Computed tomographic characteristics of testicular teratoma in a cat.

A 5-year-old intact male mixed-breed cat weighing 4.5 kg was referred to our hospital with a left testicular mass. CT revealed mild heterogeneous contrast enhancement and calcification in the testicular mass. A well-defined, contrast-enhancing, multiloculated mass with fluid-filled areas was extended from the testicular mass in the scrotum to the caudal aspect of the left kidney. The abdominal mass extended to the right crus of the diaphragm, and the gastrointestinal tract was compressed dorsally. Histopathology was consistent with teratoma. Characteristic CT findings in a feline testicular teratoma may include calcification and cystic areas.

Liposome-encapsulated progesterone efficiently suppresses B-lineage cell proliferation.

Progesterone suppresses several ancient pathways in a concentration-dependent manner. Based on these characteristics, progesterone is considered a candidate anticancer drug. However, the concentration of progesterone used for therapy should be higher than the physiological concentration, which makes it difficult to develop progesterone-based anticancer drugs. We previously developed liposome-encapsulated progesterone (Lipo-P4) with enhanced anticancer effects, which strongly suppressed triple-negative breast cancer cell proliferation in humanized mice. In this study, we aimed to clarify whether Lipo-P4 effectively suppresses the proliferation of B-lineage cancer cells. We selected six B-cell lymphoma and two myeloma cell lines, and analyzed their surface markers using flow cytometry. Next, we prepared liposome-encapsulated progesterone and examined its effect on cell proliferation in these B-lineage cancer cells, three ovarian clear cell carcinoma cell lines, two prostate carcinoma cell lines, and one triple-negative breast cancer adenocarcinoma cell line. Lipo-P4 suppressed the proliferation of all cancer cell lines. All B-lineage cell lines, except for the HT line, were more susceptible than the other cell types, regardless of the expression of differentiation markers. Empty liposomes did not suppress cell proliferation. These results suggest that progesterone encapsulated in liposomes efficiently inhibits the proliferation of B-lineage cells and may become an anticancer drug candidate for B-lineage cancers.

Noonan Syndrome-related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review.

Noonan syndrome-related myeloproliferative disorder (NS/MPD) and juvenile myelomonocytic leukemia (JMML) are rare MPDs that occur in young children. We herein report a case of NS/MPD with neonatal onset. The patient had a characteristic appearance and high monocyte count in the peripheral blood and bone marrow. Genetic testing showed the E139D mutation in PTPN11 ; however, the patient did not meet all the diagnostic criteria for JMML, and we thus diagnosed him with NS/MPD. Eight other cases of NS/MPD with neonatal onset are also summarized. The initial presentation varied, and the prognosis was considered poor compared with previous reports of NS/MPD.

Fibrinogen Aα-chain amyloidosis outbreaks in Japanese squirrels (Sciurus lis): a potential disease model.

Fibrinogen Aα-chain amyloidosis is a hereditary systemic amyloidosis characterized by glomerular amyloid depositions, which are derived from the fibrinogen Aα-chain variant in humans. Despite its unique pathology, the pathogenic mechanisms of this disease are only partially understood. This is in part because comparative pathological studies on fibrinogen Aα-chain amyloidosis are currently unavailable as there is a lack of reported cases in animals other than humans. In this study, mass spectrometry-based proteomic analyses of Japanese squirrels (Sciurus lis) that died in five Japanese zoos showed that they developed glomerular-associated fibrinogen Aα-chain amyloidosis with an extremely high incidence rate (29/38 cases, 76.3%). The condition was found to be age-dependent in the Japanese squirrels, with 89% of individuals over 4 years of age affected. Mass spectrometry revealed that the C-terminal region of the fibrinogen Aα-chain was involved in amyloidogenesis in Japanese squirrels as well as humans. No gene variations were identified between amyloid-positive and amyloid-negative squirrels, which contrasted with the available data for humans. The results indicate that fibrinogen Aα-chain amyloidosis is a senile amyloidosis in Japanese squirrels. The results have also provided comparative pathological support that the amyloidogenic C-terminal region of the fibrinogen Aα-chain is involved in the characteristic glomerular pathology, regardless of the animal species. This study elucidates the potential causes of death in Japanese squirrels and will contribute to future comparative pathological studies of fibrinogen Aα-chain amyloidosis. © 2023 The Pathological Society of Great Britain and Ireland.

