Browsing by Author "Dervisis, Nikolaos G."
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- Abdominal ultrasonographic findings at diagnosis of osteosarcoma in dogs and association with treatment outcomeSacornrattana, O.; Dervisis, Nikolaos G.; McNiel, E. A. (Wiley-Blackwell, 2013-09-01)The purpose of this study was to describe abdominal ultrasonographic findings present at diagnosis of osteosarcoma (OSA) in dogs and to investigate for associations with treatment outcome. Medical records from 118 dogs diagnosed with OSA that had abdominal ultrasonography performed as part of their initial evaluation were reviewed. Fifty-seven percent had ultrasonographic abnormalities identified. The organ with the highest frequency of ultrasonographic changes was the spleen. While most sonographic changes were considered to be either benign or of unknown clinical consequences, metastases were identified in three dogs (2.5%), two of which (1.7%) did not have other evidence of metastasis. Dogs with any ultrasonographic abnormality were less likely to receive definitive therapy (P = 0.005) and exhibited shorter survival, although the latter observation was not statistically significant (P = 0.071). However, the identification of lesions in either the liver (P = 0.021) or the kidney (P = 0.003) was statistically associated with shorter survival.
- Bacteria-Enabled Autonomous Drug Delivery Systems: Development, Characterization of Intratumoral Transport and ModelingSuh, SeungBeum (Virginia Tech, 2017-08-17)Systemic chemotherapy is a major therapeutic approach for nearly all types and stages of cancer. Success of this treatment depends not only on the efficacy of the therapeutics but also on the transport of the drug to all tumor cells in sufficient concentrations. Intratumoral drug transport is limited by characteristics of the tumor microenvironment such as elevated interstitial pressure and sparse, irregular vascularization. Moreover, poor tumor selectivity, leads to systemic toxicity. Bacteria possess a host of characteristics that address the aforementioned challenges in conventional drug delivery approaches including tumor selectivity, preferential tumor colonization, effective tumor penetration, which can be augmented via genetic engineering. However, in clinical trials conducted to date, bacteria have rarely been able to inhibit tumor growth solely by their presence in the tumor. The overall goal of this doctoral dissertation is to develop a novel tumor treatment system based on Salmonella Typhimurium VNP20009 (genetically modified for preferential tumor colonization and attenuation) coupled with biodegradable copolymer, poly(lactic-co-glycolic acid) nanoparticles, hereafter referred to as NanoBEADS (Nanoscale Bacteria Enabled Autonomous Drug Delivery System). To this end, a NanoBEADS fabrication procedure that is robust and repeatable was established and a microfluidic chemotaxis-based sorting platform for the separation NanoBEADS from unattached nanoparticles was developed. The transport efficacy of NanoBEADS compared to the commonly used passively-diffusing nanoparticle was investigated in vitro and in vivo and the intratumoral penetration of the therapeutic vectors was quantified using a custom image processing algorithm. The mechanism of intratumoral penetration was elucidated through 2D and 3D invasion assays. Lastly, we developed a biophysical model of intratumoral transport of NanoBEADS based on the intratumoral penetration experimental results towards the theoretical evaluation of the drug transport profile following the administration of NanoBEADS.
- The Biological and Immunological Effects of Irreversible Electroporation and Combination Therapy Options for the Improving the Treatment of Pancreatic CancerBrock, Rebecca Michaela (Virginia Tech, 2020-06-05)While cancer treatments have advanced for multiple cancers, pancreatic cancer remains a lethal cancer with few therapy options available. This is due to the inaccessibility of the tumor by surgical and thermal ablative means, high potential for chemoresistance and metastasis, and strongly immunosuppressive tumor microenvironment that makes new treatment measures ineffective in clinic. Irreversible electroporation (IRE) utilizes short, high voltage electrical pulses to form microlesions in cell membranes and induce cell death. While IRE has had significant impact in pancreatic cancer treatment in clinical trials, little is known on the biological and immunological effects of IRE on pancreatic cancer. By studying the effects of IRE on pancreatic tumor biology and the host immune system, I hypothesize I can identify potential combination therapy targets for IRE. I utilized in vitro, ex vivo, and in vivo animal models of both human and murine cancer to study the effects of IRE on pancreatic cancer progression and its potential for immunomodulation. My findings have shown that IRE can significantly delay cancer progression by inducing necroptosis in the tumor and altering the tumor microenvironment by increasing inflammatory signaling. IRE can also produce viable antigens for presentation to induce local and systemic immunosurveillance. However, these effects are limited by countering expression of programmed-cell death ligand 1 (PD-L1), a checkpoint protein that inhibits cytotoxic lymphocyte activity and allows the tumors to recur. The effects of IRE can therefore be expanded by multiple combination therapy approaches, such as chemotherapeutic application (potentially with nanoparticle packaging), PD-1/PD-L1 antibody immunotherapies, and small molecule inhibitors directed at tumor growth signaling that previously showed limited efficacy in clinic.
