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1.
二乙基亚硝胺诱发大鼠肝癌模型的建立及其应用   总被引:10,自引:0,他引:10  
用二乙基亚硝胺诱发大鼠肝癌模型,通过病理学与影像学进行对照检查,证实成功诱发出肝癌病灶模型,并具有人相象的病变过程及病理学变化特征,同时具有人肝癌相似的影像学表现,是一种研究人类肝癌的理想动物模型。  相似文献   

2.
CASE HISTORY: A 14-year-old neutered male Bearded Collie was presented with a history of recurrent, intermittent urinary incontinence of 7 years duration.

CLINICAL FINDINGS: A large, firm, non-painful mass was found in the mid-abdominal region on palpation. Ultrasonography of the mass revealed a compartmentalised structure with mixed echogenicity, and which did not appear to be associated with any of the abdominal organs. Ultrasound-guided fine needle aspirates contained several clusters of epithelial cells with cytological features of hepatocytes. At exploratory laparotomy, the mass was found in the gastrosplenic ligament within the greater omentum.

PATHOLOGICAL FINDINGS AND DIAGNOSIS: Histopathologically, the mass consisted of sheets of hepatocytes, but without the characteristic hepatic architecture. The cells showed moderate variation in nuclear size and were sometimes binucle- ate. A diagnosis of hepatocellular carcinoma (HCC) in the mesentery was made.

CLINICAL RELEVANCE: The presence of ectopic hepatic tissue has been reported rarely in man and cats, but not in the dog. Neoplastic transformation of ectopic hepatic tissue is seen in man. This is the first report of the presentation, clinical findings and treatment of a dog with ectopic HCC.  相似文献   

3.
In this comparative review, histomorphological features of common nonneoplastic and neoplastic hepatocyte lesions of rats and humans are examined using H&E-stained slides. The morphological similarities and differences of both neoplastic (hepatocellular carcinoma and hepatocellular adenoma) and presumptive preneoplastic lesions (large and small cell change in humans and foci of cellular alteration in rats) are presented and discussed. There are major similarities in the diagnostic features, growth patterns and behavior of both rat and human hepatocellular proliferative lesions and in the process of hepatocarcinogenesis. Further study of presumptive preneoplastic lesions in humans and rats should help to further define their role in progression to hepatocellular neoplasia in both species.  相似文献   

4.
In this study, plasma time-activity curves of 99mTc-mebrofenin were used to quantify hepatic function in dogs before and after induction of hepatic damage using a hepatotoxic agent. Nine dogs were determined to be healthy on the basis of physical examination, laboratory data and hepatic imaging. Plasma samples were collected 1, 3, 5, 7, 9, 15, 20, 30, 40, 50, and 60 minutes following a peripheral venous injection of 111-222 MBq (3-6 mCi) of 99mTc-mebrofenin. The area under the plasma time-activity curve (AUC) was calculated using two different methods and compared to direct measurement of the hepatic extraction efficiency. First pass hepatic extraction efficiency of 99mTc-mebrofenin was calculated from differential equation analysis of a two-compartment model following mesenteric venous injection of the radiopharmaceutical. In 7 of the original 9 dogs and 2 additional healthy dogs, plasma clearance and hepatic extraction efficiency determination were repeated following induction of hepatic injury by thiacetarsamide (3 mg/kg IV twice daily for 1 day). In one additional dog, hepatic injury was induced using carbon tetrachloride (0.3 ml/kg IP). Plasma time-activity curves of 99mTc-mebrofenin had kinetics of a two compartment model. Area under the curve was highly correlated with hepatic extraction efficiency. The AUC integrated from 1-60 minutes (AUC60) had the best correlation with hepatic extraction efficiency (r2 = 0.978, p < 0.001). A formula for calculation of hepatic extraction efficiency was derived using linear regression analysis: hepatic extraction efficiency = 105.583 - 3.099 x 10(5) x AUC60. Plasma clearance of a peripheral venous injection of 99mTc-mebrofenin is a simple, non-invasive, convenient method to quantify hepatic function which can be performed without a gamma camera.  相似文献   

