Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
Add more filters











Publication year range
1.
Vet Radiol Ultrasound ; 63(6): 661-674, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36189784

ABSTRACT

This consensus statement is designed to provide a standard of care document and describes the ACVR and ECVDI definition for performing a standard abdominal ultrasound examination in dogs and cats. The ACVR and ECVDI define a standard abdominal ultrasonographic examination as a complete exam of the abdominal organs which is appropriately documented. The consensus statement intends to provide guidance to veterinary sonographers and veterinarians for the performance and documentation of high-quality diagnostic ultrasound examination. The document may also serve as a teaching aid for veterinary students, veterinarians, and residents in diagnostic imaging who seek proficiency in diagnostic ultrasound. Finally, it may serve an additional role in educating the public as to what a high-quality abdominal ultrasound examination should entail.


Subject(s)
Cat Diseases , Dog Diseases , Cats , Dogs , Animals , Dog Diseases/diagnosis , Ultrasonography/veterinary , Ultrasonography/methods , Abdomen/diagnostic imaging , Reference Standards
2.
Vet Radiol Ultrasound ; 52(6): 591-5, 2011.
Article in English | MEDLINE | ID: mdl-21831251

ABSTRACT

We compared the accuracy of five veterinary radiologists when reading 20 radiographic cases on both analog film and in camera-digitized format. In addition, we compared the ability of five veterinary radiologists vs. 10 private practice veterinarians to interpret the analog images. Interpretation accuracy was compared using receiver operating characteristic curve analysis. Veterinary radiologists' accuracy did not significantly differ between analog vs. camera-digitized images (P = 0.13) although sensitivity was higher for analog images. Radiologists' interpretation of both digital and analog images was significantly better compared with the private veterinarians (P < 0.05).


Subject(s)
Cat Diseases/diagnostic imaging , Dog Diseases/diagnostic imaging , Radiographic Image Enhancement/methods , Radiographic Image Enhancement/standards , Radiology/statistics & numerical data , Veterinarians/statistics & numerical data , Analysis of Variance , Animals , Cats , Dogs , Photography , Radiology/methods , Radiology/standards , Referral and Consultation , Reproducibility of Results , Sensitivity and Specificity , Societies, Scientific , Surveys and Questionnaires
3.
J Am Vet Med Assoc ; 234(6): 771-6, 2009 Mar 15.
Article in English | MEDLINE | ID: mdl-19284343

ABSTRACT

OBJECTIVE: To determine signalment, history, and outcome of cats with gastrointestinal tract intussusception and to identify physical examination, diagnostic imaging, surgical, histologic, and necropsy findings in affected cats. DESIGN: Retrospective case series. ANIMALS: 20 cats with intussusception. PROCEDURES: Medical records were evaluated for information on signalment; history; physical examination, diagnostic imaging, surgical, histologic, and necropsy findings; and outcome. RESULTS: Ten cats were < 1 year old, and 9 were >or= 6 years old. Anorexia (14/17), lethargy (12/17), and vomiting (12/17) were the most common reasons for examination. Dehydration (13/18), poor body condition (12/18), signs of abdominal pain (8/18), and an abdominal mass (8/18) were the most common physical examination findings. Abdominal radiography revealed intestinal obstruction in all 10 cats in which it was performed; abdominal ultrasonography revealed intussusception in all 7 cats in which it was performed. The most common intussusception was jejuno-jejunal (8/20), and no intussusceptions were found proximal to the duodenum. Eleven of 13 cats that underwent laparotomy required intestinal resection and anastomosis. Histologic examination revealed intestinal lymphoma or inflammatory bowel disease in 7 of 8 cats >/= 6 years old and idiopathic intussusception in 7 of 8 cats < 1 year old. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in cats, intussusception has a bimodal age distribution, is most commonly jejuno-jejunal, often requires surgical resection and anastomosis, is often associated with alimentary lymphoma or inflammatory bowel disease in older cats, and is readily diagnosed by means of ultrasonography.


