This research explores the factors contributing to the injury severity of bicyclists in bicycle–motor vehicle accidents using a multinomial logit model. The model predicts the probability of four ...injury severity outcomes:
fatal,
incapacitating,
non-incapacitating, and
possible or no injury. The analysis is based on police-reported accident data between 1997 and 2002 from North Carolina, USA. The results show several factors which more than double the probability of a bicyclist suffering a fatal injury in an accident, all other things being kept constant. Notably, inclement weather, darkness with no streetlights, a.m. peak (06:00
a.m. to 09:59
a.m.), head-on collision, speeding-involved, vehicle speeds above 48.3
km/h (30
mph), truck involved, intoxicated driver, bicyclist age 55 or over, and intoxicated bicyclist. The largest effect is caused when estimated vehicle speed prior to impact is greater than 80.5
km/h (50
mph), where the probability of fatal injury increases more than 16-fold. Speed also shows a threshold effect at 32.2
km/h (20
mph), which supports the commonly used 30
km/h speed limit in residential neighborhoods. The results also imply that bicyclist fault is more closely correlated with greater bicyclist injury severity than driver fault.
Research on bladder neoplasms in pediatric and teen patients (BNPTP) has
described 21 genes, which are variously involved in this disease and are mostly responsible
for deregulated cell ...proliferation. However, due to the limited number of
publications on this subject, it is still unclear what type of relationships there are
among these genes and which are the chances that, while having different molecular
functions, they i) act as downstream effector genes of well-known pro- or anti- proliferative stimuli and/or interplay with
biochemical pathways having oncological relevance or ii) are specific and, possibly, early biomarkers of these pathologies.
A Gene Ontology (GO)-based analysis showed that these 21 genes are involved in biological processes, which can
be split into two main classes: cell regulation-based and differentiation/development-based. In order to understand the involvement/
overlapping with main cancer-related pathways, we performed a meta-analysis dependent on the 189 oncogenic
signatures of the Molecular Signatures Database (OSMSD) curated by the Broad Institute. We generated a binary
matrix with 53 gene signatures having at least one hit; this analysis i) suggests that some genes of the original list show
inconsistencies and might need to be experimentally re- assessed or evaluated as biomarkers (in particular, ACTA2) and
ii) allows hypothesizing that important (proto)oncogenes (E2F3, ERBB2/HER2, CCND1, WNT1, and YAP1) and (putative)
tumor suppressors (BRCA1, RBBP8/CTIP, and RB1-RBL2/p130) may participate in the onset of this disease or
worsen the observed phenotype, thus expanding the list of possible molecular targets for the treatment of BNPTP.
Research on bladder neoplasms in pediatric and teen patients (BNPTP) has described 21 genes, which are variously involved in this disease and are mostly responsible for deregulated cell ...proliferation. However, due to the limited number of publications on this subject, it is still unclear what type of relationships there are among these genes and which are the chances that, while having different molecular functions, they i) act as downstream effector genes of well-known pro- or anti- proliferative stimuli and/or interplay with biochemical pathways having oncological relevance or ii) are specific and, possibly, early biomarkers of these pathologies. A Gene Ontology (GO)-based analysis showed that these 21 genes are involved in biological processes, which can be split into two main classes: cell regulation-based and differentiation/development-based. In order to understand the involvement/overlapping with main cancer-related pathways, we performed a meta-analysis dependent on the 189 oncogenic signatures of the Molecular Signatures Database (OSMSD) curated by the Broad Institute. We generated a binary matrix with 53 gene signatures having at least one hit; this analysis i) suggests that some genes of the original list show inconsistencies and might need to be experimentally re- assessed or evaluated as biomarkers (in particular, ACTA2) and ii) allows hypothesizing that important (proto)oncogenes (E2F3, ERBB2/HER2, CCND1, WNT1, and YAP1) and (putative) tumor suppressors (BRCA1, RBBP8/CTIP, and RB1-RBL2/p130) may participate in the onset of this disease or worsen the observed phenotype, thus expanding the list of possible molecular targets for the treatment of BNPTP.
The need for more appropriate animal models in cancer research has led, over the past 20 years, to consider pets with spontaneously occurring neoplasms as a valuable and still under used resource. ...The role of companion animals in the struggle to eradicate cancer can be multiple: they may act as environmental sentinels, help in gaining insights on tumor biology and finally may be enrolled in therapeutic trials which might act as a bridge to the clinic applications. This paper will focus on the most valuable spontaneous neoplasms in companion animals and will analyze the potentials of each histotype as a model for basic research and for new therapeutic strategies. It is conceivable that in the next years comparative oncology will play a paramount role in translational medicine allowing a rapid flow of data from laboratories to clinical application in humans.
The objectives of this phase I/II study were: i) to determine whether electrochemotherapy (intralesional bleomycin + electric pulses) could be effective in companion animals with different, large ...neoplasms compared to chemotherapy (conventional intralesional bleomycin); ii) to identify potential toxicities; iii) to preliminarily assess the electric field requirements. Twenty-two patients received intralesional bleomycin + administration of permeabilizing electric pulses. Specifically, after the injection of the drug, sequences of 8 biphasic electric pulses lasting 50 + 50 micros each, with 1 ms interpulse intervals, were delivered in bursts of 1300 V/cm for cutaneous and soft tissue lesions, and of 800 V/cm for oral mucosal and exposed soft tissue neoplasms, using caliper electrodes. The treatment was well tolerated and side effects were infrequent. Nevertheless, two previously unreported toxicities (drug-induced vasculitis and pulmonary thromboembolism) have been identified. A high response rate (complete remission + partial remission: > 80%), often long lasting (> 40%) was obtained. Furthermore, results of this trial were compared to a subset of veterinary cancer patients treated with bleomycin single agent, observing a remarkable superiority of the combined treatment (p < 0.01). Altogether, results suggest that electrochemotherapy is a potentially advantageous rescue protocol for bulky, even relapsing neoplasms of companion animals. Further investigations in this field might allow developing improved protocols for the treatment of down-staged relapsing cancer in pets as well as in humans.
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.
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.
Aside from the well-established roles of c-Myc in the regulation of cell cycle, differentiation, and apoptosis, a recent picture is beginning to emerge linking c-Myc to the regulation of metabolic ...pathways. Here, we define a further function for c-Myc in determining cellular redox balance, identifying glutathione (GSH) as the leading molecule mediating this process. The link between c-Myc and GSH is γ-glutamyl-cysteine synthetase (γ-GCS), the rate-limiting enzyme catalyzing GSH biosynthesis. Indeed, c-Myc transcriptionally regulates γ-GCS by binding and activating the promoters of both γ-GCS heavy and light subunits. Exposure to H
2O
2 enhances c-Myc recruitment to γ-GCS regulatory regions through ERK-dependent phosphorylation. Phosphorylation at Ser-62 is required for c-Myc recruitment to γ-GCS promoters and determines the cellular response to oxidative stress induced by different stimuli. Thus, the c-Myc phosphorylation-dependent activation of the GSH-directed survival pathway can contribute to oxidative stress resistance in tumor cells, which generally exhibit deregulated c-Myc expression.
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