Deuterium Magnetic Resonance Imaging Using Deuterated Water-Induced 2H-Tissue Labeling Allows Monitoring Cancer Treatment at Clinical Field Strength.

PURPOSE: An accurate and noninvasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice. EXPERIMENTAL DESIGN: MIA PaCa-2 pancreatic carcinoma and C26 colorectal carcinoma models of BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days of free drinking of 30% D2O to track 2H distribution in tissues. 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration was also measured in MIA PaCa-2-bearing mice. Confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS, and histopathology were performed. RESULTS: The mouse's whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI, and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments. CONCLUSIONS: Deuterium MRI at 1.5T proved feasible to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for preliminary assessment of radiotherapy and chemotherapy of cancer.

Efficacy and adverse events of anthracycline and propranolol combination in five dogs with stage 3 hemangiosarcoma.

Background: Canine hemangiosarcoma (HSA), which originates from endothelial cells, is one of the most common malignant neoplasms that frequently develop metastatic lesions. Although anthracycline-based HSA treatment strategies have been widely investigated, reliable therapy for dogs with clinically advanced-stage HSA (stage 3 HSA) has not been established yet. Recently, several studies have demonstrated that propranolol, a beta-adrenergic receptor antagonist, exhibits anti-tumor effects against tumors originating from vascular endothelial cells, indicating the possibility that propranolol is a candidate adjunctive agent for anthracycline-based therapy in dogs with stage 3 HSA. This study aimed to evaluate the clinical efficacy and adverse events (AEs) of anthracycline and propranolol combination in stage 3 HSA-affected dogs. Case Description: We retrospectively investigated five dogs diagnosed with stage 3 HSA which were administered with both anthracycline and propranolol during the same period between January 2020 and August 2021. Clinical benefit was observed in four of five HSA dogs (one of complete response, one of partial response, and two of stable disease) with gross metastatic lesions by anthracycline and propranolol combination. Notably, some or all of the metastatic lesions were reduced in two cases. In all five dogs administered with anthracycline and propranolol combination, no serious and irreversible AEs were observed. Conclusion: Our findings demonstrate the efficacy and safety of anthracycline and propranolol combination in stage 3 HSA-affected dogs. Further studies are needed to establish treatment protocols based on anthracycline and propranolol combination for dogs with advanced HSA.

Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors.

Malignant melanoma (MM) is one of the most common tumors in both dogs and humans. As canine MM (CMM) and human MM (HMM) have similar clinical characteristics, CMM appears to be a good clinical model for HMM. We previously demonstrated that the introduction of a synthetic double-strand-microRNA-634 (miR-634) mimic triggered apoptotic cell death by directly targeting the genes associated with cytoprotective processes in various human cancer cell lines, including those of HMM. This study aimed to investigate the antitumor effects of the local administration of miR-634 on spontaneous CMMs to provide a basis for future applications of miR-634 formulations in HMM treatment. We found that miR-634 administration induced apoptosis in CMM cell lines in vitro via downregulation of Asct2, Nrf2, and survivin expression, similar to the mechanisms in HMM cell lines. Furthermore, intratumoral miR-634 administration induced antitumor effects in four of seven spontaneous CMM cases, with no adverse effects. Local administration of miR-634 to lung metastasis under ultrasound guidance induced tumor shrinkage. These results confirm the antitumor effect of the local administration of miR-634 in spontaneous CMM, a model for spontaneous HMM, thereby providing a novel treatment strategy for HMM.

The effects of BPA-BNCT on normal bone: determination of the CBE value in mice‡.