- Canine tonsillar squamous cell carcinoma - a multi-centre retrospective review of 44 clinical casesMas, A.; Blackwood, L.; Cripps, P.; Murphy, S.; de Vos, J.; Dervisis, Nikolaos G.; Martano, M.; Polton, G. A. (Wiley-Blackwell, 2011-07-01)OBJECTIVES: To review the presenting clinical signs, treatment and survival of dogs with tonsillar squamous cell carcinoma and, if possible, to identify useful prognostic indicators. METHODS: Medical records of 44 dogs were reviewed retrospectively. Clinical signs, clinical stage, time of diagnosis, treatment and outcome were recorded. Data were analysed using the Kaplan-Meier, logrank, Student’s t test, Kruskal-Wallis test and Chi-square/Fisher Exact test as appropriate. RESULTS: The most frequent clinical signs were cough (12 dogs, 27%), enlarged lymph nodes (11 dogs, 25%) and dysphagia (11 dogs, 25%). Anorexia and lethargy were less common but were significantly associated with a poor outcome. No matter what treatment modalities were used, survival times were short and median survival time for all the dogs in the study was 179 days. However, there were a small number of long-term survivors. CLINICAL SIGNIFICANCE: Dogs with tonsillar squamous cell carcinoma that suffered anorexia and lethargy had shorter survival times than patients without these clinical signs. Although surgery, chemotherapy and radiotherapy seem to increase the median survival time of dogs diagnosed with tonsillar squamous cell carcinoma, there is no highly effective treatment for canine tonsillar squamous cell carcinoma.
- Clinical outcomes in dogs with localized splenic histiocytic sarcoma treated with splenectomy with or without adjuvant chemotherapyLatifi, Max; Tuohy, Joanne L.; Coutermarsh-Ott, Sheryl; Klahn, Shawna L.; Leeper, Haley; Dervisis, Nikolaos G. (Wiley, 2020-09-28)Background: Localized splenic histiocytic sarcoma (HS) in dogs is a poorly understood disease, and could have longer survival times than disseminated or hemophagocytic HS. Understanding the clinical behavior of localized splenic HS can refine treatment recommendations. Objective: To describe the clinical characteristics and outcomes of dogs with localized splenic HS. Animals: Fourteen client-owned dogs with histologically confirmed splenic HS that received splenectomy. Methods: Multi-institutional retrospective case series—medical records of dogs with splenic HS were reviewed. Dog signalment, clinicopathologic data, primary and adjuvant treatments, and outcomes were obtained. Survival data were calculated using Kaplan-Meier analysis. Dog variables such as age, weight, platelet counts were reported using descriptive statistics. The Cox proportional hazards regression method was used to determine whether potential risk factors (weight, age, albumin level, hematocrit, and platelet count) were associated with PFI. Results: Median survival time for the dogs in this study was 427 days. Twelve dogs received adjuvant lomustine-based chemotherapy. Five dogs (35.7%) were suspected or confirmed to have developed metastatic disease. Eleven dogs died of disease, 1 dog died of unrelated cause, and 2 dogs were alive at final follow-up. Conclusions and Clinical Significance: Histiocytic sarcoma in dogs can manifest as a localized form in the spleen. Dogs with localized splenic HS treated with surgery ± chemotherapy can experience survival times over a year.