Subject(s)
Cat Diseases/surgery , Intussusception/veterinary , Jejunum/pathology , Age Factors , Anastomosis, Surgical/veterinary , Animals , Cat Diseases/diagnostic imaging , Cat Diseases/pathology , Cats , Female , Inflammatory Bowel Diseases/diagnostic imaging , Inflammatory Bowel Diseases/pathology , Inflammatory Bowel Diseases/surgery , Inflammatory Bowel Diseases/veterinary , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/pathology , Intestinal Obstruction/surgery , Intestinal Obstruction/veterinary , Intussusception/diagnostic imaging , Intussusception/pathology , Intussusception/surgery , Jejunum/diagnostic imaging , Jejunum/surgery , Male , Retrospective Studies , Ultrasonography
4.
Clin Cancer Res ; 11(9): 3543-52, 2005 May 01.
Article in English | MEDLINE | ID: mdl-15867258

ABSTRACT

PURPOSE: To monitor tumor blood flow noninvasively during photodynamic therapy (PDT) and to correlate flow responses with therapeutic efficacy. EXPERIMENTAL DESIGN: Diffuse correlation spectroscopy (DCS) was used to measure blood flow continuously in radiation-induced fibrosarcoma murine tumors during Photofrin (5 mg/kg)/PDT (75 mW/cm2, 135 J/cm2). Relative blood flow (rBF; i.e., normalized to preillumination values) was compared with tumor perfusion as determined by power Doppler ultrasound and was correlated with treatment durability, defined as the time of tumor growth to a volume of 400 mm3. Broadband diffuse reflectance spectroscopy concurrently quantified tumor hemoglobin oxygen saturation (SO2). RESULTS: DCS and power Doppler ultrasound measured similar flow decreases in animals treated with identical protocols. DCS measurement of rBF during PDT revealed a series of PDT-induced peaks and declines dominated by an initial steep increase (average +/- SE: 168.1 +/- 39.5%) and subsequent decrease (59.2 +/- 29.1%). The duration (interval time; range, 2.2-15.6 minutes) and slope (flow reduction rate; range, 4.4 -45.8% minute(-1)) of the decrease correlated significantly (P = 0.0001 and 0.0002, r2= 0.79 and 0.67, respectively) with treatment durability. A positive, significant (P = 0.016, r2= 0.50) association between interval time and time-to-400 mm3 was also detected in animals with depressed pre-PDT blood flow due to hydralazine administration. At 3 hours after PDT, rBF and SO2 were predictive (P < or = 0.015) of treatment durability. CONCLUSION: These data suggest a role for DCS in real-time monitoring of PDT vascular response as an indicator of treatment efficacy.


Subject(s)
Neoplasms, Radiation-Induced/physiopathology , Sarcoma, Experimental/physiopathology , Spectroscopy, Near-Infrared/methods , Animals , Blood Flow Velocity/drug effects , Dihematoporphyrin Ether/therapeutic use , Mice , Mice, Inbred C3H , Neoplasm Transplantation , Neoplasms, Radiation-Induced/diagnostic imaging , Neoplasms, Radiation-Induced/drug therapy , Oxygen/metabolism , Photochemotherapy , Prognosis , Sarcoma, Experimental/diagnostic imaging , Sarcoma, Experimental/drug therapy , Treatment Outcome , Ultrasonography, Doppler/methods
5.
Vet Radiol Ultrasound ; 46(1): 27-32, 2005.
Article in English | MEDLINE | ID: mdl-15693555

ABSTRACT

Helical computed tomographic (CT) angiography was performed in 16 dogs with known or suspected portosystemic shunts. Fifteen portosystemic shunts were detected including five single intrahepatic shunts, five single extrahepatic shunts, and five multiple extrahepatic shunts. One dog had a normal CT examination. All diagnoses were confirmed by one or several alternate methods including ultrasound, surgery, necropsy, angiography, and liver biopsy. CT detected the origin of 13 of 15 portosystemic shunts and insertion of 13 of 15 shunts. Limitations included inability to resolve two vessels originating very close to each other, and identification of vessels that traveled parallel to the axial image plane. CT angiography is a promising, minimally invasive method of diagnosing a variety of portosystemic shunts in dogs.


