal sac apocrine gland adenocarcinomas in dogs: A retrospective study

Background: Electrochemotherapy (ECT) combines the administration of anticancer drugs with the delivery of electric pulses, thus increasing the drug uptake through the cell membranes, resulting in increased efficacy. Aim: The aim of our study was to describe the tolerability and efficacy of ECT alone or in association with other treatment modalities for the management of Apocrine Gland Anal Sac Adenocarcinoma (AGASAC). Methods: Medical records of dogs with a diagnosis of AGASAC that were treated with ECT alone or in combination with surgery/chemotherapy were retrospectively evaluated. Each dog received 20 mg/m2 of bleomycin intravenously. Based on the clinician decision, the primary tumor or tumor bed was also infiltrated with cisplatin at the dose of 0.5 mg/cm2. Trains of permeabilizing biphasic electric pulses were then applied under general anaesthesia. Results: Ten dogs were enrolled in the study. Of those ten dogs, only one received ECT for treatment of microscopic local disease, while in 6 cases ECT was the only treatment modality. In 3 dogs, ECT was followed by systemic medical treatment. Six dogs (60%) had a partial response (PR), 3 dogs (30%) had stable disease (SD), and one dog treated for microscopic disease did not show any sign of local relapse 305 days after treatment, being still alive and in complete remission (CR) at the time of writing. The median time to progression was 303 days and the median survival time was 365 days. The treatment was well tolerated and local side effects were minimal. No systemic effects were documented. Conclusion: This preliminary study suggests that ECT may be beneficial for dogs with AGASAC and could be a useful addition to the current therapeutic options in consideration of its low cost, limited toxicity, and ease of administration

Prosocial behavior in emergencies: Evidence from blood donors recruitment and retention during the COVID-19 pandemic

The impact of COVID-19 represents a specific challenge for voluntary transfusional systems sustained by the intrinsic motivations of blood donors. In general, health emergencies can stimulate altruistic behaviors. However, in this context, the same prosocial motivations, besides the personal health risks, could foster the adherence to social distancing rules to preserve collective health and, therefore, discourage blood donation activities. In this work, we investigate the consequences of the pandemic shock on the dynamics of new donors exploiting the individual-level longitudinal information contained in administrative data on the Italian region of Tuscany. We compare the change in new donors' recruitment and retention during 2020 with respect to the 2017–2019 period (we observe 9511 individuals), considering donors’ and their municipalities of residence characteristics. Our results show an increment of new donors, with higher proportional growth for older donors. Moreover, we demonstrate that the quality of new donors, as proxied by the frequency of subsequent donations, increased with respect to previous years. Finally, we show that changes in extrinsic motivations, such as the possibility of obtaining a free antibody test or overcoming movement restrictions, cannot explain the documented increase in the number of new donors and in their performance. Therefore, our analyses indicate that the Tuscan voluntary blood donation system was effective in dealing with the challenges posed by the COVID-19 pandemic