- Clinical prognostic factors in canine histiocytic sarcoma.Dervisis, Nikolaos G.; Kiupel, M.; Qin, Q.; Cesario, L. (2016-06-23)Canine histiocytic sarcoma (HS) is an aggressive neoplasia with variable clinical course and fatal outcome. The goals of this study were to evaluate a large cohort of canine patients with immunohistochemically confirmed HS and identify clinical prognostic factors. Biopsy submissions to the Michigan State University with tentative HS diagnoses were histologically and immunohistochemically confirmed, medical records collected, and interviews with relevant veterinary clinics conducted. Of 1391 histopathology submissions with a diagnosis containing the word ‘histiocytic’, 335 were suspicious for malignancy, and 180 were consistent with HS and had adequate clinical information recorded. The most commonly represented breeds were Bernese mountain dogs (n=53), labrador retrievers (n=26) and golden retrievers (n=17). Median survival for all dogs in the study was 170 days, and subgroup analysis identified palliative treatment, disseminated HS, and concurrent use of corticosteroids as statistically significant negative factors for survival, in both uni- and multi-variate methodologies.
- Clinicopathologic Significance of Histologic Grade, Pgp, and P53 Expression in Canine LymphomaDhaliwal, Ravinder S.; Kitchell, Barbara E.; Ehrhart, E. J.; Valli, Victor E.; Dervisis, Nikolaos G. (American Animal Hospital Association, 2013-05-01)To characterize the expression of P-glycoprotein (Pgp) and p53 in different histologic grades of canine multicentric lymphosarcoma (LSA), 31 cases of LSA without prior treatment were studied. The expression levels of the Pgp and p53 proteins were evaluated for their clinicopathologic significance among standard histologic evaluation. Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded archival samples of 31 previously untreated LSA cases to detect the expression of Pgp and p53. All dogs were subsequently treated with a combination chemotherapy protocol. Remission and survival durations were evaluated for correlation with histologic grade and presence of drug resistance markers. Of the 31 cases, 24 (80%) and 7 (22%) were positive for Pgp and p53, respectively. Overall, the median survival and duration of remission in the study was 246 days and 137 days, respectively. The National Cancer Institute working formulation histologic grade was not associated with either survival or duration of first remission (DOR). The Pgp protein expression and DOR and survival was not statistically significant. Expression of p53 was statistically correlated with survival.
- Combined Gemcitabine and Carboplatin Therapy for Carcinomas in DogsDominguez, Pedro A.; Dervisis, Nikolaos G.; Cadile, Casey D.; Sarbu, L.; Kitchell, B. E. (Wiley-Blackwell, 2009-01-01)Background: Response and adverse reactions to combined gemcitabine (GEM) and carboplatin (CARBO) therapy in dogs with carcinomas are not documented. Hypothesis: GEM and CARBO are safe for the treatment of dogs with carcinomas. Animals: Thirty-seven dogs with histologically or cytologically confirmed carcinomas. Methods: Prospective clinical trial. Dogs were treated with GEM (2 mg/kg, 20–30-minute infusion IV) on Days 1 and 8 and 4 hours later, CARBO (10 mg/kg IV) on Day 1. The cycle was repeated on Day 22. Results: Thirty-seven dogs (29 with measurable tumor) received a median of 2 cycles (range 0.5–6) for a total of 101 cycles administered. Twelve dogs (32%) developed neutropenia (3 Grade 3, and 5 Grade 4) and 9 (24%) thrombocytopenia (2 Grade 3, and 1 Grade 4). Dogs 420 kg were twice as likely to develop thrombocytopenia (P 5 .023). Twenty-seven dogs (73%) had evidence of gastrointestinal (GI) toxicosis, but most signs were of mild to moderate severity and self-limiting. One dog died of treatment-related complications. Overall tumor response rate was 13%. One dog with metastatic prostatic carcinoma achieved a complete remission and 1 dog with intestinal adenocarcinoma and 1 with tonsillar squamous cell carcinoma achieved partial remission. Twelve dogs achieved stable disease for a median of 72 days. Conclusion and Clinical Importance: GEM and CARBO combination causes mild to moderate hematologic and GI toxicosis in dogs with carcinoma. Response rate in this study was modest, and optimization of dosing of this combination is required.