Subject(s)
Angiography/veterinary , Dog Diseases/diagnostic imaging , Hypertension, Portal/veterinary , Portal System/abnormalities , Tomography, X-Ray Computed/veterinary , Animals , Dog Diseases/epidemiology , Dogs , Female , Hypertension, Portal/diagnostic imaging , Male , Philadelphia/epidemiology , Predictive Value of Tests
6.
Am J Vet Res ; 66(1): 21-9, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15691031

ABSTRACT

OBJECTIVE: To investigate subjective and computerized methods of evaluation of color Doppler (CD) and power Doppler (PD) ultrasonographic images (obtained before and after administration of contrast medium) for quantitative assessment of vascularity and perfusion of various naturally occurring tumors in dogs. SAMPLE POPULATION: 34 tumors in 34 dogs. PROCEDURE: Tumors in dogs were examined via CD and PD ultrasonography before and after i.v. injection of a microbubble contrast agent (pre- and postcontrast examinations, respectively). Images were digitized for subjective assessment of vessel density and vascular pattern and computer-aided assessment of parameters of vascularity (fractional area [FA]) and perfusion (color-weighted FA [CWFA] and mean color-weighted FA [CWFA] and mean color level). RESULTS: With both analysis methods, more vessels were identified in precontrast PD ultrasonographic images than in precontrast CD ultrasonographic images. Moreover, compared with values for precontrast PD ultrasonography, FA, CWFA, and mean color level were higher for postcontrast PD ultrasonography. In postcontrast images, there was a significant association between vessel densities determined through subjective and computerized assessments. Although sample size was small, vascularity of squamous cell carcinomas was significantly greater than that of other tumor types. Ten of the 19 softer than issue that sarcomas had low vessel density with minor contrast enhancement. With increasing gross tumor volume, FA and CWFA decreased for all Doppler ultrasonographic methods. CONCLUSIONS AND CLINICAL RELEVANCE: Higher values of the ultrasonographic parameters representing vascularity and perfusion of tumors in dogs were determined via PD ultrasonography after administration of contrast medium than via PD or CD ultrasonography without administration of contrast medium.


Subject(s)
Dog Diseases/diagnostic imaging , Neoplasms/veterinary , Ultrasonography, Doppler/methods , Animals , Contrast Media , Dogs , Female , Male , Neoplasms/blood supply , Neoplasms/diagnostic imaging , Ultrasonography, Doppler/veterinary , Ultrasonography, Doppler, Color/veterinary
7.
J Am Vet Med Assoc ; 225(6): 861-7, 2004 Sep 15.
Article in English | MEDLINE | ID: mdl-15485044

ABSTRACT

OBJECTIVE: To evaluate early medical and behavioral effects of deployment to the World Trade Center, Fresh Kills Landfill, or the Pentagon on responding search-and-rescue (SAR) dogs. DESIGN: Prospective double cohort study. ANIMALS: The first cohort included SAR dogs responding to the September 11, 2001, terrorist attacks (deployed), and the second cohort included SAR dogs trained in a similar manner but not deployed (controls). Enrollment occurred from October 2001 to June 2002. PROCEDURE: Dogs were examined by their local veterinarians; thoracic radiographs and blood samples were shipped to the University of Pennsylvania for analysis. Handlers completed medical and training histories and a canine behavioral survey. RESULTS: Deployed dogs were older and had more search experience than control dogs. Serum concentrations of globulin and bilirubin and activity of alkaline phosphatase were significantly higher in deployed dogs, independent of age and training. Despite significant differences in several blood parameters, values for both groups were within reference ranges. No pulmonary abnormalities were detected on radiographs, and no significant differences in behavior or medical history were detected between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Within the first year following the September 11 attacks, there was no evidence that responding dogs developed adverse effects related to their work. Mild but significantly higher serum concentrations of globulin and bilirubin and activity of alkaline phosphatase in deployed dogs suggested higher antigen or toxin exposure. These dogs will be monitored for delayed effects for at least 3 years.