Boron neutron capture therapy (BNCT) with p-boronophenylalanine (BPA) is expected to have less effect on the decrease in normal bone strength than X-ray therapy. However, the compound biological effectiveness (CBE) value necessary to convert the boron neutron capture reaction (BNCR) dose into a bioequivalent X-ray dose has not been determined yet. The purpose of this study was to evaluate the influence of BNCT on normal bone in mice and to elucidate the CBE factor. We first searched the distribution of BPA in the normal bone of C3H/He mice and then measured the changes in bone strength after irradiation. The CBE value was determined when the decrease in bone strength was set as an index of the BNCT effect. The 10B concentrations in the tibia after subcutaneous injection of 125, 250 and 500 mg/kg BPA were measured by prompt gamma-ray spectroscopy and inductively coupled plasma (ICP)-atomic emission spectrometry. The 10B mapping in the tibia was examined by alpha-track autoradiography and laser ablation-ICP-mass spectrometry. The 10B concentration increased dose-dependently; moreover, the concentrations were maintained until 120 min after BPA administration. The administered 10B in the tibia was abundantly accumulated in the growth cartilage, trabecular bone and bone marrow. The bone strength was analyzed by a three-point bending test 12 weeks after irradiation. The bending strength of the tibia decreased dose-dependently after the irradiation of X-ray, neutron and BNCR. The CBE factor was obtained as 2.27 by comparing these dose-effect curves; the value determined in this study will enable an accurate dosimetry of normal bone.

Successful rescue treatment using chlorambucil for presumed recurrence of sinonasal lymphoma in a cat.

Case summary: A 12-year-old male neutered domestic shorthair cat presented with a 2-week history of serous unilateral nasal discharge, swelling of the nasal bridge and sneezing. Whole-body CT revealed a mass filling the entire right nasal cavity with lysis of the cribriform plate. The cat was diagnosed with sinonasal large-cell lymphoma based on cytopathological analysis, with PCR-based lymphocyte clonality testing showing a monoclonal population with rearrangement of the immunoglobulin heavy chain gene. The cat received radiotherapy with a dose of 30 Gy in seven fractions given three times weekly, and then cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)-based chemotherapy was initiated soon after completion of the radiotherapy schedule. Despite this treatment, CT performed 4 months after radiotherapy revealed enlargement of the lesion in the right nasal cavity consistent with presumed progression of the cat's lymphoma. The cat then received rescue chemotherapy with chlorambucil, which markedly reduced the size of the disease burden in the nasal and frontal sinus without severe adverse effects. At the time of writing, the cat was receiving chlorambucil for 7 months without any clinical signs suggestive of tumour relapse. Relevance and novel information: To our knowledge, this is the first case of feline sinonasal lymphoma with chlorambucil used as rescue chemotherapy. This case indicates that chemotherapy with chlorambucil may be a useful treatment option for cats with relapsing sinonasal lymphoma following radiotherapy and/or CHOP-based chemotherapy.

Computed tomography-based evaluation for normal adrenal gland size independent of body weight in dogs.

Background: Computed tomography (CT) is useful for evaluating the anatomical position of the adrenal gland and the presence of adrenal tumor (AT) metastasis or vascular invasion from ATs. Aim: To determine a weight-independent reference for adrenal gland size in normal dogs using CT. Methods: The medical records database of Gifu University was searched for data collected from April 2010 to December 2015 for records of dogs that underwent abdominal CT. The CT images were retrospectively analyzed using a Digital Imaging and Communications in Medicine viewer. The ratios of the minor axes of the adrenal glands to the height of the spinal cavity were investigated. Results: In total, 939 dogs were included. The left and right adrenal minor axes showed a moderate positive correlation with body weight (right: r = 0.61, p < 0.05; left: r = 0.54, p < 0.05). The L4 spinal cavity height showed a strong positive correlation with body weight (r = 0.82, p < 0.05). The left and right adrenal minor axis/L4 spinal cavity ratio did not correlate with body weight (right: r = 0.02, p = 0.53; left: r = -0.082, p < 0.05). The 95% confidence intervals of the adrenal minor axis/L4 spinal cavity ratios were as follows: right: 0.5-1.3 and left: 0.5-1.4. Conclusion: These results indicate that the adrenal minor axis/L4 spinal cavity ratio can be used as an index of adrenal gland size that is not affected by body weight. Patients in whom the adrenal minor axis/L4 spinal cavity ratio exceeds the upper limit (right 1.3, left 1.4) may have adrenal swelling.

Analysis of Aß-induced neurotoxicity and microglial responses in simple two- and three-dimensional human iPSC-derived cortical culture systems.