- Diffusion Weighted MR Imaging in the Differentiation between Metastatic and Benign Lymph Nodes in Canine Patients with Head and Neck DiseaseStahle, Jessica Anne (Virginia Tech, 2016-07-14)In dogs with large primary tumors, regional lymph node involvement or evidence of distant metastasis can have worse prognoses and significantly decreased survival. Lymph node size alone has been shown to be insufficient as a predictor for the accurate clinical staging of some canine neoplasia, including oral malignant melanoma. However, regional lymph nodes of the oral cavity, such as the medial retropharyngeal lymph nodes, are difficult to access for routine sampling. Diffusion weighted magnetic resonance imaging (DWI) has demonstrated the ability to differentiate metastatic from inflammatory/benign lymph nodes in clinical studies with human cancer patients through the calculation of quantitative values of diffusion termed apparent diffusion coefficients (ADC). The objective of this exploratory study was to evaluate DWI and ADC as potential future methods for detecting malignant lymph nodes in dogs with naturally occurring disease. We hypothesized that DWI would identify significantly different ADC values between benign and metastatic lymph nodes in a group of canine patients with head or neck disease. Our results demonstrated that two of four observers identified a significant difference between the mean ADC values of the benign and metastatic lymph nodes. When data from all four observers were pooled, the difference between the mean ADC values of the benign and metastatic lymph nodes approached but did not reach significance (P-value: 0.0566). Therefore, our hypothesis was not supported. However, DWI does show promise in its ability to differentiate benign from metastatic lymph nodes, and further studies with increased patient numbers are warranted
- Efficacy of temozolomide or dacarbazine in combination with an anthracycline for rescue chemotherapy in dogs with lymphomaDervisis, Nikolaos G.; Dominguez, Pedro A.; Sarbu, Luminita; Newman, Rebecca G.; Cadile, Casey D.; Swanson, Christine N.; Kitchell, Barbara E. (American Veterinary Medical Association, 2007-08-15)Objective: To compare results of treatment with temozolomide or dacarbazine, in combination with an anthracycline, in dogs with relapsed or refractory lymphoma. Design: Nonrandomized, controlled clinical trial. Animals: 63 dogs with relapsed or refractory lymphoma. Procedures: Chemotherapy was administered in 21-day cycles. A combination of temozolomide and an anthracycline (doxorubicin or dactinomycin) was administered to 21 dogs and a combination of dacarbazine and an anthracycline was administered to 42 dogs. Efficacy and toxicoses were assessed. Results: Thirteen of the 18 (72%) dogs treated with the temozolomide-anthracycline combination and 25 of the 35 (71%) dogs treated with the dacarbazine-anthracycline combination had a complete or partial response. Median duration of response to rescue chemotherapy was 40 days (range, 0 to 217 days) for dogs in the temozolomide group and 50 days (range, 0 to 587 days) for dogs in the dacarbazine group. The incidence of high-grade hematologic toxicoses was significantly higher among dogs in the dacarbazine group than among dogs in the temozolomide group, but the incidence of gastrointestinal tract toxicoses was not significantly different between groups. There were no significant differences between groups in regard to proportion of dogs with a complete or partial response, duration of response to rescue chemotherapy, survival time following rescue chemotherapy, or overall survival time. Conclusions and Clinical Relevance: Both combinations had promise in the treatment of dogs with relapsed or refractory lymphoma, although administration of temozolomide was more convenient than administration of dacarbazine and caused fewer hematologic toxicoses.