Subject(s)
Behavior, Animal/physiology , Dogs/physiology , Occupational Diseases/veterinary , Rescue Work/methods , Sentinel Surveillance/veterinary , Age Factors , Alkaline Phosphatase/metabolism , Animals , Bilirubin/blood , Cohort Studies , District of Columbia/epidemiology , Dogs/blood , Dogs/metabolism , Female , Globulins/analysis , Male , New York City/epidemiology , Occupational Diseases/epidemiology , Occupational Exposure , Prospective Studies , Reference Values , Terrorism , Time Factors
8.
Vet Radiol Ultrasound ; 45(3): 205-9, 2004.
Article in English | MEDLINE | ID: mdl-15200256

ABSTRACT

Retrospectively, 243 dogs with radiographic evidence of gastric dilatation-volvulus (GDV) were studied for radiographic signs of pneumatosis (intramural gas), pneumoperitoneum, splenomegaly, and severity of gastric distention. The sensitivity, specificity, and predictive value of these imaging signs as predictors of gastric wall necrosis, as determined by visual inspection at surgery or necropsy, were determined. The sensitivity and specificity of gastric pneumatosis were 14.1% and 92.7%, respectively. The prevalence of gastric wall necrosis was 26.6%. The positive and negative predictive values of gastric pneumatosis for predicting gastric necrosis were 40.9% and 74.9%, respectively. Gastric pneumatosis and pneumoperitoneum were identified together in four dogs. Pneumoperitoneum, either alone or in conjunction with pneumatosis, yielded similar results as a test for gastric necrosis. Splenomegaly and severity of gastric distention were insensitive and nonspecific for gastric wall necrosis. Splenomegaly did not predict the need for splenectomy at surgery. Although pneumatosis and pneumoperitoneum are relatively specific signs of gastric wall necrosis, the utility of these signs as a test for gastric necrosis is limited in clinical practice. The significance of pneumatosis should be taken into consideration with previous treatments for gastric decompression, as percutaneous gastric trocharization or orogastric intubation may increase the number of false-positive results.


Subject(s)
Gastric Dilatation/veterinary , Pneumoperitoneum/veterinary , Radiography, Abdominal/veterinary , Stomach Volvulus/veterinary , Animals , Dogs , Female , Gastric Dilatation/complications , Gastric Dilatation/diagnostic imaging , Male , Pneumoperitoneum/complications , Pneumoperitoneum/diagnostic imaging , Predictive Value of Tests , Radiography, Abdominal/methods , Records/veterinary , Retrospective Studies , Sensitivity and Specificity , Stomach Volvulus/complications , Stomach Volvulus/diagnostic imaging
9.
J Am Vet Med Assoc ; 223(4): 469-74, 2003 Aug 15.
Article in English | MEDLINE | ID: mdl-12930084

ABSTRACT

OBJECTIVE: To characterize clinical, clinicopathologic, radiographic, and ultrasonographic findings in cats with histologically confirmed acute necrotizing pancreatitis (ANP) or chronic nonsuppurative pancreatitis (CP) and identify features that may be useful in the antemortem differentiation of these disorders. DESIGN: Retrospective study. ANIMALS: 63 cats with histologically confirmed ANP (n = 30) or CP (33). PROCEDURE: Medical records were reviewed for signalment, clinical signs, concurrent diseases, clinicopathologic findings, and results of radiography and ultrasonography. RESULTS: Cats in both groups had similar nonspecific clinical signs, physical examination findings, and radiographic and ultrasonographic abnormalities. Abdominal ultrasonographic abnormalities, including hypoechoic pancreas, hyperechoic mesentery, and abdominal effusion, were found in cats in both groups and, therefore, were not specific for ANP. Cats with CP were significantly more likely to have concurrent diseases than were cats with ANP (100 and 83%, respectively). Clinicopathologic abnormalities were similar between groups; however, serum alanine aminotransferase and alkaline phosphatase activities were significantly higher in cats with CP. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that ANP and CP in cats cannot be distinguished from each other solely on the basis of history, physical examination findings, results of clinicopathologic testing, radiographic abnormalities, or ultrasonographic abnormalities.