5.
Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE) are standard treatments for advanced hepatocellular carcinoma (HCC) and particularly for unresectable tumors or liver metastases in humans. However, reports on TACE used in veterinary medicine are few. This study aimed to evaluate the feasibility and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE). We performed DEB-TACE in four clinically normal dogs and pharmacokinetically compared the results against hepatic arterial infusion (HAI) of cisplatin in two dogs. Drug-eluting beads (DEB) loaded with cisplatin were injected through a microcatheter for selective embolization of the left hepatic artery. After embolization, computed tomography (CT) images and histological examination findings were obtained during a 4-week observation period. Serum platinum concentrations were measured to evaluate cisplatin after each procedure. Biochemical analysis was performed during a 12-week observation period. Embolization was successful in all dogs, and there were no clinically apparent abnormalities. Embolization was confirmed up to 4 weeks after DEB-TACE in two of the four dogs and up to 1 week in the other two dogs using postoperative CT images. Cisplatin was not detected in peripheral veins in all dogs after DEB-TACE, but it was detected in trace amounts after HAI. DEB-TACE using cisplatin was safe and well tolerated by normal dogs. DEB-TACE may be useful in terms of determining systemic toxicity and drug concentration within tumors.  相似文献   

6.
Abstract: A 12‐year‐old, neutered male, mixed‐breed dog was presented to The Ohio State University Veterinary Teaching Hospital with a history of weight loss and weakness. Laboratory abnormalities reported by the referring veterinarian during the past year included increased alkaline phosphatase (ALP) activity, hyperalbuminemia, and nonregenerative anemia. On referral, the dog appeared hydrated and had moderate muscle wasting and hepatomegaly. A large lobular hepatic mass was observed ultrasonographically. Laboratory results included mild to moderate nonregenerative anemia, urine‐specific gravity of 1.035, 3+ proteinuria, increased serum activities of alanine aminotransferase (229 U/L, reference interval 10–55 U/L), ALP (813 U/L, reference interval 15–120 U/L), and the steroid‐induced isoform of ALP (676 U/L, reference interval 0–6 U/L), marked hyperalbuminemia (5.3 g/dL, reference interval 2.9–4.2 g/dL), and an increased A/G ratio (1.7). Hyperalbuminemia was confirmed by reanalysis on 2 different analyzers and by agarose gel electrophoresis, and colloid osmotic pressure (COP) was markedly increased (42.5 mmHg, reference interval 20–25 mmHg). Cytologic examination of a fine‐needle aspirate of the hepatic mass indicated hepatocellular proliferation; histologic examination of an excisional biopsy confirmed hepatocellular carcinoma. Three weeks after surgery, the albumin concentration, A/G ratio, COP, and ALT activity had normalized, but ALP activities remained high. We hypothesized that hyperalbuminemia developed secondary to hepatocellular carcinoma due to increased synthesis of albumin by malignant hepatocytes or due to decreased negative feedback from impaired hepatocellular osmoreceptivity. Hepatocellular carcinoma has been associated with paraneoplastic secretion of other proteins, but hyperalbuminemia has been reported only once in a human patient and has not previously in dogs.  相似文献   

7.

Background

The most common haemostatic abnormality in dogs with cancer is hypercoagulability. A transient hypercoagulability has been documented in people with hepatocellular carcinoma (HCC) that resolves within weeks following hepatic tumour resection.

Objective

The objective was to compare the haemostatic status of dogs with liver tumours and healthy control dogs, by comparing coagulation and thromboelastography (TEG) measurements at three time points.

Methods

Liver tumour and healthy control dogs receiving surgery for liver lobectomy and ovariohysterectomy, respectively, were prospectively enrolled. All dogs had blood collected at three time points: pre-operative, 24 h post-operative and ~2 weeks post-operative. Haematological and haemostatic values were compared across time points in each group using repeated measures ANOVA tests.

Results

Ten and eight dogs were enrolled for the liver and control groups, respectively. Platelet count was significantly higher in the liver group than the control group at all time points, but within the normal range (pre-operative: 438.7 vs. 300.9 × 109/L, p = .0078; 24 h post-operative: 416.2 vs. 283.9 × 109/L, p = .0123; 10–14 days post-operative: 524.6 vs. 317.3 × 109/L, p = .0072). The measure of the overall coagulant state (G-value) was significantly increased for the liver group compared to the control group at all time points (pre-operative: 15.6 vs. 8.6 d/sc, p = .0003; 24 h post-operative: 18.3 vs. 11.2 d/sc, p = .039; 10–14 days post-operative: 15.1 vs. 9.6 d/sc, p = .015).