The extracellular accumulation of amyloid-ß (Aß) in plaques and associated neurodegeneration are the pathological hallmarks of Alzheimer's disease (AD). These plaques are surrounded by microglia-the resident tissue macrophages of the brain parenchyma that originate from primitive macrophages from the embryonic yolk sac. Microglia, including a unique subpopulation called "disease-associated microglia" (DAM), are strongly implicated in AD pathology; however, their exact function and physiology remain largely unknown. Notably, simple cell and tissue culture systems that adequately recreate the brain microenvironment and can simulate critical aspects of AD pathology could fundamentally contribute to elucidating microglial function in disease development and progression. Thus, we added human-induced pluripotent stem cell (hiPSC)-induced primitive macrophages (hiMacs) to hiPSC-induced cortical neurons (cell model) and cortical organoids (tissue model). The treatment of these culture systems with the O-acyl isopeptide of Aß1-42, which reverts to natural extracellular Aß1-42 at neutral pH and starts self-aggregation, caused the degeneration of hiPSC-induced cortical neurons in 2D culture and within cortical organoid cultures. Notably, the hiMacs phagocytosed extracellular Aß and exhibited a DAM-like phenotype. In both cell and tissue organoid culture systems, neurodegeneration was attenuated by the addition of hiMacs. Moreover, in cortical organoids, Aß plaques formed more circular and fewer hotspot-like morphological structures in the vicinity of hiMacs. These findings demonstrate the utility of simple hiPSC-induced cortical cell and tissue culture systems supplemented with hiMacs for elucidating critical aspects of AD pathology, such as microglial function and physiology. Adopting such systems in routine research practice may lead to the development of novel therapeutic strategies for AD.

Combined Hypofractionated Radiotherapy and Chemotherapy Versus Hypofractionated Radiotherapy Alone for Cats with Localized Sinonasal Lymphoma.

Despite considering hypofractionated radiotherapy (HRT) a useful treatment option for feline localized sinonasal lymphoma (stage I), the benefits of additional chemotherapy remain controversial. This retrospective cohort study evaluated the efficacy of the early initiation of chemotherapy in combination with HRT (HRTC) to prolong the progression-free survival (PFS) and overall survival (OS) in cats with localized sinonasal lymphoma compared with HRT alone. While 24 eligible cats received HRT alone (HRT group), 18 received HRTC (HRTC group). The total median administered dose was 35 Gy, with one fraction per week, for a median of five fractions. In the HRTC group, the chemotherapy protocol was cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based and cyclophosphamide, vincristine, and prednisolone (COP)-based in 14 (78%) and 4 cats (22%), respectively. Cats in the HRTC group had significantly longer PFS (677 versus 104 days; P = .04) and OS (983 versus 263 days; P = .04) than those in the HRT group. Considering the poor outcome in the HRT group despite the cats having received rescue chemotherapy for progressive disease, the early initiation of additional chemotherapy along with HRT may be recommended for feline localized sinonasal lymphoma.

Outcome of Localized Bile Duct Carcinoma in Six Dogs Treated with Liver Lobectomy.

The prognosis for bile duct carcinoma in dogs is generally believed to be poor. However, only a few studies have evaluated the postoperative outcomes in such cases. The objective of this case series was to describe the postoperative outcomes of localized intrahepatic bile duct carcinoma in dogs. The electronic medical records of 16 dogs with bile duct carcinoma were reviewed, and 6 dogs were included in the study. All cases were diagnosed as bile duct carcinoma using postoperative pathology, and five of them had already been diagnosed using preoperative core biopsy. The tumors in all of the dogs were confirmed as completely resected on histopathological examination. Two dogs received toceranib following the surgery. The median follow-up time was 693 days (range, 420-1386 days), with a median survival time of 894 days (range, 420-1386 days). Local recurrence or distant metastases were detected in two of the six dogs (33%) on 354 and 398 days following surgery, respectively. The median progression-free survival was 492 days (range, 354-1386 days). In conclusion, dogs with localized intrahepatic bile duct carcinoma had a good prognosis following complete surgical resection.

A frameshift variant in the EXT1 gene in a feline leukemia virus-negative cat with osteochondromatosis.

