Re-examining poikilocytosis in goats: prevalence, type and association with age and disease

BackgroundDomestic goats (Capra aegagrus hircus) are a food, fiber and companion animal. Abnormal erythrocyte shapes (poikilocytes) are considered normal in young goats, but their association with disease is not well described. Likewise, there is little information on the significance of poikilocytosis in adult goats.ObjectiveThe objective of this study was to investigate the prevalence, severity and type of poikilocytosis in young and adult goats and its association with age, sex, breed, laboratory results, and underlying disease.MethodsWe retrospectively examined clinical and laboratory data from 1254 goats presented at the University of California-Davis Veterinary Medical Teaching Hospital from 1997 to 2019. We analyzed 313 blood smears from goats with moderate or marked (MOD-MKD) poikilocytosis on initial blood smear evaluation. Number and type of poikilocytes per 1000 red blood cells (RBCs) were enumerated. Laboratory values and primary disease categories were compared with the severity and type of poikilocytosis.ResultsKids (<6 mos) and juveniles (>6 mos to <1 year) had a higher prevalence of MOD-MKD poikilocytosis (95/210, 45.2% kids; 27/59, 45.8% juveniles) than adult goats (≥1 year; 190/982, 19.3%) (p < 0.001). Kids had a higher percentage of elliptocytes, dacryocytes, and schistocytes and a lower percentage of polygonal and spiculated RBCs than juvenile and adult goats (p < 0.001). Of goats with MOD-MKD (vs NONE-SLIGHT) poikilocytosis, kids had lower HGB and MCH, and higher RDW (p ≤ 0.02); juveniles and adult goats had lower HCT, MCV, MCH, and albumin concentration (p ≤ 0.01), and all age groups had lower total CO2 concentration and higher PLT counts (p < 0.03). Adult goats with MOD-MKD poikilocytosis also had higher BUN:Cr ratios (p = 0.005). Gastrointestinal parasitism, Johne’s disease, diarrhea/enteritis, lice, hepatic disease and renal disease (but not urolithiasis) were significantly associated with MOD-MKD poikilocytosis (p < 0.001). Goats with hepatic and renal disease had a higher prevalence and percentage of spiculated cells (p = 0.001). Goats with Johne’s disease had a higher prevalence of polygonal cells (93.3%) and dacryocytes (66.7%) than other diseases, and elliptocytes predominated in a higher proportion (36.0%) of adult goats with GI parasitism vs other diseases (p < 0.05).ConclusionThese findings suggest that iron deficiency is an important pathophysiologic mechanism of poikilocytosis in juvenile and adult goats, and possibly in kids, whether due to iron-restricted erythropoiesis, chronic hemorrhage, functional iron deficiency, or a combination of these mechanisms. Further investigation into the detection and monitoring of iron deficiency and the value of poikilocytosis as a diagnostic marker of iron status in goats is warranted

Comparative Pathology and Androgen Receptor Signaling of Prostate Cancer in Dogs

Prostate cancer (PCa) is the most common cancer in men. While initial treatments involve androgen deprivation therapies and targeting the androgen receptor (AR), a subset of patients eventually develop aggressive forms of PCa resistant to these treatments, leaving them with limited therapeutic options. Because of this, there is a critical need to identify an animal model that recapitulates the advanced stages of human PCa to facilitate the development of novel, effective therapeutics. Dogs present a unique opportunity as they naturally develop aggressive AR null PCa, resembling advanced human PCa. However, to effectively leverage dogs as models, it is essential to discern which animals are suitable for preclinical trials ante-mortem and understand the pathophysiology of androgen receptor signaling in dog PCa. In this study, we examined the clinicopathologic features of PCa in dogs to identify characteristics indicative of prostatic adenocarcinoma (PRAD), the most prevalent subtype in humans, compared to other types such as prostatic transitional cell carcinoma (P-TCC) in order to identify animals appropriate for preclinical trials. Our findings revealed associations between specific clinicopathologic features and different PCa subtypes in dogs, including strong association of hypoalbuminemia with PRAD and the presence of Melamed-Wolinska bodies and necrosis on cytology specimens with P-TCC. Additionally, we explored the red blood cell distribution width to albumin (RAR) ratio as a potential diagnostic marker to differentiate between PRAD and P-TCC, demonstrating its utility when a certain cut-off ratio was applied. Furthermore, we conducted a proof-of-concept study to investigate the outcomes of reconstituting AR signaling in AR null PRAD dog cell lines. We aimed to determine whether restoring AR signaling in these dog cell lines attenuates aggressive behaviors, as observed in human PCa cell lines. Our results showed varied responses across different cell lines, with AR signaling leading to the abrogation of aggressive behaviors in some cell lines resembling androgen-dependent PCa, while inciting more aggressive behavior in others resembling castration-resistant prostate cancer (CRPC). Overall, this foundational research lays the groundwork for utilizing dogs as valuable models for studying human PCa progression and provides insights into selecting appropriate dog PCa cell lines for in vitro studies and identifying suitable dog PCa patients for preclinical trials for emerging therapeutics

Pericardial effusion in a dog due to T‐cell lymphoma of granular lymphocyte type

Pericardial effusions in dogs are most often diagnosed as haemorrhagic and idiopathic. Pericardial effusions secondary to an underlying neoplastic process are infrequently diagnosed, as neoplastic cells are rarely observed in a sample of the effusion. In the present report, we describe a 9-year-old dog with pericardial effusion due to T-cell lymphoma of granular lymphocyte type. Immunophenotyping and molecular clonality PCR were performed to confirm the cytologic diagnosis. To our knowledge, this is the first report of pericardial effusion in a dog due to T-cell lymphoma of granular lymphocyte type