Conclusion

The liver group was hypercoagulable based on elevated G-values at all time points compared to the control group. This hypercoagulability was attributed to the effect of hepatic tumours alone, and not secondary to surgery and anaesthesia.  相似文献   

8.
BackgroundHepatocellular carcinoma is the most common primary hepatic malignancy in humans and dogs. Several differentially expressed molecules have been studied and reported in human hepatocellular carcinoma and non-neoplastic liver lesions. However, studies on the features of canine hepatocellular carcinoma are limited, especially related to the differential characteristics of neoplastic and non-neoplastic lesions.ObjectivesThe study''s objective was 1) to examine and evaluate the expression of arginase-1, P-glycoprotein, and cytokeratin 19 in canine liver tissues and 2) to investigate the differential features of hepatocellular carcinomas, liver tissue with non-neoplastic lesions, and paracancerous liver tissues in dogs.MethodsThe expression levels of three markers underwent immunohistochemical analysis in 40 non-neoplastic liver tissues, 32 hepatocellular carcinoma tissues, and 11 paracancerous liver tissues. Scoring of each marker was performed semi-quantitatively.ResultsArginase-1 and P-glycoprotein were significantly downregulated in hepatocellular carcinoma, compared with hepatic tissues with non-neoplastic diseases (p < 0.001). Expression levels of arginase-1 and P-glycoprotein were also significantly lower in hepatocellular carcinoma than in paracancerous liver tissues (arginase-1, p = 0.0195; P-glycoprotein, p = 0.047). Few cytokeratin 19-positive hepatocytes were detected and only in one hepatocellular carcinoma and one cirrhotic liver sample.ConclusionsThe results of this study suggest that downregulation of arginase-1 and P-glycoprotein is a feature of canine hepatocellular carcinoma; thus, those markers are potential candidates for use in differentiating hepatocellular carcinomas from non-neoplastic liver lesions in dogs.  相似文献   

9.
10.
The goal of this study was to determine the efficacy and tolerability of gemcitabine in dogs diagnosed with hepatocellular carcinoma (HCC). Eighteen dogs were examined retrospectively (4 massive HCC, 10 nodular HCC and 4 diffuse HCC). All dogs received gemcitabine at 350-400 mg m(-2) weekly for 5 weeks. Toxicity was graded using VCOG-CTCAE guidelines and response was monitored with serial abdominal ultrasounds. Fifteen dogs completed all five cycles. Toxicity was minimal and consisted of grade I/II vomiting, anorexia and diarrhoea and two episodes of grade III neutropenia. Median survival time for all dogs was 983 days. Median progression free interval was 971 days. Based on the results of this study, surgery remains the best treatment for HCC, despite incomplete resection. There was no improvement in the survival of those diagnosed with nonresectable HCC treated with gemcitabine chemotherapy.  相似文献   

11.
JA1体外诱导HCC细胞凋亡的实验研究   总被引:2,自引:1,他引:1  
贾宁  赵丽  方梅 《中国兽医学报》2005,25(3):281-283
采用噻唑蓝(MTT)还原法,测定了梯度浓度的某植物种子粗提物JA1对人肝癌细胞株HCC增殖作用的影响;同时采用流式细胞术、DNA凝胶电泳和透射电子显微镜技术,在体外观察了JA1对HCC细胞凋亡的诱导作用。结果显示,JA1可显著抑制肝癌细胞HCC的增殖,而且这种抑制有浓度依赖性和时间依赖性;流式细胞仪分析表明,经JA1作用后的肝癌细胞HCC检测标本中有明显的DNA低含量颗粒(“亚G1期”峰);凝胶电泳呈现出典型的DNA梯形条带;电镜下出现细胞凋亡典型的形态学改变。  相似文献   