Cystatin C as a Potential Blood Biomarker for Sarcoidosis: A Case Report.

Sarcoidosis is a multi-organ medical condition that is characterized by the formation of granulomas. We aimed to identify a correlation between each sarcoidosis blood biomarker and cystatin C (Cys-C) in sarcoidosis patients. We report a case of a 60-year-old man with sarcoidosis. The correlation between his Cys-C and each blood biomarker level and that between each blood biomarker and serum creatinine levels were determined using linear regression. Serum Cys-C correlated with each blood biomarker of sarcoidosis, while creatinine did not. These findings suggest that Cys-C is a potential blood biomarker for sarcoidosis.

Simultaneous bilateral spontaneous pneumothorax in a patient with anorexia nervosa.

Anorexia nervosa causes various complications accompanying weight loss and malnutrition. Although bilateral spontaneous pneumothorax (SBSP) is uncommon, caution is needed in anorexia nervosa because this complication can be fatal. We encountered a 17-year-old girl with SBSP from emphysematous pulmonary changes due to anorexia nervosa. She was hospitalized with SBSP during treatment for anorexia nervosa. Chest tube drainage was started on admission, but no improvement was achieved. Surgery was therefore performed. Lung lesions on surgical specimens demonstrated malnutrition-induced emphysematous changes, a risk factor for SBSP. Attention should be paid to the occurrence of SBSP during the clinical course of anorexia nervosa.

Reconstruction of convex urethral stoma in a cat with prepubic urethrostomy.

An intact, male mixed-breed cat approximately 3 months of age was referred to Iwate University Veterinary Teaching Hospital with dysuria that developed after a traffic accident. At the initial visit, a cystostomy tube was placed as a temporal urinary diversion. Antegrade urethrography revealed severe stenosis of the intrapelvic urethra. A prepubic urethrostomy (PPU) with formation of a convex urethral stoma was performed 22 days after the first visit. Twenty-four months after surgery, the cat could urinate smoothly in a standing position, although a small amount of intermittent leakage was observed immediately after getting up. There was no evidence of peristomal dermatitis. Therefore, the formation of a convex urethral stoma may effectively prevent peristomal dermatitis in cats who undergo PPU.

Molecular design of near-infrared (NIR) fluorescent probes targeting exopeptidase and application for detection of dipeptidyl peptidase 4 (DPP-4) activity.

Monitoring the activities of proteases in vivo is an important requirement in biological and medical research. Near-infrared (NIR) fluorescent probes are particularly useful for in vivo fluorescence imaging, due to the high penetration of NIR and the low autofluorescence in tissue for this wavelength region, but most current NIR fluorescent probes for proteases are targeted to endopeptidase. Here, we describe a new molecular design for NIR fluorescent probes that target exopeptidase by utilizing the >110 nm blueshift of unsymmetrical Si-rhodamines upon amidation of the N atom of their xanthene moiety. Based on this molecular design, we developed Leu-SiR640 as a probe for leucine amino peptidase (LAP). Leu-SiR640 shows a one order of magnitude larger fluorescence increment (669-fold) upon reaction with LAP than existing NIR fluorescent probes. We similarly designed and synthesized EP-SiR640, a NIR fluorescent probe that targets dipeptidyl peptidase 4 (DPP-4). We show that this probe can monitor DPP-4 activity not only in living cells but also in mouse organs and tumors. This probe could also detect esophageal cancer in human clinical specimens, based on the overexpression of DPP-4 activity.