- Elucidating the Role of Pattern Recognition Receptors in Understanding, Treating, and Targeting CancerScaia, Veronica Marie (Virginia Tech, 2019-04-23)Pattern Recognition Receptors (PRRs) are a group of evolutionarily conserved and germline-encoded cellular receptors of the innate immune system that are responsible for recognizing and responding to the entirety of the pathogens a host encounters. The ingenuity of the innate immune system is that with a comparatively miniscule pool of receptors, these receptors are capable of responding to a diverse and large array of pathogens and damage signals. Two highly relevant subsets of PRRs include nucleotide binding domain leucine rich repeat containing (NOD-like) receptors (NLRs) and Toll-like receptors (TLRs). Both NLRs and TLRs have been implicated in several diseases, including autoimmune disorders, inflammatory conditions, and cancer. Mice lacking a specific NLR, NLRP1, are more susceptible to chemically induced colitis and colitis-associated tumorigenesis. We investigated whether the absence of NLRP1 in the gastrointestinal tract influenced the composition of the microbiome, and whether it was responsible for the predisposition of these animals to colitis-associated cancer. By carefully controlling for non-genotype influences, we found that in fact maternal and housing factors were greater predictors over genotype of gut flora composition. This study concluded with a clearer understanding of NLRP1. We next investigated the effectiveness of a novel tumor ablation therapy, termed High-Frequency Irreversible Electroporation (H-FIRE) in a murine model of triple negative breast cancer. The chosen 4T1 model closely mimics aggressive human metastatic triple negative breast cancer, and metastasizes to the same organs. After ablation of the primary mammary tumor, we saw significant improvements in disease burden and metastases, both of which were accompanied by PRR activation within the tumor microenvironment, implicating PRRs in the successful treatment outcome following H-FIRE ablation. Lastly, we generated novel CRISPR-Cas9 plasmids to genetically manipulate the Tlr4 gene of wild type C57Bl/6 mice in order to recapitulate the LPS-hyporesponsive TLR4 protein of C3H/HeJ mice. This proof-of-concept study successfully demonstrated that PRRs can be targets for gene editing purposes, and that nanoparticle delivery leads to enhanced and improved delivery. Collectively, this work attempts to better appreciate the role of PRRs in understanding, treating, and targeting cancer.
- Evaluation and comparison of outcomes in dogs with periarticular and nonperiarticular histiocytic sarcomaKlahn, Shawna L.; Kitchell, Barbara E.; Dervisis, Nikolaos G. (American Veterinary Medical Association, 2011-07-01)Objective—To evaluate and compare the outcomes of dogs with periarticular histiocytic sarcoma (PAHS) and histiocytic sarcoma of other anatomic locations (non-PAHS) and identify factors associated with outcome for dogs with PAHS. Design—Retrospective cohort study. Animals—19 dogs with PAHS and 31 dogs with non-PAHS. Procedures—Medical records of dogs with histiocytic sarcoma that underwent definitive local treatment (surgery or radiation), chemotherapy, or a combination of these were reviewed. Patient signalment, clinical signs, staging test results, clinicopathologic data, type of treatment, response, and outcome were collected, and potential risk factors in dogs with PAHS were identified and analyzed for an association with outcome. Results—Dogs with PAHS lived significantly longer than did dogs with non-PAHS, with an overall median survival times of 391 (range, 48 to 980) and 128 (range, 14 to 918) days, respectively, despite the presence of suspected metastasis at diagnosis in 13 of 19 dogs with PAHS. Dogs with PAHS without evidence of metastasis at diagnosis lived significantly longer than did dogs with PAHS with evidence of metastasis, with median survival times of 980 (range, 83 to 980) and 253 (range, 48 to 441) days, respectively. Administration of prednisone in dogs with PAHS was associated with a significantly shorter time to tumor progression (TTP) and increased risk of tumor progression and death. Conclusions and Clinical Relevance—Results indicated that dogs with PAHS may have a favorable outcome independent of metastatic status when treated with chemotherapy or aggressive multimodal treatment. The concurrent administration of prednisone may be a negative predictive factor for survival time and TTP in dogs with PAHS.
- Evaluation of ifosfamide salvage therapy formetastatic canine osteosarcomaBatschinski, K.; Dervisis, Nikolaos G.; Kitchell, Barbara E. (Wiley-Blackwell, 2014-12-01)A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m−2 (median dose 375 mg m−2), with a median of two doses administered per dog (range 1–7 doses). The overall response to ifosfamide was 11.8% [complete response (CR)=1/17, partial response (PR)=1/17, stable disease (SD)=2/17, progressive disease (PD)=13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed.
