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Browsing by Subject "cancer"

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  • Loukola, Johanna (2021)
    Cancer is the second leading cause of death worldwide. Cancer is believed to emit volatile organic compounds (VOCs) which dogs may be able to smell. This literature review brings out previous studies about cancer detection dogs, observations made based on them and their future possibilities. There is also some information about training of the dogs, proper test settings and validating a diagnostic test. Detectable odour emissions from a patient with neoplasia, or “smell of cancer”, is an interesting topic, but it has a minor role in this work. Training of the dogs should be done with samples which disease status is confirmed so that the dogs are not rewarded for indicating wrong samples. The trainer must be able to read the dog’s signals and take care of its basic needs in order not to continue training after the dog’s concentration has deteriorated. Training should happen gradually and through positive reinforcement. There should be enough samples and they must not be the same in the testing phase as in training. In validating a diagnostic test, the main goal, materials and methods of the study must be defined and the test should be compared to a golden standard. The smell of cancer is yet unknown although there are studies of the topic. Particular VOCs, which presumably constitute the cancer smell, exist in the body’s secretions. Further studies are needed in order to understand what happens at a molecular level in cancer. There are many studies about cancer detection dogs where they try to discriminate a cancer sample among controls. In these studies, the number of dogs has varied between one to six, there are diverse breeds and dogs have different backgrounds. Good results have been achieved with only two to three weeks of training. Studies have been made of nine different cancer types and the most studied ones have been lung and prostate cancer. Urine and breath were the most common samples used. The sensitivity of cancer odour detecting dogs has varied between 18 to 100%. Previous studies have had different limitations, one of which can be considered having only one cancer sample with controls. This leads to that specificity cannot be held valid. There have been also some limitations in using dogs like short usage time because of their limited life, small number of dogs and wrong rewarding system. There should not be any systematic differences between control and cancer samples including the patient’s age and the handling procedures of samples in the study. Way of life and medications may also have an effect on the dog’s choice, but they were not taken into account in all of the studies. A small number of samples was a problem in some cases. Cancer detection dogs could possibly be used in recognizing the cancer smell, mass screenings, and surveillance after treatments, in addition to laboratory diagnostics and in the developing electronic diagnostic methods such as an artificial nose.
  • Merikallio, Sini (2021)
    Canine uveal melanoma (UM) usually manifests as a slowly developing, darker pigmented and well distinguishable mass in the iris. Less than a third of them are considered malignant, which is much less than with other melanocytic cancers. In contrast, in humans, 90% of UM occurs in the choroid and half of the patients eventually develop aggressive and often lethal metastases. Understanding the disease process and genetic background in dogs might also help us further the knowledge and improve the treatment options of humans. There is a hereditary component to the oncogenesis of the UM: the disease is more common in a Caucasian race and is also found in certain families. It is also more prevalent in certain dog breeds; Labrador Retrievers seem to be overrepresented. Several susceptibility genes have been identified in humans. One with the strongest association with UM is a tumor suppressor gene BAP1, which is dysfunctional or missing in nearly half of the human uveal melanomas. This gene is a so-called secondary driver of the UM and mutations in it spark the metastasizing process. There is a germline mutation of BAP1 in fourth of Finnish UM families and these mutations are also connected to various other cancers. Moreover, BAP1 shows over 98% protein product homology and almost 80% mRNA homology between dogs and humans, making it an appealing study target also for canines. Should a single variant account for high UM risk, a DNA test could be developed to be used in breeding and veterinary diagnostics. In this work, I mapped the BAP1 germline mutations of seven Labrador Retrievers with diagnosed uveal melanomas or melanocytomas. It was found that four dogs shared the same set of five heterozygous single nucleotide variants (SNV). One of the SNVs within exon 17 was synonymous, g.37,363,076G>A, p.(Ser721Ser), while the other four SNVs were intronic, residing close to exons 4, 10, 11 and 14. In the future, variant comparisons with healthy Labradors are needed to study the role of the identified variants for the development of UM, as the SNVs now found could also just be a part of a common variation in the Labrador Retriever gene pool. To grasp a bigger picture of the UM tumor development, the tumors themselves should also be analyzed for somatic mutations. Moreover, when we know that the disease is likely affected by over a hundred genes, studying just one gene is unnecessarily self-restricting. Modern full genome sequencing techniques should be used for catching all the predisposing genes simultaneously.