Diffuse FDG uptake in the bilateral lungs: hypersensitivity pneumonitis supported by low-dose CT findings.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease resulting from an immune-mediated response in susceptible and sensitized individuals to various inhaled antigens in the environment. Imaging diagnosis is usually based on high-resolution CT findings. Here, we present a 49-year-old man with a history of diffuse large B-cell lymphoma presented with fever and occasional cough. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed diffuse FDG uptake in the bilateral lungs. Expiratory low-dose CT simultaneously performed in PET scanning revealed centrilobular nodules and air trapping in ground glass opacities (GGO). Our imaging diagnosis was acute hypersensitivity pneumonitis (HP). Based on the results of his clinical course, blood laboratory tests, and bronchoscopy, he was diagnosed with acute HP. Diffuse pulmonary FDG uptake can be seen in the patients with acute HP. In addition, expiratory low-dose CT findings of centrilobular nodules and air trapping in GGO may be helpful for accurate diagnosis of acute HP.

[Investigation of the safety and usefulness of a renal biopsy for older elderly patients ≥75 years old].

AIM: We herein report the safety and usefulness of a kidney biopsy in older elderly patients (≥75 years old). METHODS: A retrospective observational study was conducted in older elderly patients who had received a renal biopsy at the Department of Nephrology, Shimane University Hospital, from January 1, 2008, to December 31, 2018. The native renal biopsy results of 52 later-stage elderly patients were analyzed (29 men and 23 women). RESULTS: The most common indication for a renal biopsy was nephrotic syndrome (n = 22), followed by rapidly progressive glomerulonephritis (n = 12) and asymptomatic urinary abnormalities (n = 12). The most common pathological diagnosis was membranous nephropathy (n = 12), followed by ANCA-associated nephritis (n= 8), minimal change nephrotic syndrome (6 case), membranoproliferative glomerulonephritis (n = 5), IgA nephropathy (n = 4), and diabetic nephropathy (n = 3). The concordance rate between the clinical and pathological diagnoses was 53.8%. The only complication of the renal biopsy was hemorrhaging requiring blood transfusion (1 patient; 1.9%). The hemoglobin level decreased by 0.5±0.05 d/dL after the biopsy. CONCLUSION: The rate of serious complications associated with a renal biopsy was comparable to that in previous reports in younger patient. Renal biopsies can therefore be safely performed even in older elderly patients. The concordance rate of the clinical and pathological diagnoses was about 50%. Therefore, renal biopsies should be performed in older elderly patients when necessary.

A Remarkable Elevation in the Procalcitonin Levels Due to Diabetic Ketoacidosis in a Hemodialysis Patient.

Procalcitonin (PCT), a marker of the inflammatory response during infections, can be elevated by diabetic ketoacidosis (DKA). A male patient in his 50s with diabetic nephropathy on hemodialysis presented with vomiting and a reduced level of consciousness and was diagnosed with DKA. His PCT level was markedly elevated, but bacterial cultures (blood, urine, and stool) were negative. The PCT level decreased after DKA improvement. In this patient, DKA probably enhanced the PCT levels. As DKA can increase the PCT levels, an elevation of the PCT levels in DKA patients may not be indicative of infectious diseases, and non-infectious causes of DKA should therefore be considered.

Assessment of tumor enhancement by contrast-enhanced CT in solid tumor-bearing dogs treated with toceranib phosphate.

In humans, contrast-enhanced CT (CECT) has been used to indirectly assess the antiangiogenic effects demonstrated by a number of tyrosine kinase inhibitors. This retrospective, cross-sectional study aimed to quantitatively evaluate changes in tumor contrast-enhancement (CE) using CECT in solid tumor-bearing dogs treated with toceranib phosphate (TOC). The changes in tumor size and CE were measured using the Hounsfield unit (HU) scale in CECT images before TOC treatment and between 30 and 90 days after initiating the treatment. Among the 36 dogs treated with TOC, eight (22.2%) showed a partial response, 22 (61.1%) showed stable disease, and six (16.7%) showed progressive disease. Thirty (83.3%) of 36 dogs showed a decrease in tumor CE (median: -20%, range: -1% to -48%) after initiating the treatment. The results indicated that tumor CE and size changes were observed in tumor-bearing dogs that were treated with TOC; however, tumor CE was not significantly correlated with tumor regression. We suggest that these results could serve as pilot data to evaluate the antiangiogenic effects associated with TOC.