Clinicopathologic Characterization of Prostatic Cancer in Dogs

Clinicopathologic data in dogs with prostate cancer (PCa) may aid in the differentiation between tumor types and subsequent treatment decisions; however, these data are often unreported. Demographic, clinicopathologic, cytologic, histologic and survival data from dogs with primary prostatic adenocarcinoma (PRAD) (n = 56) and primary prostatic transitional cell carcinoma (P-TCC) (n = 74) were acquired from a tertiary veterinary teaching hospital from 1992 to 2022. Red blood cell distribution width (RDW) to albumin ratio (RAR) was evaluated for diagnostic utility in differentiating between PRAD and P-TCC. Sections from PRAD tumors (n = 50) were stained for androgen receptor (AR) expression, and laboratory data were compared between AR positive (AR+) and AR negative (AR−) groups. RDW was increased in PRAD, while albumin was decreased (p p p p > 0.05). In conclusion, hypoalbuminemia was significantly associated with PRAD and decreased survival, while MWB and necrosis were significantly associated with P-TCC on cytology. These clinicopathologic data may help clinicians differentiate between these tumors ante mortem to guide appropriate treatment and intervention

Clinicopathologic Characterization of Prostatic Cancer in Dogs

Clinicopathologic data in dogs with prostate cancer (PCa) may aid in the differentiation between tumor types and subsequent treatment decisions; however, these data are often unreported. Demographic, clinicopathologic, cytologic, histologic and survival data from dogs with primary prostatic adenocarcinoma (PRAD) (n = 56) and primary prostatic transitional cell carcinoma (P-TCC) (n = 74) were acquired from a tertiary veterinary teaching hospital from 1992 to 2022. Red blood cell distribution width (RDW) to albumin ratio (RAR) was evaluated for diagnostic utility in differentiating between PRAD and P-TCC. Sections from PRAD tumors (n = 50) were stained for androgen receptor (AR) expression, and laboratory data were compared between AR positive (AR+) and AR negative (AR-) groups. RDW was increased in PRAD, while albumin was decreased (p < 0.05). P-TCC was associated with Melamed-Wolinska bodies (MWB) and necrosis on cytology (p < 0.05). RAR had acceptable diagnostic utility in the differentiation of PCa tumors (AUC = 0.7; p < 0.05). Survival rates and metastases were equivocal. AR+ and AR- PRAD tumors did not differ in clinicopathologic data or survival (p > 0.05). In conclusion, hypoalbuminemia was significantly associated with PRAD and decreased survival, while MWB and necrosis were significantly associated with P-TCC on cytology. These clinicopathologic data may help clinicians differentiate between these tumors ante mortem to guide appropriate treatment and intervention

Molecular Similarities and Differences between Canine Prostate Cancer and Human Prostate Cancer Variants

Dogs are one of few species that naturally develop prostate cancer (PCa), which clinically resembles aggressive, advanced PCa in humans. Moreover, PCa-tumor samples from dogs are often androgen receptor (AR)-negative and may enrich our understanding of AR-indifferent PCa in humans, a highly lethal subset of PCa for which few treatment modalities are available This narrative review discusses the molecular similarities between dog PCa and specific human-PCa variants, underscoring the possibilities of using the dog as a novel pre-clinical animal model for human PCa, resulting in new therapies and diagnostics that may benefit both species

Molecular Similarities and Differences between Canine Prostate Cancer and Human Prostate Cancer Variants

Dogs are one of few species that naturally develop prostate cancer (PCa), which clinically resembles aggressive, advanced PCa in humans. Moreover, PCa-tumor samples from dogs are often androgen receptor (AR)-negative and may enrich our understanding of AR-indifferent PCa in humans, a highly lethal subset of PCa for which few treatment modalities are available This narrative review discusses the molecular similarities between dog PCa and specific human-PCa variants, underscoring the possibilities of using the dog as a novel pre-clinical animal model for human PCa, resulting in new therapies and diagnostics that may benefit both species

Optimization of eIF4E-Binding Peptide Pep8 to Disrupt the RBM38-eIF4E Complex for Induction of p53 and Tumor Suppression.

Interaction of RNA-binding protein RBM38 with eIF4E on p53 mRNA is known to suppress p53 mRNA translation, which can be disrupted by an 8-amino acid peptide (Pep8-YPYAASPA) derived from RBM38, leading to induction of p53 and tumor suppression. Here, we rationally designed multiple Pep8 derivatives and screened for their binding affinities towards eIF4E in silico. We showed that several key residues within Pep8 are necessary for its structure and function. We identified a shortened 7-amino acid peptide (Pep7-PSAASPV) that has the highest affinity towards eIF4E and is the most potent inducer of p53 expression. We found that iRGD is an effective vehicle to deliver Pep7 inside of cells for induction of p53 expression and growth suppression as compared to other cell penetrating peptides (Penetratin and Pep-1). We found that peptide cyclization enhances Pep8 affinity for eIF4E, induction of p53 and tumor cell growth suppression. We also found that the ability of Pep7 to induce p53 expression and growth suppression is conserved in cells derived from canine osteosarcoma, a spontaneous tumor model frequently used for testing the feasibility of a therapeutic agent for human cancer. Moreover, we showed that both human and canine osteosarcoma cells, which are notoriously resistant to radiation therapy, were sensitized by Pep7 to radiation-induced growth suppression and cell death. Together, our data suggest that Pep7 may be explored to sensitize tumors to radiation therapy