Osteochondromatosis is a benign proliferative disorder characterized by cartilage-capped bony protuberances. In humans and most mammals, variants in the EXT1 or EXT2 gene are strongly correlated with the etiology of osteochondromatosis. However, in cats, osteochondromatosis has only been associated with feline leukemia virus infection. In this study, to explore other factors involved in the etiology of feline osteochondromatosis, we examined the EXT1 and EXT2 genes in a feline leukemia virus-negative cat with osteochondromatosis. Genetic analysis revealed a heterozygous single base pair duplication in exon 6 of the EXT1 gene (XM_023248762.2:c.1468dupC), leading to a premature stop codon in the EXT1 protein. Notably, this frameshift variant is recognized as one of the most common pathogenic variants in human osteochondromatosis. Our data suggest for the first time that genetic variants can have etiologic roles in osteochondromatosis in cats, as in humans and other animals.

Radiological Arterial Anatomy in Mature Microminipigs as a Pre-clinical Research Model in Interventional Radiology.

PURPOSE: To define the radiological arterial anatomy in mature microminipigs as a pre-clinical research animal model in interventional radiology. MATERIALS AND METHODS: Five female microminipigs (weighing 20.9 ± 2.9 kg) were used in this study. Under general anesthesia, computed tomography (CT) angiography was performed using a 16-slice CT scanner. CT was performed 12 s after initiation of an intravenous injection of 40 ml of nonionic contrast media at 3.0 ml/second using a power injector. The transverse CT angiography images were evaluated using a digital imaging and communication in medicine viewer, and the diameters of the following 41 arteries were measured.: ascending aorta, descending aorta, thoracoabdominal aorta, abdominal aorta, pulmonary artery trunk, both pulmonary, brachiocephalic artery, short common bicarotid, both common carotid artery, subclavian, bronchial, internal mammary, celiac, common hepatic, left lateral hepatic, middle hepatic, left hepatic, gastroduodenal, cranial duodenopancreatic, splenic, left gastric, cranial mesenteric, ileocolic , bilateral colic artery, caudal mesenteric, cranial rectal, renal, both external iliac arteries, internal iliac common trunk, and both internal iliac and femoral arteries. RESULTS: The microminipigs' vascular anatomy was the same as domestic pig anatomy and similar to human anatomy. The diameter of the aorta (ascending to abdominal) was 17.1-7.0 mm, iliac and femoral arteries (internal iliac common trunk to femoral artery): 5.5-3.8 mm, pulmonary arteries: 9.3-14.7 mm, and major first aortic branches (e.g., celiac or brachiocephalic artery): 2.2-9.2 mm. CONCLUSION: This study defined the microminipig arterial anatomy in the trunk.

Feasibility study for inducing the skeletal muscle fibrosis via irradiation using two mouse strains.

PURPOSE: Although the mechanism of onset and progression of radiation-induced fibrosis (RIF) has been studied, most studies to date have focused on pulmonary fibrosis. There are few studies on murine RIF in the skeletal muscle, and the pathogenic mechanism remains unclear. This pilot study aimed to evaluate the feasibility to create a murine model of RIF in the skeletal muscle and analyze strain differences in fibrosis sensitivity. MATERIALS AND METHODS: Two mouse strains, C57BL/6 and C3H/He, were used. Their right hind limbs were irradiated at a dose of 25 Gy once a week for three fractions. Gastrocnemius muscles were collected at day 4, and weeks 2, 4, 8, 12, and 24 after the third irradiation and subjected to histopathological examination and immunoblotting. RESULTS: In C57BL/6 mice, chronic inflammation and an increased expression of transforming growth factor-ß (TGF-ß) and fibronectin were observed 2 weeks after irradiation. A significant increase in fibrosis was detected after 8 weeks. However, in C3H/He mice, the expression of TGF-ß and fibronectin increased 8 weeks after irradiation, and fibrosis significantly increased after 12 weeks. Moreover, the degrees of inflammation and fibrosis were more remarkable in C57BL/6 mice than in C3H/He mice. CONCLUSION: The onset and degree of fibrosis may be associated with the expression of TGF-ß and fibronectin, and inflammation, in a strain-specific manner. Therefore, a murine model of RIF in the skeletal muscle could be created using the indicated method, suggesting that the C57BL/6 strain is more sensitive to fibrosis in the skeletal muscle, as well as the lung, than the C3H/He strain. Radiation-induced fibrosis in the skeletal muscle could be detected in C57BL/6 and C3H/He mice, with C57BL/6 mice being more sensitive to fibrosis in the skeletal muscle than C3H/He mice.