Therapeutic strategies for elbow ankylosis due to heterotopic ossification in patients with severe burns.

BACKGROUND: Heterotopic ossification (HO) occurs frequently in the elbow in burn patients, and extends beyond the anatomical structure. HO of the elbow can cause joint contracture and adversely affect activities of daily living.Currently, there is no effective prophylaxis for HO as the precise underlying mechanism remains unknown. Therefore, there is no choice but to treat HO after it has developed. To date, however, no effective standard treatment has been reported, and therefore treatment methods vary between different facilities. Surgical resection is widely accepted as the only therapeutic option once HO limits functional mobility of the elbow. PURPOSES: Based on past reports, we examined our cases and recommend effective therapeutic strategies. We posed the following three questions: (1) Is the surgical intervention effective or detrimental for elbow ankylosis due to HO? (2) What is the best timing for the intervention? (3) What is the most effective postoperative rehabilitation plan? METHODS: We treated three patients with complete ankylosis of the elbow due to HO after severe burn injury using different protocols. RESULTS: Surgery was performed in two cases and rehabilitation therapy was commenced immediately from the first postoperative day. Both patients showed improvement in the active range of motion in their elbow joints. The other patient did not undergo surgery, and his elbows became fixed in the completely extension position. CONCLUSION: Surgical resection is beneficial for elbow ankylosis due to HO after burn injury. Although the exact surgical timing is still controversial, we recommend that surgery should be performed as soon as possible after improving the skin condition around the elbow and confirming the maturation of HO on radiographs. Early rehabilitation and pain control are also important after surgery.

Effects of combretastatin A-4 phosphate on canine normal and tumor tissue-derived endothelial cells.

Combretastatin A-4 phosphate (CA4P) selectively blocks tumor blood flow. However, the detailed mechanisms through which CA4P specifically affects tumor blood vessels are not well understood. Recent reports revealed that tumor tissue-derived endothelial cells (TECs) have various specific features in comparison with normal tissue-derived endothelial cells (NECs). Thus, abnormalities in TECs may be involved in the selective vascular blockade mechanism of CA4P. In this study, we evaluated the effects of CA4P on canine NECs and TECs using confocal microscopy. NECs exhibited different susceptibilities at subconfluence and at 100% confluence. In addition, inhibition of vascular endothelial cadherin (VE-cadherin) in NECs increased the sensitivity of the cells to CA4P. TECs seemed to be more susceptible to CA4P than NECs. The expression pattern of VE-cadherin in TECs was abnormal compared with that of NECs, suggesting that VE-cadherin may have functional abnormalities in these cells. Taken together, these results indicate that the tumor-vascular selectivity of CA4P may be related to VE-cadherin dysfunction in TECs.

Circulating microRNA-214 and -126 as potential biomarkers for canine neoplastic disease.

Circulating microRNAs in the blood may provide diagnostic and prognostic information about canine neoplastic diseases, and their profiles may be conserved between human and canine species. We performed RT-qPCR to obtain the profiles of circulating plasma microRNA-214 and -126 in total 181 cases of canine neoplastic diseases and healthy controls. MicroRNA-214 levels were high in 2 epithelial tumours (thyroid and mammary carcinomas) and 4 non-epithelial tumours (osteosarcoma, histiocytic sarcoma, chondrosarcoma, and hemangiosarcoma). In contrast, microRNA-126 levels were high in 6 epithelial tumours (mammary, hepatocellular, squamous cell, thyroid, transitional cell carcinomas, and adenocarcinoma) and 4 non-epithelial tumours (osteosarcoma, mast cell tumour, melanoma, and hemangiosarcoma). The diagnostic potential of microRNA-214 was relatively high in sarcomas, whereas that of microR-126 was high in most types of the tumours. MicroRNA-214 and -126 were prognostic predictors in 2 groups (adenocarcinoma and non-epithelial tumours except for osteosarcoma) and 3 groups (epithelial tumours, adenocarcinoma, and melanoma), respectively. Additionally, the microRNA levels did not show a strong correlation with the other clinical parameters. In conclusion, circulating microRNA-214 and -126 have the potential to be diagnostic and prognostic biomarkers for canine neoplastic diseases. Furthermore, their profiles may be key references as well for exploring novel biomarkers for human cancers.