- Evaluation of the therapeutic potential of Akt inhibition in a translational model of histiocytic sarcomaQin, Qizhi (Virginia Tech, 2018-10-12)Histiocytic sarcoma (HS) is an exceptionally rare malignant neoplasm derived from dendritic cells and histiocytes, with no available effective treatment options. Akt signaling and proteasome dysfunction have been implicated in the pathogenesis of the disease, both in humans and dogs. Our work aims to investigate the importance of the Akt signaling pathway and evaluate the potential of Akt-targeted therapy in a canine model of histiocytic sarcoma. We demonstrated Akt signaling to be active in 9 out of 10 canine HS tumor samples, regardless the presence of PTEN. Moreover, the Akt signaling pathway appears to be constitutively active in DH82 cells — a cell line model of canine HS, when compared to control canine dendritic cells. Pharmacologic Akt inhibition resulted in significant decrease in Akt S473 phosphorylation, GSK-3β S9 phosphorylation, Akt activity, cell viability, increased apoptosis, and resulted in sensitization to proteasome inhibition-depended cell death in a synergistic manner. Proteasome inhibition using carfilzomib, an irreversible proteasome inhibitor, induced dose-depended/caspase-3 independent cell death, at clinically relevant drug concentrations. The therapeutic effect of Akt inhibition was validated in vivo using a DH82 xenograft murine model. Akt inhibition lead to reduced tumor growth, prolonged overall survival, and ameliorated splenomegaly, but not affected the lung metastasis. Moreover, the therapeutic effect of Akt inhibition was potentiated in combination with carfilzomib. In conclusion, targeting Akt signaling may represent an attractive potential therapeutic target for the HS. Future studies are required to examine the clinical efficacy of Akt-targeted therapy in dogs with HS using novel selective Akt inhibitors.
- Evaluation of Tumor Grade and Proliferation Indices before and after Short-Course Anti-Inflammatory Prednisone Therapy in Canine Cutaneous Mast Cell Tumors: A Pilot StudyKlahn, Shawna L.; Dervisis, Nikolaos G.; Lahmers, Kevin K.; Benitez, Marian (MDPI, 2022-06-07)Glucocorticoid administration is a common clinical practice that attempts to decrease the inflammation associated with and improve the resectability of canine mast cell tumors (MCTs). However, the impact of neoadjuvant glucocorticoids on the histological features and proliferation indices of canine MCTs is unknown. The objective of this study was to evaluate changes in tumor grade, mitotic count, Ki67, AgNOR, and AgNORxKi67 scores following short-course anti-inflammatory neoadjuvant prednisone in canine patients with MCTs. This was a prospective single-arm pilot study. Client-owned dogs with treatment-naïve cytologically confirmed MCTs were enrolled. Patients underwent an initial incisional biopsy followed by a 10–14-day course of anti-inflammatory prednisone and surgical resection. All histological samples were randomized, masked, and evaluated by a single pathologist. Unstained paired pre- and post-treatment samples were submitted to a commercial laboratory for Ki67 and AgNOR immunohistochemical analysis. There were 11 dogs enrolled with 11 tumors. There were no statistical differences between the pre- and post-treatment histological parameters of mitotic index, Ki67, AgNOR, or Ki67xAgNOR. There were no clinically significant alterations between pre-treatment and post-treatment in the assignment of tumor grades. A short course of anti-inflammatory prednisone does not appear to alter the histological parameters that affect grade determination or significantly alter the proliferation indices in canine MCTs.
- Feline Obesity: Food Toys and Owner Perceived Quality of Life During a Prescribed WeightDodd, Lauren (Virginia Tech, 2019-09-12)The prevalence of overweight and obesity in the feline population is estimated to be 25.7% and 33.8%, respectively. Feline obesity is associated with comorbidities such as insulin resistance and hepatic lipidosis. Several risk factors are associated with obesity including middle age, neuter status, decreased activity, and diet. Obesity management is multifaceted and includes client education, diet modification, and consistent monitoring. Successful obesity management may be dependent on owner perception of their cat's quality of life during a prescribed weight loss plan. Poor quality of life perception may result in failure to complete the weight loss process. Food toys may be used to enhance environmental enrichment, allow cats to express their natural predatory behavior and overall improve owner-perceived quality of life. Therefore, we set out to investigate the role of food toys in owner-perceived quality of life of obese cats during a prescribed weight loss plan. Fifty-five cats with a BCS > 7 were enrolled in a double-blinded weight loss study and randomized into one of two groups: food toy (n=26) or food bowl (n=29). Each cat was provided a prescribed weight loss diet and instructions. Body weight and body condition score were evaluated monthly. Additionally, owners completed a monthly questionnaire to assess their cat's quality of life. Of the 44 cats in the final analysis, 66% (n=29) successfully completed the study and lost > 2 BCS points and/or achieved an ideal BCS of 5/9. Low-calorie vegetables were offered to the majority of cats (n= 32) due to owner reports of disruptive food seeking behavior. Of the cats offered vegetables, 87.5% (n=28) cats required a commercial palatant to consume the vegetables. All enrolled cats had a higher (p<0.0000) owner-perceive quality of life at the final visit/recheck/end of study (median QOL=110.0), as compared to the initial weight loss appointment (median QOL=126.0). The increase in quality of life was primarily driven by improvement in moving from one place to another, grooming and scratching, engaging in social activities, and playing and hunting. There was no effect (p=0.27) of food toy on owner-perceived quality of life. Prescribed weight loss improves owner-perceived quality of life of obese cats. A single food toy (ball-style) was included in this study and did not appear to influence owner-perceived QOL. However, the role of food toys needs further investigation as there are several food toy styles that have not yet been investigated during a prescribed weight loss plan. We suspect that most/all of the 32 cats fed vegetables would have withdrawn from the study. Therefore, including vegetables in the prescribed weight loss plan appears to improve success of weight loss in obese cats.