Subject(s)
Cat Diseases/diagnosis , Pancreas/pathology , Pancreatitis, Acute Necrotizing/veterinary , Pancreatitis/veterinary , Animals , Cat Diseases/diagnostic imaging , Cats , Chronic Disease , Diagnosis, Differential , Female , Male , Pancreas/diagnostic imaging , Pancreatitis/diagnosis , Pancreatitis/diagnostic imaging , Pancreatitis, Acute Necrotizing/diagnosis , Pancreatitis, Acute Necrotizing/diagnostic imaging , Physical Examination/veterinary , Radiography, Abdominal/veterinary , Retrospective Studies , Serologic Tests/veterinary , Ultrasonography
10.
Vet Radiol Ultrasound ; 44(6): 636-41, 2003.
Article in English | MEDLINE | ID: mdl-14703242

ABSTRACT

Preoperative knowledge of the renal vascular anatomy is important for selection of the appropriate feline renal donor. Intravenous urograms (IVUs) have been performed routinely to screen potential donors at the Veterinary Hospital of the University of Pennsylvania (VHUP), but the vascular phase views lack sufficient detail of the renal vascular anatomy. Computed tomography angiography (CTA), which requires a helical computed tomography (CT) scanner, has been found to provide superior renal vascular anatomic information of prospective human renal donors. The specific aims of this study were as follows: 1) develop the CTA technique for the feline patient; and 2) obtain preliminary information on feline renal vessel anatomy in potential renal donors. Ten healthy, potential feline renal donors were anesthetized and imaged using a third-generation helical CT scanner. The time delay between i.v. contrast medium injection and image acquisition, and other parameters of slice collimation, slice interval, pitch, exposure settings, and reconstruction algorithms were varied to maximize contrast medium opacification of the renal vascular anatomy. Optimal CTA acquisition parameters were determined to be: 1) 10-sec delay post-i.v. bolus of iodinated contrast medium; 2) two serially acquired (corresponding to arterial and venous phases) helical scans through the renal vasculature; 3) pitch of 2 (4 mm/sec patient translation, 2 mm slice collimation); and 4) 120-kVp, 160-mA, and 1-sec exposure settings. Retrospective reconstructed CTA transverse images obtained at a 2-mm slice width and a 1-mm slice interval in combination with two-dimensional reformatted images and three-dimensional reconstructed images were qualitatively evaluated for vascular anatomy; vascular anatomy was confirmed at surgery. Four cats had single renal arteries and veins bilaterally; four cats had double renal veins. One cat had a small accessory artery supplying the caudal pole of the left kidney. One cat had a left renal artery originating from the aorta at a 90 degrees angle with the cranial mesenteric artery. CTA of the feline renal vascular anatomy is feasible, and reconstruction techniques provide excellent anatomic vascular detail. CTA is now used routinely at VHUP to screen all potential feline renal donors.


Subject(s)
Cats/anatomy & histology , Kidney/diagnostic imaging , Renal Artery/diagnostic imaging , Renal Veins/diagnostic imaging , Tomography, X-Ray Computed/veterinary , Angiography/methods , Angiography/veterinary , Animals , Cat Diseases/surgery , Contrast Media/administration & dosage , Infusions, Intravenous/veterinary , Iohexol/administration & dosage , Kidney/anatomy & histology , Kidney/blood supply , Kidney Function Tests/veterinary , Kidney Transplantation/veterinary , Male , Prospective Studies , Renal Artery/anatomy & histology , Renal Artery/physiology , Renal Veins/anatomy & histology , Renal Veins/physiology , Tissue Donors , Tomography, X-Ray Computed/methods
11.
In Vivo ; 16(6): 431-7, 2002.
Article in English | MEDLINE | ID: mdl-12494886

ABSTRACT

BACKGROUND: Poor tumour oxygenation is associated with radiation resistance. The recording of pre-treatment oxygenation status has been shown to be of prognostic relevance. MATERIAL AND METHODS: Eleven dogs with spontaneously arising soft tissue sarcomas were included in this study. Oxygen partial pressure measurements (pO2) were performed with the Eppendorf method. RESULTS: The mean of median pO2 was 9.6 mmHg (range: 0.1-30 mmHg). Four of the nine dogs included in the statistical analysis showed a median pO2 < or = 2.5 mmHg. The natural logarithm of the hypoxic subvolume correlated with the hypoxic fraction < or = 2.5 mmHg (p = 0.0712) and < or 5 mmHg (p = 0.0988). Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated significantly to several oxygen parameters. CONCLUSION: Hypoxia exists in spontaneous canine soft tissue sarcomas and the dog can be used as a reliable model for repeated oxygenation measurements. Ultrasonography assures reliability of needle placement.