Effects of inhibitors of vascular endothelial growth factor receptor 2 and downstream pathways of receptor tyrosine kinases involving phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin or mitogen-activated protein kinase in canine hemangiosarcoma cell lines.

Canine hemangiosarcoma (HSA) is a progressive malignant neoplasm with no current effective treatment. Previous studies showed that receptor tyrosine kinases and molecules within their downstream pathways involving phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (m-TOR) or mitogen-activated protein kinase (MAPK) were overexpressed in canine, human, and murine tumors, including HSA. The present study investigated the effects of inhibitors of these pathways in canine splenic and hepatic HSA cell lines using assays of cell viability and apoptosis. Inhibitors of the MAPK pathway did not affect canine HSA cell viability. However, cell viability was significantly reduced by exposure to inhibitors of vascular endothelial growth factor receptor 2 and the PI3K/Akt/m-TOR pathway; these inhibitors also induced apoptosis in these cell lines. These results suggest that these inhibitors reduce the proliferation of canine HSA cells by inducing apoptosis. Further study of these inhibitors, using xenograft mouse models of canine HSA, are warranted to explore their potential for clinical application.

L'hémangiosarcome canin (HS) est un néoplasme malin progressif sans traitement efficace actuel. Des études antérieures ont montré que les récepteurs à activité tyrosine kinase et les molécules dans la voie en aval impliquant la phospatidylinositol 3-kinase (PI3K)/Akt/cible mammalienne de rapamycine (m-TOR) ou la protéine kinase activée par mitogène (PKAM) étaient surexprimées dans les tumeurs canine, humaine, et murine, incluant HS. La présente étude visait à examiner les effets d'inhibiteurs de ces voies dans des lignées cellulaires spléniques et hépatiques de HS en utilisant des essais de viabilité cellulaire et d'apoptose. Les inhibiteurs de la voie PKAM n'ont pas affecté la viabilité de cellules d'HS canines. Toutefois, la viabilité cellulaire était réduite de manière significative suite à l'exposition à des inhibiteurs des récepteurs 2 du facteur de croissance de l'endothélium vasculaire et de la voie PI3K/Akt/m-TOR; ces inhibiteurs ont également induit l'apoptose dans ces lignées cellulaires. Ces résultats suggèrent que ces inhibiteurs réduisent la prolifération de cellules HS canines en induisant l'apoptose. Des études additionnelles de ces inhibiteurs, à l'aide de modèles murins de xénogreffes de HS canins, sont requises afin d'explorer leur potentiel pour une application clinique.(Traduit par Docteur Serge Messier).

Immunohistochemical detection of a potential molecular therapeutic target for canine hemangiosarcoma.

Canine hemangiosarcoma (HSA) is a progressive malignant neoplasm of dogs for which there is currently no effective treatment. A recent study suggested that receptor tyrosine kinases (RTKs), the PI3K/Akt/m-TOR and MAPK pathways are all activated in canine and human HSA. The aim of the present study was to investigate the overexpression of these proteins by immunohistochemistry in canine splenic HSA to identify potential molecular therapeutic targets. A total of 10 splenic HSAs and two normal splenic samples surgically resected from dogs were sectioned and stained with hematoxylin and eosin for histological diagnosis or analyzed using immunohistochemistry. The expression of RTKs, c-kit, VEGFR-2 and PDGFR-2, as well as PI3K/Akt/m-TOR and MEK was higher in canine splenic HSAs compared to normal spleens. These proteins may therefore be potential therapeutic targets in canine splenic HSA.