12.
The purpose of this study was to determine the utility of triple‐phase helical computed tomography (CT) for differentiating canine hepatic masses. Seventy dogs with hepatic masses underwent triple‐phase CT followed by surgical removal of the hepatic masses. Triple‐phase helical CT scans for each dog included precontrast, arterial phase, portal venous phase, and delayed phase studies. The removed hepatic masses were histopathologically classified as hepatocellular carcinoma (n = 47), nodular hyperplasia (n = 14), and hepatic metastatic tumors (n = 9) in dogs. Of the 47 hepatocellular carcinomas, the most common CT findings included a heterogeneous pattern with hyper‐, iso‐, and hypoenhancement in both the arterial and portal venous phases (40/47, 85.1%). Of the 14 nodular hyperplasias, the most common CT findings were a homogeneous pattern with hyper‐ and isoenhancement in both the portal venous and delayed phases (13/14, 92.9%). Of nine hepatic metastatic tumors, the most common CT findings included a homogeneous hypoenhancement pattern in both the arterial and portal venous phases (8/9, 88.9%). In addition, 5 (55.6%) showed homogeneous hypoenhancement patterns in the delayed phase. Findings from our study indicated that triple‐phase CT is a useful tool for preoperative differentiation of hepatocellular carcinoma, nodular hyperplasia, and hepatic metastatic tumors in dogs.  相似文献   

13.
It is extremely rare to have multiple spontaneous proliferative lesions in young adult rats. Here, we report the occurrence of different proliferative lesions in multiple tissues of a 7-week-old female rat in a 1-week repeated toxicity study. Grossly, multiple white patches and nodules in the bilateral kidneys, femoral and subcutaneous masses, and a nodule in the liver were observed. Renal lesions were diagnosed as renal mesenchymal tumors. One of the femoral subcutaneous masses was diagnosed as an adenolipoma consisting of mammary epithelial cells and mature adipocytes. The other femoral and abdominal subcutaneous masses were diagnosed as lipomas consisting of mature adipocytes. The liver nodule was diagnosed as non-regenerative hepatocellular hyperplasia, which was characterized by the proliferation of slightly hypertrophic hepatocytes. In the cauda equina, the growth of enlarged Schwann cells around the axon was observed, and this lesion was diagnosed as a neuroma.  相似文献   

14.
Klotho is an anti-ageing gene and is known to act as a tumour suppressor in human hepatocellular carcinoma (HCC). According to a previous study, Klotho is present in normal canine mammary glands, and down-expression in tumours is positively associated with negative prognosis. However, the presence and significance of Klotho in canine HCC has not yet been reported. This study aimed to confirm Klotho expression in normal canine liver tissues using western blotting and immunohistochemistry, and whether the expression differed in non-neoplastic liver disease and HCC. Furthermore, correlation between clinicopathologic features and expression of Klotho was evaluated. All of the normal liver tissues showed the presence of Klotho, and Klotho expression was significantly decreased in the HCC tissue as compared to the non-neoplastic hepatic tissue. Additionally, Klotho expression was significantly associated with tumour size (P = .045), liver enzyme (alanine aminotransferase (ALT)) (P = .018), and metastasis (P = .024). Analysis of the survival curve revealed that reduced Klotho expression was significantly associated with poor disease-free survival (P = .041) in HCC. These results show that Klotho expression is present in normal canine liver tissue and that reduced Klotho expression is associated with poor prognosis in canine HCC. Thus, Klotho was presumed to be a potential clinical prognostic marker for canine HCC.  相似文献   

15.
There is scant literature on primary nonhematopoietic malignant liver tumours (PMLT) in cats. In this retrospective study, medical data of 40 cats diagnosed with PMLT were reviewed over a period of 22 years (2000–2021). The most frequent epithelial tumours were hepatocellular (42.5%) and bile duct carcinomas (32.5%), only six (15%) cats had mesenchymal tumours. The median age was 13 years and clinical signs commonly included ano-/hyporexia (62.5%), apathy/lethargy (52.5%), weight loss (42.5%) and vomiting (35%). At initial diagnosis, metastases were confirmed in 1 (2.5%) and suspected in three (7.5%) cats. Massive was the most frequent morphology (75%). Most intrahepatic tumours were left-sided (54.2%) with the left medial lobe being primarily affected (25%). Extrahepatic tumours were rare (5%). In 34 (85%) cats, liver lobectomy was performed (surgery group), four (10%) were treated palliatively (non-surgery group), and two (5%) received no treatment. Intraoperative complications occurred in 11.8% with four (15.4%) postoperative deaths. Recurrence was detected in 28.6% at a median of 151 days (range, 79–684 days), while postoperative metastases were suspected in 21.4% at a median of 186 days (range, 79–479 days). The median survival time (MST) was significantly longer in cats of the surgery group (375 days) than in the non-surgery group (16 days) (p = .002). MST was 868 days for hepatocellular compared to 270 days for bile duct carcinomas (p = .06). In summary, liver lobectomy is associated with prolonged survival times and good prognosis in cats with hepatocellular, and an acceptable prognosis in cats with bile duct carcinoma.  相似文献   