Spatiotemporal imaging of redox status using in vivo dynamic nuclear polarization magnetic resonance imaging system for early monitoring of response to radiation treatment of tumor.

In general, the effectiveness of radiation treatment is evaluated through the observation of morphological changes with computed tomography (CT) or magnetic resonance imaging (MRI) images after treatment. However, the evaluation of the treatment effects can be very time consuming, and thus can delay the verification of patient cases where treatment has not been fully effective. It is known that the treatment efficacy depends on redox modulation in tumor tissues, which is an indirect effect of oxidizing redox molecules such as hydroxyl radicals and of reactive oxygen species generated by radiation treatment. In vivo dynamic nuclear polarization-MRI (DNP-MRI) using carbamoyl-PROXYL (CmP) as a redox sensitive DNP probe enables the accurate monitoring of the anatomical distribution of free radicals based on interactions of electrons and nuclear spin, known as Overhauser effect. However, spatiotemporal response of the redox status in tumor tissues post-irradiation remains unknown. In this study, we demonstrate the usefulness of spatiotemporal redox status as an early imaging biomarker of tumor response after irradiation using in vivo DNP-MRI. Our results highlight that in vivo DNP-MRI/CmP allowed us to visualize the tumor redox status responses significantly faster and earlier compared to the verification of morphological changes observed with 1.5 T MRI and cancer metabolism (Warburg effect) obtained by hyperpolarized 13C pyruvate MRS. Our findings suggest that the early assessment of redox status alterations with in vivo DNP-MRI/CmP probe may provide very efficient information regarding the effectiveness of the subsequent radiation treatment.

Functional rice with tandemly repeated Cbl-b ubiquitin ligase inhibitory pentapeptide prevents denervation-induced muscle atrophy in vivo.

Ubiquitin ligase Casitas B-lineage lymphoma-b (Cbl-b) play a critical role in nonloading-mediated skeletal muscle atrophy: Cbl-b ubiquitinates insulin receptor substrate-1 (IRS-1), leading to its degradation and a resulting loss in muscle mass. We reported that intramuscular injection of a pentapeptide, DGpYMP, which acts as a mimic of the phosphorylation site in IRS-1, significantly inhibited denervation-induced skeletal muscle loss. In order to explore the possibility of the prevention of muscle atrophy by diet therapy, we examined the effects of oral administration of transgenic rice containing Cblin (Cbl-b inhibitor) peptide (DGYMP) on denervation-induced muscle mass loss in frogs. We generated transgenic rice seeds in which 15 repeats of Cblin peptides with a WQ spacer were inserted into the rice storage protein glutelin. A diet of the transgenic rice seeds had significant inhibitory effects on denervation-induced atrophy of the leg skeletal muscles in frogs, compared with those receiving a diet of wild-type rice.

A retrospective analysis on the outcome of 18 dogs with malignant ovarian tumours.

Little evidence is available regarding the prognosis of dogs with malignant ovarian tumours. The objective of this retrospective study was to describe the outcomes and determine the prognostic factors for dogs with malignant ovarian tumours following treatment, including surgery with or without adjuvant therapy. Eighteen dogs were studied, their median age was 12 years (range: 7-15 years), and their median body weight was 6.9 kg (range: 2.3-17.8 kg). Following histopathologic diagnoses revealed that granulosa cell tumour was the most common type (n = 9), followed by dysgerminoma (n = 5), and adenocarcinoma (n = 4). Eleven dogs had surgery alone. Seven dogs had surgery with adjuvant therapy, including chemotherapy and/or radiotherapy. The median survival time (ST) was 1009 days when only deaths owing to the ovarian tumours were considered, and predictors of median ST were T-category (≥ T3, 443 days vs ≤ T2, 1474 days; P = .002), presence of metastatic disease (present, 391 days vs absent, 1474 days; P < .001) and lymphovascular space invasion (present, 428 days vs absent, 1474 days; P = .003) in a univariate analysis. Median ST in dogs with granulosa cell tumour seemed longer than in dogs with dysgerminoma and adenocarcinoma, although the difference was statistically insignificant (1474 days vs 458 days, respectively; P = .10). Considering the good prognosis, aggressive treatment can be recommended for dogs with malignant ovarian tumours, especially early-stage cases. Despite metastasis being present at diagnosis, half of the dogs with metastasis survived for more than 1 year.