- Geographical differences in survival of dogs with non-Hodgkin lymphoma treated with a CHOP based chemotherapy protocolWilson-Robles, H.; Budke, C. M.; Miller, T.; Dervisis, Nikolaos G.; Novosad, A.; Wright, Z.; Thamm, D. H.; Vickery, K.; Burgess, K.; Childress, M.; Lori, J.; Saba, C.; Rau, S.; Silver, M.; Post, G.; Reeds, K.; Gillings, S.; Schleis, S.; Stein, T.; Brugmann, B.; DeRegis, C.; Smrkovski, O.; Lawrence, J.; Laver, T. (Blackwell, 2017-04-17)Background: In humans geographical differences in the incidence and presentation of various cancers have been reported. However, much of this information has not been collected in veterinary oncology. Aims: The purpose of this study was to determine if a geographic difference in progression free survival exists for dogs with lymphoma treated within the US. Materials and Methods: Medical records of 775 cases of canine lymphoma from 3 US regions (west, south and north), treated with CHOP chemotherapy, were retrospectively evaluated. Cases were collected from referral institutions and were required to have received at least one doxorubicin treatment and have follow up information regarding time to progression. Results: Significant differences in sex (p = 0.05), weight (p = 0.049), stage (p < 0.001), immunophenotype (p = <0.001), and number of doxorubicin doses (p = 0.001) were seen between regions. Upon univariate analysis, progression free survival (PFS) differed by region (p = 0.006), stage (p = 0.009), sub-stage (p = 0.0005), and immunophenotype (p = 0.001). A multivariable Cox regression model showed that dogs in the western region had a significantly shorter PFS when compared to the south and east. Conclusions: PFS was significantly affected by stage, sub-stage and phenotype.
- Hemophagocytic syndrome in a catWilkinson, Ashley R.; Carr, Susan V.; Klahn, Shawna L.; Dervisis, Nikolaos G.; Hanks, Cory R. (SAGE, 2018-07)Case summary: A 12-year-old male castrated domestic shorthair cat was evaluated for a 10 month history of weight loss. Thin body condition and a grade II/VI systolic parasternal heart murmur was noted during examination. Moderate-to-severe anemia and intermittent thrombocytopenia were identified on serial complete blood counts. Antibodies against feline immunodeficiency virus (FIV) were detected, but vaccination for FIV occurred previously. Echocardiography revealed biatrial and biventricular enlargement, left ventricular hypertrophy and pericardial effusion. Splenomegaly was present on abdominal ultrasound and cytological evaluation revealed macrophagic infiltration with erythrophagocytosis. Cytological evaluation of the bone marrow revealed similar findings. Histopathology of the spleen confirmed hemophagocytosis with no evidence of malignancy. A presumptive diagnosis of hemophagocytic syndrome was made. PCR testing for FIV on the splenic tissue was negative. The cat was treated with lomustine. Disease progression occurred approximately 6 months after diagnosis and the cat was euthanized. Relevance and novel information: To our knowledge, this is one of the few reports describing the diagnosis of hemophagocytic syndrome in a cat.