16.
17.
利用噬菌体环七肽库筛选与肝癌细胞特异性结合的多肽,并对其亲和力进行生物学鉴定。以HL-7702为消减细胞,HepG2为筛选靶细胞,对噬菌体随机环七肽库进行4轮全细胞消减筛选,并随机挑取60个阳性噬菌体克隆,以ELISA法鉴定其与HepG2细胞的结合活性,并取阳性克隆进行测序分析,并合成多肽进行免疫细胞化学染色鉴定。经4轮筛选,噬菌体在靶细胞HepG2上出现明显富集;利用ELISA从随机挑选的60个噬菌体克隆中得到15个与肝癌细胞具有高结合力的阳性克隆,测序并进行序列分析比对发现氨基酸序列无同源性,经免疫细胞化学染色鉴定后,发现1条多肽序列亲和力较高,为提高抗菌肽对肿瘤细胞的靶向杀伤作用奠定基础。  相似文献   

18.
A 7-year-old female Eurasian otter (Lutra lutra) at the Seoul Grand Park, Korea, died after displaying depression, anorexia, weight loss and rough skin for several days. At necropsy, a solitary friable round mass, which was approximately 12 × 9 × 5 cm and mottled dark red and yellow, was found bulging from the right hepatic lobe. Microscopically, the nonencapsulated, poorly circumscribed mass was composed of solid sheets of neoplastic hepatocytes. In addition, numerous small tan foci, ranging from 0.5 to 1.0 cm in diameter, were evenly scattered throughout the pancreatic tissue. These foci were found to be nonencapsulated, well-demarcated hyperplastic nodules of the exocrine pancreatic gland. We observed neither intrahepatic nor extrahepatic metastases. Based on the gross and microscopic changes, we diagnosed the animal as having a hepatocellular adenoma accompanied by exocrine pancreatic nodular hyperplasia.  相似文献   

19.
Hepatic progenitor cells (HPCs) are bipotential stem cells residing in human and animal livers that are able to differentiate towards the hepatocytic or cholangiocytic lineages. HPCs are present in both hepatocellular (HCC) and cholangiocellular carcinoma (CC) in humans; and a small percentage of HCC can originate from cancer stem cells. However, its distribution in canine liver tumour has not been studied. Herein, we searched for stem/progenitor cells in 13 HCC and 7 CC archived samples by immunohistochemical analysis. We found that both liver tumours presented a higher amount of K19‐positive HPCs. Besides, 61.6% of HCC cases presented immature CD44‐positive hepatocytes. Nevertheless, only two cases presented CD133‐positive cells. As observed in humans, hepatic canine tumours presented activated HPCs, with important differentiation onto hepatocytes‐like cells and minimal role of cancer stem cells on HCC. These findings reiterate the applicability of canine model in the search for new therapies before application in humans.  相似文献   

20.
贾宁  方梅 《中国兽医学报》2007,27(5):710-714
采用噻唑蓝(MTT)还原法测定梯度浓度的沙冬青提取物(JA1)对体外培养小鼠肝癌细胞株H22增殖的影响;同时对皮下移植肿瘤H22小鼠灌服不同剂量的JA1以检测抑瘤率,进一步采用流式细胞术、光镜和透射电子显微镜技术,检测和观察JA1对小鼠移植性肿瘤H22的诱导凋亡作用。结果显示,JA1可显著抑制体外培养小鼠肝癌H22细胞的增殖,并且这种抑制存在浓度和时间关系。同时,JA1对小鼠皮下移植性肿瘤H22也有明显的抑制作用。流式细胞分析表明,JA1灌胃试验组瘤组织细胞DNA直方图上见有明显的凋亡峰;在光镜和电镜下,JA1灌胃试验组也见有明显的瘤细胞凋亡,表明JA1对体内、外H22细胞的增殖抑制是以诱导凋亡为基础的。  相似文献   

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