SiRNA knockdown of the DEK nuclear protein mRNA enhances apoptosis and chemosensitivity of canine transitional cell carcinoma cells.

Transitional cell carcinoma (TCC) in dogs is an aggressive malignant neoplasm, originating in the epithelium of the urinary bladder. The DEK nuclear protein is overexpressed in several types of human bladder cancer, where it is involved in chromatin reconstruction, gene transcription and apoptosis. Since DEK represents a potential therapeutic target for canine TCC, this study was designed to investigate DEK expression in canine TCC and to determine the effects of DEK mRNA silencing on TCC cells in vitro. The gene expression profiles of seven selected cancer-associated genes was assessed in four canine TCC cell lines and expression of DEK protein was evaluated in bladder tissue biopsies from healthy dogs and those affected with cystitis or TCC. After transfection of four canine TCC cell lines with DEK-specific or scrambled siRNA, annexin V staining was performed to evaluate apoptosis, and methylthiazole tetrazolium assays were performed to assess both cell viability and sensitivity to carboplatin. DEK mRNA expression was relatively high in canine TCC cells and expression of the DEK protein was significantly greater in TCC tumours compared with the other tissue samples. After transfection with DEK-specific siRNA, apoptosis, cell growth inhibition, and enhanced sensitivity to carboplatin were observed in all TCC cells assessed. These research findings suggest that DEK could be a potential therapeutic target for canine TCC.

Isolation and characterization of canine tumor endothelial cells.

The present study involved the isolation and characterization of canine tumor endothelial cells (TECs) from 2 malignancies. TECs were isolated using magnetic cell sorting following FITC labeling with UEA1 lectin, and they were characterized by measuring genetic and histopathological endothelial markers. Isolated TECs exhibited a cobblestone-like morphology and expressed both vascular endothelial growth factor receptor 2 (VEGFR2) and Von Willebrand factor (vWF). Further, both TECs and tumor cells derived from a seminoma exhibited increased C-X-C chemokine receptor type 7 (CXCR7) expression. However, CXCR7 expression was not detected in TECs and tumor cells derived from a hepatocellular carcinoma. Understanding TEC specific traits may be important in the development of more efficacious anti-angiogenic therapies that do not induce adverse effects.

Inhibition of survivin influences the biological activities of canine histiocytic sarcoma cell lines.

Canine histiocytic sarcoma (CHS) is an aggressive malignant neoplasm that originates from histiocytic lineage cells, including dendritic cells and macrophages, and is characterized by progressive local infiltration and a very high metastatic potential. Survivin is as an apoptotic inhibitory factor that has major functions in cell proliferation, including inhibition of apoptosis and regulation of cell division, and is expressed in most types of human and canine malignant neoplasms, including melanoma and osteosarcoma. To investigate whether survivin was expressed at high levels in CHS and whether its expression was correlated with the aggressive biological behavior of CHS, we assessed relation between survivin expression and CHS progression, as well as the effects of survivin inhibition on the biological activities of CHS cells. We comparatively analyzed the expression of 6 selected anti-apoptotic genes, including survivin, in specimens from 30 dogs with histiocytic sarcoma and performed annexin V staining to evaluate apoptosis, methylthiazole tetrazolium assays to assess cell viability and chemosensitivity, and latex bead assays to measure changes in phagocytic activities in 4 CHS cell lines and normal canine fibroblasts transfected with survivin siRNA. Survivin gene expression levels in 30 specimens were significantly higher than those of the other 6 genes. After transfection with survivin siRNA, apoptosis, cell growth inhibition, enhanced chemosensitivity, and weakened phagocytic activities were observed in all CHS cell lines. In contrast, normal canine fibroblasts were not significantly affected by survivin knockdown. These results suggested that survivin expression may mediate the aggressive biological activities of CHS and that survivin may be an effective therapeutic target for the treatment of CHS.