Subject(s)
Dog Diseases/metabolism , Oxygen/metabolism , Sarcoma/veterinary , Soft Tissue Neoplasms/veterinary , Animals , Blood Gas Monitoring, Transcutaneous/veterinary , Dog Diseases/radiotherapy , Dogs , Ion-Selective Electrodes , Neoplasm Staging/veterinary , Polarography/veterinary , Prognosis , Radiotherapy/veterinary , Sarcoma/metabolism , Sarcoma/radiotherapy , Soft Tissue Neoplasms/metabolism , Soft Tissue Neoplasms/radiotherapy , Ultrasonography/veterinary
12.
J Am Vet Med Assoc ; 221(12): 1724-30, 2002 Dec 15.
Article in English | MEDLINE | ID: mdl-12494970

ABSTRACT

OBJECTIVE: To determine ultrasonographic findings in cats with clinical, gross pathologic, and histologic evidence of acute pancreatic necrosis. DESIGN: Retrospective study. ANIMALS: 20 cats. PROCEDURE: Ultrasound reports and permanent ultrasonographic images were reviewed, and ultrasonographic findings were recorded. Thoracic and abdominal radiographs were also reviewed, when available. Anatomic localization of pancreatic necrosis was determined from the gross pathology report; duration and severity of pancreatic necrosis were determined by reviewing histologic specimens. The presence of concurrent disease was recorded from the final pathology report. RESULTS: The pancreas was considered ultrasonographically normal in 10 cats and was not observed in 3. Ultrasonographic findings were considered compatible with pancreatitis in the remaining 7 cats. Gross pathologic findings indicated that pancreatitis was multifocal in all 7 of these cats; histologically, pancreatitis was acute or subacute in 5 and associated with severe or moderate necrosis in 6. In the remaining 13 cats, gross pathologic findings indicated that pancreatitis was multifocal (n = 8) or focal (2), or gross pathologic findings were normal (3). Histologically, pancreatitis was peracute or acute in 11 of these 13 cats and associated with severe or moderate necrosis in 8. Thoracic and abdominal radiographic findings were nonspecific. CONCLUSIONS AND CLINICAL RELEVANCE: Results of ultrasonography were consistent with a diagnosis of pancreatitis in only 7 of 20 cats with acute pancreatic necrosis in the present study. This suggests that new diagnostic criteria must be established if abdominal ultrasonography is to be an effective tool in the diagnosis of pancreatitis in cats.


Subject(s)
Cat Diseases/diagnostic imaging , Pancreas/pathology , Pancreatitis/veterinary , Acute Disease , Animals , Cat Diseases/diagnosis , Cat Diseases/pathology , Cats , Female , Male , Necrosis , Pancreatitis/diagnosis , Pancreatitis/diagnostic imaging , Pancreatitis/pathology , Radiography, Abdominal/veterinary , Retrospective Studies , Ultrasonography
14.
Cancer Res ; 62(10): 2962-70, 2002 May 15.
Article in English | MEDLINE | ID: mdl-12019179