Dynamic contrast-enhanced computed tomography lymphangiography with intranodal injection of water-soluble iodine contrast media in microminipig: imaging protocol and feasibility.

OBJECTIVES: To evaluate the optimal imaging protocol and the feasibility of intranodal dynamic contrast-enhanced computed tomography lymphangiography (DCCTL) in microminipigs. METHODS: The Committee for Animal Research and Welfare provided university approval. Five female microminipigs underwent DCCTL after inguinal lymph node injection of 0.1 mL/kg of iodine contrast media at a rate of 0.3 mL/min with three different iodine concentrations: group 1, 75 mgI/mL; group 2, 150 mgI/mL; and group 3, 300 mgI/mL. The CT values of the venous angle, thoracic duct (TD), cisterna chyli, iliac lymphatic duct, and iliac lymph node were measured; increases in CT values pre- to post-contrast were assessed as the contrast-enhanced index (CEI). Multi-detector row CT (MDCT) and volume rendering images showing the highest CEI were qualitatively evaluated. RESULTS: The CEI of all lymphatics peaked at 5-10 min. The mean CEI of TD at 10 min of group 2 (193.0 HU) and group 3 (201.5 HU) were significantly higher than that of group 1 (70.7 HU) (p = 0.024). The continuity and overall diagnostic acceptability of all lymphatic system components were better in group 3 (3.6 and 3.0, respectively) than group 1 (2.6 and 1.6) and group 2 (3.0 and 2.6) (p = 0.249 and 0.204). CONCLUSIONS: The optimal imaging protocol for intranodal DCCTL could be dual-phase imaging at 5 and 10 min after the injection of 300 mgI/mL iodinated contrast media. DCCTL provided good images of lymphatics and is potentially feasible in clinical settings. KEY POINTS: • Dynamic contrast-enhanced computed tomography lymphangiography with intranodal injection of water-soluble iodine contrast media showed the highest enhancement of all lymphatics at scan delays of 5 and 10 min. • The optimal iodine concentration for intranodal dynamic contrast-enhanced computed tomography lymphangiography might be 300 mgI/mL. • Intranodal dynamic contrast-enhanced computed tomography lymphangiography provided good images of all the lymphatic system components and is potentially feasible in clinical settings.

Nuclear Accumulation of ß-Catenin in Cancer Stem Cell Radioresistance and Stemness in Human Colon Cancer.

BACKGROUND/AIM: The aim of this study was to examine whether the Wnt/ß-catenin signal activation is a cause of radioresistance in colon cancer by assessing the ß-catenin localization and its correlation with cancer stem cells (CSCs). MATERIALS AND METHODS: The nuclear levels of ß-catenin, the hallmark of Wnt activation, were analyzed in HCT116 and SW480 cells by immunohistochemistry, before and after irradiation. Further, we assessed CSC populations by staining for aldehyde dehydrogenase-1 (ALDH1) and CD44. RESULTS: ß-catenin was localized predominantly in the nucleus and plasma membrane in SW480 and HCT116 cells, respectively. Compared to HCT116 cells, SW480 cells displayed higher Wnt activation. At 24 h after irradiation, most of the DSBs in SW480 cells were repaired, but were still present in HCT116 cells. Additionally, compared to HCT116 cells, a significantly higher proportion of SW480 cells were ALDH1- and CD44-positive. CONCLUSION: Colon cancers with nuclear ß-catenin accumulation demonstrated greater radio-resistance with a higher number of CSCs.

Hypofractionated radiotherapy in nine dogs with unresectable solitary lung adenocarcinoma.

Although lung lobectomy is the most common treatment option for dogs with solitary lung tumors, surgery often cannot be performed at the time of diagnosis. In this retrospective, case series study, we described the effects of hypofractionated radiotherapy for tumor mass reduction in nine dogs with solitary lung adenocarcinoma that were later considered for surgical resection, and we assessed the tolerability of the radiation protocol. Tumors were deemed unresectable by the attending veterinarian. The dose prescription was 7.0-12.0 Gy/fraction in four to seven fractions, administered weekly for a total dose of 40-50 Gy. Treatment planning prioritized normal tissue dose constraints. The median interval between the last radiotherapy session and maximum tumor size reduction was 56 (range: 26-196) days, with six and three dogs exhibiting a partial response and stable disease, respectively. Although acute and late radiation-induced toxicity to the skin and/or lungs developed in all nine dogs, it was self-limiting or improved with short-term anti-inflammatory treatment. Tumor progression after initial size reduction was confirmed in three dogs at 62, 126, and 175 days, respectively, after the last radiotherapy session. Seven of the nine dogs underwent lobectomy a median of 68 days after radiotherapy when tumors were in partial response or stable disease or at the time of progression, and five received systemic chemotherapy concurrent with or after radiotherapy. These findings suggest that hypofractionated radiotherapy for canine solitary lung adenocarcinoma is useful when the tumor is large or when surgery cannot be performed immediately after diagnosis.

Survival analysis in dogs with urinary transitional cell carcinoma that underwent whole-body computed tomography at diagnosis.

This retrospective study aimed to evaluate factors associated with survival and to compare characteristics between tumour localizations in dogs with urinary transitional cell carcinoma (TCC) that underwent whole-body computed tomography (CT) at diagnosis. Dogs with histologically confirmed TCC that received medical therapy between 2010 and 2017 were included; dogs that underwent surgery or radiotherapy for the primary tumour were excluded. According to the CT findings, primary tumour localization (classified into the Bladder, Urethra and Bladder and Urethra groups), prostate involvement, iliosacral lymphadenomegaly, sternal lymphadenomegaly and metastasis to the bone and lung were evaluated for survival analysis. CT at diagnosis revealed iliosacral lymphadenomegaly, sternal lymphadenomegaly, bone metastasis and lung metastasis in 47.7%, 18.5%, 24.6% and 35.4% of the 65 included dogs, respectively. The overall median survival time was 196 days. On multivariable analysis, TCC localization (hazard ratio [HR], 1.90; P = .037), bone metastasis (HR, 2.76; P = .013) and sternal lymphadenomegaly (HR, 3.56; P = .004) were significantly associated with survival. Compared to the Bladder group (n = 16), the Urethra group (n = 26) had higher metastasis rates to the bone (6.3% vs 42.3%; P = .045) and lung (6.3% vs 46.2%; P = .022). The survival time was shorter in the Urethra group than in the Bladder group (121.5 vs 420 days; P < .001), and it was similar only in female dogs (247 vs 420 days; P = .031). These findings suggest that whole-body CT could be valuable for predicting the prognosis in urinary TCC.

Endoscopic Ultrasound-Guided Fine-Needle Injection of Hydrogen Peroxide into the Pancreas: Feasibility and Tolerability Study Using a Survival Porcine Model.

Hydrogen peroxide (H2O2) has been reported to be an effective radiation sensitizer for various cancers. A combination therapy comprising fine-needle injection (FNI) of H2O2 under endoscopic ultrasound (EUS) guidance and chemoradiation might improve treatment outcomes of pancreatic cancer; however, there have been no reports thus far. The aims of this study were to evaluate the feasibility and safety of EUS-FNI of H2O2 into the pancreas using a porcine survival model. EUS-FNI was performed in the pancreas of six pigs, which were randomly divided into three groups based on the solution injected: group 1, 2 mL of sodium hyaluronate (control); group 2, 0.5 mL of H2O2; group 3, 2 mL of H2O2. To evaluate any adverse events, blood tests and computed tomography (CT) were performed before and after FNI, as well as days 3 and 7 subsequently. The pigs were necropsied on day 7. Histologic evaluation was performed according to the criteria for experimental acute pancreatitis. EUS-FNI was successful in all pigs. CT immediately after FNI revealed gas formation in the FNI area in groups 2 and 3. No adverse events were revealed by blood tests and CT. Histologic evaluations revealed pancreatitis scores of 5 and 5 in group 1, 7 and 7 in group 2 and 14 and 15 in group 3. EUS-FNI of H2O2 into the pancreas is feasible; however, it could cause pancreatitis. FNI of H2O2 into only the pancreatic tumor might be ideal in minimizing possible adverse events.