- High intensity focused ultrasound for the treatment of solid tumors: a pilot study in canine cancer patientsCarroll, Jennifer; Coutermarsh-Ott, Sheryl; Klahn, Shawna L.; Tuohy, Joanne L.; Barry, Sabrina L.; Allen, Irving C.; Hay, Alayna N.; Ruth, Jeffrey; Dervisis, Nikolaos G. (Taylor & Francis, 2022-01)Purpose: To investigate the safety, feasibility, and outcomes of High-Intensity Focused Ultrasound (HIFU) for the treatment of solid tumors in a spontaneous canine cancer model. Methods: Dogs diagnosed with subcutaneous solid tumors were recruited, staged and pretreatment biopsies were obtained. A single HIFU treatment was delivered to result in partial tumor ablation using a commercially available HIFU unit. Tumors were resected 3-6 days post HIFU and samples obtained for histopathology and immunohistochemistry. Total RNA was isolated from paired pre and post treated FFPE tumor samples, and quantitative gene expression analysis was performed using the nCounter Canine IO Panel. Results: A total of 20 dogs diagnosed with solid tumors were recruited and treated in the study. Tumors treated included Soft Tissue Sarcoma (n = 15), Mast Cell Tumor (n = 3), Osteosarcoma (n = 1), and Thyroid Carcinoma (n = 1). HIFU was well tolerated with only 1 dog experiencing a clinically significant adverse event. Pathology confirmed the presence of complete tissue ablation at the HIFU targeted site and immunohistochemistry indicated immune cell infiltration at the treated/untreated tumor border. Quantitative gene expression analysis indicated that 28 genes associated with T-cell activation were differentially expressed post-HIFU. Conclusions: HIFU appears to be safe and feasible for the treatment of subcutaneous canine solid tumors, resulting in ablation of the targeted tissue. HIFU induced immunostimulatory changes, highlighting the canine cancer patient as an attractive model for studying the effects of focal ablation therapies on the tumor microenvironment.
- High-Frequency Irreversible Electroporation for Treatment of Primary Liver Cancer: A Proof-of-Principle Study in Canine Hepatocellular CarcinomaPartridge, Brittanie R.; O'Brien, Timothy J.; Lorenzo, Melvin F.; Coutermarsh-Ott, Sheryl; Barry, Sabrina L.; Stadler, Krystina L.; Muro, Noelle; Meyerhoeffer, Mitchell; Allen, Irving C.; Davalos, Rafael V.; Dervisis, Nikolaos G. (2020-03)Purpose: To determine the safety and feasibility of percutaneous high-frequency irreversible electroporation (HFIRE) for primary liver cancer and evaluate the HFIRE-induced local immune response. Materials and Methods: HFIRE therapy was delivered percutaneously in 3 canine patients with resectable hepatocellular carcinoma (HCC) in the absence of intraoperative paralytic agents or cardiac synchronization. Pre- and post-HFIRE biopsy samples were processed with histopathology and immunohistochemistry for CD3, CD4, CD8, and CD79a. Blood was collected on days 0, 2, and 4 for complete blood count and chemistry. Numeric models were developed to determine the treatment-specific lethal thresholds for malignant canine liver tissue and healthy porcine liver tissue. Results: HFIRE resulted in predictable ablation volumes as assessed by posttreatment CT. No detectable cardiac interference and minimal muscle contraction occurred during HFIRE. No clinically significant adverse events occurred secondary to HFIRE. Microscopically, a well-defined ablation zone surrounded by a reactive zone was evident in the majority of samples. This zone was composed primarily of maturing collagen interspersed with CD3(+)/CD4(-)/CD8(-) lymphocytes in a proinflammatory microenvironment. The average ablation volumes for the canine HCC patients and the healthy porcine tissue were 3.89 cm(3) +/- 0.74 and 1.56 cm(3) +/- 0.16, respectively (P = .03), and the respective average lethal thresholds were 710 V/cm +/- 28.2 and 957 V/cm +/- 24.4 V/cm (P = .0004). Conclusions: HFIRE can safely and effectively be delivered percutaneously, results in a predictable ablation volume, and is associated with lymphocytic tumor infiltration. This is the first step toward the use of HFIRE for treatment of unresectable liver tumors.
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