ABSTRACT

In tumors, rapid cell proliferation associated with deficient vascularization leads to areas of hypoxia. Tumor hypoxia has direct consequences on clinical and prognostic parameters and is a potential therapeutic target. The hypoxic response depends critically on hypoxia-inducible factor-1alpha (HIF-1alpha) in pathological (e.g., tumorigenesis) as well as physiological (e.g., development and wound healing) processes. By s.c. injection of HIF-1alpha(-/-) embryonic stem (ES) cells in nude mice, we were able to demonstrate the role of HIF-1alpha in cell differentiation of teratocarcinomas. HIF-1alpha(+/+) tumors grow fast and preferentially form neuronal tissue, whereas HIF-1alpha(-/-) tumors show delayed growth and favorably form mesenchyme-derived tissue. Mixing wild-type and HIF-1alpha(-/-) ES cells in the same tumor at a ratio as low as 1:100, we showed that HIF-1alpha(+/+) cells can rescue the growth of mixed tumors although these tumors are not significantly different phenotypically or genotypically from the original HIF-1alpha(-/-) tumors. Interestingly, these results are not restricted to teratocarcinomas: they were confirmed with mixtures of Hepa1/Hepa1C4 cells (where HIF-1beta is mutated), demonstrating that growth changes are not related to differences in differentiation observed within teratocarcinomas. We also showed that despite lower mRNA expression, vascular endothelial growth factor protein status in HIF-1alpha(-/-) and mixed tumors does not significantly differ from the HIF-1alpha(+/+) tumors. Moreover, we demonstrated that tumor vascularization remains proportional to vascular endothelial growth factor protein levels, but that hypoxic up-regulation of this growth factor is not the decisive factor influencing tumor growth. Differences in levels of apoptosis are not responsible for alteration in growth because poly(ADP-ribose) polymerase cleavage, a hallmark of the apoptotic process, was similar in HIF-1alpha(+/+), HIF-1alpha(-/-), and mixed tumors. Our data demonstrate that the HIF-1alpha-dependent response of a few cells is capable of sustaining the growth of the whole tumor, probably through the secretion of factors up-regulated under low oxygen conditions.


Subject(s)
Cell Transformation, Neoplastic/pathology , Endothelial Growth Factors/physiology , Lymphokines/physiology , Teratocarcinoma/pathology , Transcription Factors/deficiency , Animals , Apoptosis/physiology , Cell Differentiation/physiology , Cell Division/physiology , Cell Hypoxia/physiology , Endothelial Growth Factors/biosynthesis , Endothelial Growth Factors/genetics , Female , Hypoxia-Inducible Factor 1, alpha Subunit , Lymphokines/biosynthesis , Lymphokines/genetics , Mice , Mice, Inbred BALB C , Mice, Nude , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Stem Cells/cytology , Stem Cells/physiology , Teratocarcinoma/blood supply , Teratocarcinoma/metabolism , Transcription Factors/genetics , Transcription Factors/physiology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
15.
Cancer Res ; 62(3): 747-55, 2002 Feb 01.
Article in English | MEDLINE | ID: mdl-11830529

ABSTRACT

We examined the ability of recombinant murine interleukin-12 (rmIL-12) to inhibit the vasculature and growth of mammary carcinomas arising in situ in mouse mammary tumor virus (MMTV)-infected female C3H/HeN mice. Although it is a potent antiangiogenic and antitumor agent in many transplanted murine tumor models, rmIL-12 failed to inhibit the vascularity, reduce the perfusion, or alter the growth of these autochthonous carcinomas. Factors intrinsic to these tumor cells were unlikely to be responsible for therapy failure. This is because primary cells derived from these carcinomas responded to IFN-gamma, and rmIL-12 was effective against transplanted tumors arising from Mm5MT cells, a line established from a MMTV-induced mammary carcinoma in C3H mice. Factors intrinsic to the mice that host the autochthonous mammary carcinomas were also not responsible for failure, because they sponsored rmIL-12 antiangiogenic and antitumor effects against transplanted K1735 murine melanoma tumors. Instead, the autochthonous nature of the mammary carcinomas and their possession of a high percentage of mature, pericyte-covered vessels that are resistant to therapeutic regression may be responsible. This is supported by the observation that transplanted Mm5MT tumors had a lower proportion of pericyte-covered vessels and responded to rmIL-12 therapy. These results point to significant differences between the vasculature of transplanted and autochthonous murine tumors and indicate that their susceptibility to antivascular therapy may differ substantially.


Subject(s)
Interleukin-12/pharmacology , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/virology , Mammary Tumor Virus, Mouse , Neovascularization, Pathologic/prevention & control , Animals , Cell Division/drug effects , Disease Models, Animal , Female , Mammary Neoplasms, Experimental/blood supply , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Inbred C3H , Neoplasm Transplantation , Recombinant Proteins/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL