Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment; however, most ... more Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment; however, most canine reports are case series. This case-control study examined risk factors for SHC in dogs with lymphoma receiving oral cyclophosphamide. Twenty-two dogs with SHC and 66 control dogs were identified. On univariate analysis, SHC risk factors included age (P = 0.041), induction protocol (P = 0.021) and cumulative cyclophosphamide dose (P = 0.002). On multivariate analysis, increasing cumulative cyclophosphamide dose was associated with increased risk of SHC and the 'short' induction protocol (protocol 1) was associated with decreased risk. Controlling for age and induction protocol, odds of SHC increased by 2.21 per 750 mg m −2 increase in cyclophosphamide dose (P = 0.001). SHC from oral cyclophosphamide is a predominately delayed toxicity resulting from high cumulative doses.
Journal of The American Animal Hospital Association, Jul 1, 2014
Inside the Brachycephalic Nose: Conchal Regrowth and Mucosal Contact Points After Laser-Assisted ... more Inside the Brachycephalic Nose: Conchal Regrowth and Mucosal Contact Points After Laser-Assisted Turbinectomy Riccarda Schuenemann, and Gerhard Oechtering This prospective observational study analyzed conchal regrowth after laser-assisted turbinectomy (LATE) in brachycephalic dogs and the mucosal contact of regrown conchae. Eighty brachycephalic dogs (41 pugs, 39 French bulldogs [FBs]) that underwent LATE because of obstructing conchae were evaluated by endoscopy 7 days and 6 mo after surgery. At 6 mo, 96% of FBs' and 65% of pugs' nasal cavities showed regrowth of turbinates. FBs showed higher growth grades than pugs. Revision surgery because of reobstructing regrowth was required in the nasal cavities of 17% of FBs and 3% of pugs. The mean number of contact points reduced from 3.0 in FB and 1.7 in pugs before surgery to 1.2 in FB and 0.2 in pugs after conchal regrowth. Recollapse of nares after surgery significantly influenced the frequency of reoccurrence of contact points. LATE was proven to be an effective treatment of intranasal obstruction caused by mucosal contact between conchae. Conchal regrowth commonly occurs after surgical removal, but the new conchae cause less obstruction due to a significant reduction in number of contact points. Revision surgery because of reobstruction is rarely necessary. The important physiologic functions of conchae make nonobstructing regrowth desirable.
Veterinary Clinics of North America-small Animal Practice, May 1, 2003
Mammary gland tumors are common in the older female dog. Approximately 50% of mammary gland tumor... more Mammary gland tumors are common in the older female dog. Approximately 50% of mammary gland tumors are benign and the other half are malignant (most commonly carcinomas). The development of mammary gland tumors is found to be hormone dependent in dogs. Therefore, the risk for developing these tumors is greatly reduced with early spaying. Spaying after two years of age or more than three heat cycles does not reduce the risk for malignant tumors; however, the spaying of intact dogs is recommended at the time of tumor removal.
ABSTRACT Hyperspectral imaging is an emerging technology in the field of biomedical engineering w... more ABSTRACT Hyperspectral imaging is an emerging technology in the field of biomedical engineering which may be used as a noninvasive modality to characterize tumors. In this paper, a hyperspectral imaging system was used to characterize canine mammary tumors of unknown histopathology (pre-surgery) and correlate these results with the post-surgical histopathology results. The system consisted of a charge coupled device (CCD) camera, a liquid crystal tunable filter in the near infrared range (650-1100 nm) and a controller. Spectral signatures of malignant and benign canine mammary tumors were extracted and analyzed. The reflectance intensities of malignant tumor spectra were generally lower than benign tumor spectra over the entire wavelength range. Previous studies have shown that cancerous tissues have a higher hemoglobin and water content, and lower lipid concentration with respect to benign tissues. The decreased reflectance intensity observed for malignant tumors is likely due to the increased microvasculature and therefore higher blood content of malignant tissue relative to benign tissue. Peaks at 700, 840, 900 and 970 nm were observed in the second derivative absorption spectra, these peaks were attributed to deoxy-hemoglobin, oxy-hemoglobin, lipid and water respectively. A ‘Tissue Optical Index’ was developed that enhances contrast between malignant and benign canine tumors. This index is based on the ratio of the reflectance intensity values corresponding to the wavelengths associated with the four chromophores. Preliminary results from 22 canine mammary tumors showed that the sensitivity and specificity of the proposed method is 85.7% and 94.6% respectively. These results show promise in the non-invasive optical diagnosis of canine mammary cancer.
Journal of the American Animal Hospital Association, 2018
A 2 yr old male castrated golden retriever was evaluated for a rapidly progressing maxillofacial ... more A 2 yr old male castrated golden retriever was evaluated for a rapidly progressing maxillofacial spindle cell tumor. On examination, an ill-defined left maxillary mass, a 2 cm swelling under the left eye, and an enlarged left mandibular lymph node were noted. The dog was bright and alert but appeared painful upon jaw extension. Cytology from the lymph node revealed metastatic disease. Thoracic radiographs and computed tomography scan revealed pulmonary nodules. Computed tomography of the head and neck revealed a 6.7 × 4.1 × 6.5 cm mass at the rostral aspect of the left zygomatic arch invading the orbit. A second opinion of the biopsy specimen in conjunction with positive immunohistochemical staining for desmin led to a revised diagnosis of rhabdomyosarcoma. Treatment consisted of three doses of palliative radiation therapy, in 8 Gy fractions, and chemotherapy with vincristine, cyclophosphamide, and doxorubicin. A rapid clinical response was noted shortly after treatment initiation; ...
Small to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory... more Small to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory surgery with no prior history of pulmonary disease. Initial response to several chemotherapy regimens was poor, but a long-term remission was achieved with CCNU (lomustine) and corticosteroid therapy. After receiving a total cumulative CCNU dose of 552 mg m − 2 over 12 months, an acute episode of respiratory distress occurred and the cat died. Necropsy identifi ed severe diffuse pulmonary fi brosis and no signs of lymphoma. This is the fi rst report of pulmonary fi brosis following high cumulative dose nitrosourea chemotherapy in a cat.
The epithelial-mesenchymal transition (EMT) is a dynamic process linked to metastasis in many tum... more The epithelial-mesenchymal transition (EMT) is a dynamic process linked to metastasis in many tumor types, including mammary tumors. In this study, we evaluated E-cadherin and vimentin immunolocalization in primary canine mammary carcinomas (20 cases) and their respective metastases, as well as their relationship with the core regulators SNAIL/SLUG. To assess the number of cells undergoing the process of EMT, we quantitated double-positive (E-cadherin þ /vimentin þ) cells using immunofluorescence, via cell counting and image analysis. In addition, SNAIL/SLUG expression was evaluated by established immunohistochemical methods. Primary tumors had significantly more E-cadherin þ /vimentin þ co-expression than their paired respective lymph node or distant metastasis, respectively. Furthermore, the percentage of E-cadherin þ /vimentin þ cells in grade II and III carcinomas was significantly higher than in grade I tumors. Primary tumors had significantly higher SNAIL/SLUG expression when analyzed based on the percentage of positive cells compared with their respective distant metastases in pairwise comparisons. An inverse correlation was noted between SNAIL/SLUG immunoreactivity and percentage of E-cadherin þ /vimentin þ immunopositive cells in primary tumor samples when SNAIL/SLUG immunoreactivity was grouped into 2 categories (high versus low) based on percentage-positive staining. These results show a positive correlation between E-cadherin þ /vimentin þ cells and higher tumor grade, establish differences between primary tumor and their respective metastases, and provide further support that EMT plays a critical role in the metastasis of canine mammary carcinoma. Furthermore, these data suggest that modulation of this process could provide greater therapeutic control and provide support for further research to determine if E-cadherin þ /vimentin þ co-immunoreactivity imparts predictive value in the clinical outcome of patients with canine mammary carcinomas.
Journal of Feline Medicine and Surgery, Apr 1, 2009
This study examined the efficacy of doxorubicin-based chemotherapy used for rescue therapy in ref... more This study examined the efficacy of doxorubicin-based chemotherapy used for rescue therapy in refractory feline lymphoma. Records of 23 cats with lymphoma treated with chemotherapy who received doxorubicin for the first time in a rescue setting were reviewed. Seventeen (74%) of the 23 cats had only one treatment of doxorubicin. Five (22%) of the 23 cats had a positive response to doxorubicin and were given additional doses. The response to therapy in 4/5 of these responders could be assessed objectively, of which, two cats (9%) achieved partial remission (PR) and two cats (9%) achieved complete remission (CR). The two cats that achieved CR had differing response durations (6 weeks and greater than 47 months). Three of these five (60%) responders had also received concurrent other chemotherapy in addition to doxorubicin. Cell type and the use of concurrent chemotherapy were significant predictors of response. Cats with small-medium cell lymphomas (P ¼ 0.001) and cats that received concurrent chemotherapy with doxorubicin rescue (P ¼ 0.007) were more likely to respond favorably. This study suggests that doxorubicin-based chemotherapy is not an effective rescue protocol for feline lymphoma.
In spite of major advances over the past several decades in diagnosis and treatment, breast cance... more In spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived crosslinks was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.
Background: Mast cell tumors (MCT) are common splenic tumors in cats, but there is limited inform... more Background: Mast cell tumors (MCT) are common splenic tumors in cats, but there is limited information on treatment outcomes of cats with this disease. Materials and methods: This retrospective study evaluated treatment outcomes in 64 cats with splenic MCT. Cats were categorized into the following treatment groups: splenectomy (A, n = 20); splenectomy with chemotherapy (B, n = 20); chemotherapy alone (C, n = 15); or supportive care (D, n = 9). Results: Median tumor specific survival (MTSS) was: 856, 853, 244, 365 days for groups A, B, C, and D, respectively. The MTSS was not significantly different between the 4 groups. However, comparing cats that had splenectomy (A and B) versus those that did not (C and D), the MTSS was 856 and 342 days, respectively (p=0.008). None of the prognostic factors analyzed significantly influenced survival. Conclusion: Splenectomy (+/-chemotherapy) significantly prolongs survival in cats with mast cell tumors. The role of chemotherapy remains unknown.
Journal of Veterinary Internal Medicine, Sep 1, 2004
Cancer cachexia is a well‐recognized syndrome in human patients that is characterized by progress... more Cancer cachexia is a well‐recognized syndrome in human patients that is characterized by progressive involuntary weight loss. The prevalence of this syndrome in veterinary cancer patients is unknown. This study's objective was to investigate the occurrence of weight loss and cachexia, as characterized by body condition scoring, in dogs presented to a veterinary oncology service. Information collected on 100 dogs included signalment, diagnosis, weight at time of diagnosis, and, when available, weight from a time approximately 12 months before diagnosis. Body condition was assessed by using a 9‐point system based on body silhouette and palpation of adipose tissue (4–5 = optimal, 1 = extreme cachexia, 9 = extreme obesity). Muscle wasting was scored based on palpation of skeletal muscle (3 = no wasting, 2 = mild, 1 = moderate, 0 = severe). Only 4% of the dogs exhibited cachexia as defined by a body condition score ≤ 3, whereas 29% were classified as markedly overweight (≥7). Fifteen percent had evidence of clinically relevant muscle wasting (≤1). Body weight from a time before the diagnosis of cancer was available for 64 dogs. At the time of diagnosis, 31% had maintained or gained weight, 31% had lost up to 5%, 14% had lost between 5 and 10%, and 23% had lost >10% of body weight. Overall, the percentage of dogs with signs indicating a decline in nutritional status was less than what has been reported for human cancer patients. Future studies should investigate the extent to which weight loss occurs in canine patients on an appropriate plane of nutrition as well as to establish whether an association exists between poor nutritional status and outcome in canine cancer patients.
Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identificatio... more Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species. Feline mammary tumors (FMT) serve as models for extremely aggressive triple negative breast cancer (TNBC) in humans, with high rates of local and distant recurrence after resection. Despite the aggressive clinical behavior of most FMT, current prognostic indicators are insufficient for accurately predicting outcome, similar to human patients. Given significant heterogeneity of mammary tumors, there has been a recent focus on identification of universal tumor-permissive stromal features that can predict biologic behavior and provide therapeutic targets to improve outcome. As in human and canine patients, collagen signatures appear to play a key role in directing mammary tumor behavior in feline patients. We find that patients bearing FMTs with denser collagen, as well as longer, thicker and straighter fibers and less identifiable tumor-stromal boundaries had poorer outcomes, independent of the clinical variables grade and surgical margins. Most importantly, including the collagen parameters increased the predictive power of the clinical model. Thus, our data suggest that similarities with respect to the stromal microenvironment between species may allow this model to predict outcome and develop novel therapeutic targets within the tumor stroma that would benefit both veterinary and human patients with aggressive mammary tumors.
Indolent lymphoma comprises up to 29% of all canine lymphoma; however, limited information exists... more Indolent lymphoma comprises up to 29% of all canine lymphoma; however, limited information exists regarding the subtypes and biological behaviour. This retrospective study describes the clinical characteristics, histopathological and immunohistochemical features, treatment, outcome and prognostic factors for 75 dogs with indolent lymphoma. WHO histopathological classification and immunohistochemistry (IHC) for CD79a, CD3, Ki67 and P-glycoprotein (P-gp) was performed. The most common histopathological subtype was T-zone, 61.7%, (MST 33.5 months), followed by marginal zone, 25%, (MST 21.2 months), P = 0.542. The addition of IHC to preliminary histopathological classification resulted in a revised diagnosis in 20.4% of cases. The use of systemic treatment did not influence survival, P = 0.065. Dogs treated with chlorambucil and prednisone did not reach a MST, compared with a MST of 21.6 months with CHOP-based chemotherapy, P = 0.057. The overall MST of 4.4 years confirms that this is indeed an indolent disease. However, the effect of systemic treatment must be determined through prospective trials.
Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment; however, most ... more Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment; however, most canine reports are case series. This case-control study examined risk factors for SHC in dogs with lymphoma receiving oral cyclophosphamide. Twenty-two dogs with SHC and 66 control dogs were identified. On univariate analysis, SHC risk factors included age (P = 0.041), induction protocol (P = 0.021) and cumulative cyclophosphamide dose (P = 0.002). On multivariate analysis, increasing cumulative cyclophosphamide dose was associated with increased risk of SHC and the 'short' induction protocol (protocol 1) was associated with decreased risk. Controlling for age and induction protocol, odds of SHC increased by 2.21 per 750 mg m −2 increase in cyclophosphamide dose (P = 0.001). SHC from oral cyclophosphamide is a predominately delayed toxicity resulting from high cumulative doses.
Journal of The American Animal Hospital Association, Jul 1, 2014
Inside the Brachycephalic Nose: Conchal Regrowth and Mucosal Contact Points After Laser-Assisted ... more Inside the Brachycephalic Nose: Conchal Regrowth and Mucosal Contact Points After Laser-Assisted Turbinectomy Riccarda Schuenemann, and Gerhard Oechtering This prospective observational study analyzed conchal regrowth after laser-assisted turbinectomy (LATE) in brachycephalic dogs and the mucosal contact of regrown conchae. Eighty brachycephalic dogs (41 pugs, 39 French bulldogs [FBs]) that underwent LATE because of obstructing conchae were evaluated by endoscopy 7 days and 6 mo after surgery. At 6 mo, 96% of FBs' and 65% of pugs' nasal cavities showed regrowth of turbinates. FBs showed higher growth grades than pugs. Revision surgery because of reobstructing regrowth was required in the nasal cavities of 17% of FBs and 3% of pugs. The mean number of contact points reduced from 3.0 in FB and 1.7 in pugs before surgery to 1.2 in FB and 0.2 in pugs after conchal regrowth. Recollapse of nares after surgery significantly influenced the frequency of reoccurrence of contact points. LATE was proven to be an effective treatment of intranasal obstruction caused by mucosal contact between conchae. Conchal regrowth commonly occurs after surgical removal, but the new conchae cause less obstruction due to a significant reduction in number of contact points. Revision surgery because of reobstruction is rarely necessary. The important physiologic functions of conchae make nonobstructing regrowth desirable.
Veterinary Clinics of North America-small Animal Practice, May 1, 2003
Mammary gland tumors are common in the older female dog. Approximately 50% of mammary gland tumor... more Mammary gland tumors are common in the older female dog. Approximately 50% of mammary gland tumors are benign and the other half are malignant (most commonly carcinomas). The development of mammary gland tumors is found to be hormone dependent in dogs. Therefore, the risk for developing these tumors is greatly reduced with early spaying. Spaying after two years of age or more than three heat cycles does not reduce the risk for malignant tumors; however, the spaying of intact dogs is recommended at the time of tumor removal.
ABSTRACT Hyperspectral imaging is an emerging technology in the field of biomedical engineering w... more ABSTRACT Hyperspectral imaging is an emerging technology in the field of biomedical engineering which may be used as a noninvasive modality to characterize tumors. In this paper, a hyperspectral imaging system was used to characterize canine mammary tumors of unknown histopathology (pre-surgery) and correlate these results with the post-surgical histopathology results. The system consisted of a charge coupled device (CCD) camera, a liquid crystal tunable filter in the near infrared range (650-1100 nm) and a controller. Spectral signatures of malignant and benign canine mammary tumors were extracted and analyzed. The reflectance intensities of malignant tumor spectra were generally lower than benign tumor spectra over the entire wavelength range. Previous studies have shown that cancerous tissues have a higher hemoglobin and water content, and lower lipid concentration with respect to benign tissues. The decreased reflectance intensity observed for malignant tumors is likely due to the increased microvasculature and therefore higher blood content of malignant tissue relative to benign tissue. Peaks at 700, 840, 900 and 970 nm were observed in the second derivative absorption spectra, these peaks were attributed to deoxy-hemoglobin, oxy-hemoglobin, lipid and water respectively. A ‘Tissue Optical Index’ was developed that enhances contrast between malignant and benign canine tumors. This index is based on the ratio of the reflectance intensity values corresponding to the wavelengths associated with the four chromophores. Preliminary results from 22 canine mammary tumors showed that the sensitivity and specificity of the proposed method is 85.7% and 94.6% respectively. These results show promise in the non-invasive optical diagnosis of canine mammary cancer.
Journal of the American Animal Hospital Association, 2018
A 2 yr old male castrated golden retriever was evaluated for a rapidly progressing maxillofacial ... more A 2 yr old male castrated golden retriever was evaluated for a rapidly progressing maxillofacial spindle cell tumor. On examination, an ill-defined left maxillary mass, a 2 cm swelling under the left eye, and an enlarged left mandibular lymph node were noted. The dog was bright and alert but appeared painful upon jaw extension. Cytology from the lymph node revealed metastatic disease. Thoracic radiographs and computed tomography scan revealed pulmonary nodules. Computed tomography of the head and neck revealed a 6.7 × 4.1 × 6.5 cm mass at the rostral aspect of the left zygomatic arch invading the orbit. A second opinion of the biopsy specimen in conjunction with positive immunohistochemical staining for desmin led to a revised diagnosis of rhabdomyosarcoma. Treatment consisted of three doses of palliative radiation therapy, in 8 Gy fractions, and chemotherapy with vincristine, cyclophosphamide, and doxorubicin. A rapid clinical response was noted shortly after treatment initiation; ...
Small to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory... more Small to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory surgery with no prior history of pulmonary disease. Initial response to several chemotherapy regimens was poor, but a long-term remission was achieved with CCNU (lomustine) and corticosteroid therapy. After receiving a total cumulative CCNU dose of 552 mg m − 2 over 12 months, an acute episode of respiratory distress occurred and the cat died. Necropsy identifi ed severe diffuse pulmonary fi brosis and no signs of lymphoma. This is the fi rst report of pulmonary fi brosis following high cumulative dose nitrosourea chemotherapy in a cat.
The epithelial-mesenchymal transition (EMT) is a dynamic process linked to metastasis in many tum... more The epithelial-mesenchymal transition (EMT) is a dynamic process linked to metastasis in many tumor types, including mammary tumors. In this study, we evaluated E-cadherin and vimentin immunolocalization in primary canine mammary carcinomas (20 cases) and their respective metastases, as well as their relationship with the core regulators SNAIL/SLUG. To assess the number of cells undergoing the process of EMT, we quantitated double-positive (E-cadherin þ /vimentin þ) cells using immunofluorescence, via cell counting and image analysis. In addition, SNAIL/SLUG expression was evaluated by established immunohistochemical methods. Primary tumors had significantly more E-cadherin þ /vimentin þ co-expression than their paired respective lymph node or distant metastasis, respectively. Furthermore, the percentage of E-cadherin þ /vimentin þ cells in grade II and III carcinomas was significantly higher than in grade I tumors. Primary tumors had significantly higher SNAIL/SLUG expression when analyzed based on the percentage of positive cells compared with their respective distant metastases in pairwise comparisons. An inverse correlation was noted between SNAIL/SLUG immunoreactivity and percentage of E-cadherin þ /vimentin þ immunopositive cells in primary tumor samples when SNAIL/SLUG immunoreactivity was grouped into 2 categories (high versus low) based on percentage-positive staining. These results show a positive correlation between E-cadherin þ /vimentin þ cells and higher tumor grade, establish differences between primary tumor and their respective metastases, and provide further support that EMT plays a critical role in the metastasis of canine mammary carcinoma. Furthermore, these data suggest that modulation of this process could provide greater therapeutic control and provide support for further research to determine if E-cadherin þ /vimentin þ co-immunoreactivity imparts predictive value in the clinical outcome of patients with canine mammary carcinomas.
Journal of Feline Medicine and Surgery, Apr 1, 2009
This study examined the efficacy of doxorubicin-based chemotherapy used for rescue therapy in ref... more This study examined the efficacy of doxorubicin-based chemotherapy used for rescue therapy in refractory feline lymphoma. Records of 23 cats with lymphoma treated with chemotherapy who received doxorubicin for the first time in a rescue setting were reviewed. Seventeen (74%) of the 23 cats had only one treatment of doxorubicin. Five (22%) of the 23 cats had a positive response to doxorubicin and were given additional doses. The response to therapy in 4/5 of these responders could be assessed objectively, of which, two cats (9%) achieved partial remission (PR) and two cats (9%) achieved complete remission (CR). The two cats that achieved CR had differing response durations (6 weeks and greater than 47 months). Three of these five (60%) responders had also received concurrent other chemotherapy in addition to doxorubicin. Cell type and the use of concurrent chemotherapy were significant predictors of response. Cats with small-medium cell lymphomas (P ¼ 0.001) and cats that received concurrent chemotherapy with doxorubicin rescue (P ¼ 0.007) were more likely to respond favorably. This study suggests that doxorubicin-based chemotherapy is not an effective rescue protocol for feline lymphoma.
In spite of major advances over the past several decades in diagnosis and treatment, breast cance... more In spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived crosslinks was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.
Background: Mast cell tumors (MCT) are common splenic tumors in cats, but there is limited inform... more Background: Mast cell tumors (MCT) are common splenic tumors in cats, but there is limited information on treatment outcomes of cats with this disease. Materials and methods: This retrospective study evaluated treatment outcomes in 64 cats with splenic MCT. Cats were categorized into the following treatment groups: splenectomy (A, n = 20); splenectomy with chemotherapy (B, n = 20); chemotherapy alone (C, n = 15); or supportive care (D, n = 9). Results: Median tumor specific survival (MTSS) was: 856, 853, 244, 365 days for groups A, B, C, and D, respectively. The MTSS was not significantly different between the 4 groups. However, comparing cats that had splenectomy (A and B) versus those that did not (C and D), the MTSS was 856 and 342 days, respectively (p=0.008). None of the prognostic factors analyzed significantly influenced survival. Conclusion: Splenectomy (+/-chemotherapy) significantly prolongs survival in cats with mast cell tumors. The role of chemotherapy remains unknown.
Journal of Veterinary Internal Medicine, Sep 1, 2004
Cancer cachexia is a well‐recognized syndrome in human patients that is characterized by progress... more Cancer cachexia is a well‐recognized syndrome in human patients that is characterized by progressive involuntary weight loss. The prevalence of this syndrome in veterinary cancer patients is unknown. This study's objective was to investigate the occurrence of weight loss and cachexia, as characterized by body condition scoring, in dogs presented to a veterinary oncology service. Information collected on 100 dogs included signalment, diagnosis, weight at time of diagnosis, and, when available, weight from a time approximately 12 months before diagnosis. Body condition was assessed by using a 9‐point system based on body silhouette and palpation of adipose tissue (4–5 = optimal, 1 = extreme cachexia, 9 = extreme obesity). Muscle wasting was scored based on palpation of skeletal muscle (3 = no wasting, 2 = mild, 1 = moderate, 0 = severe). Only 4% of the dogs exhibited cachexia as defined by a body condition score ≤ 3, whereas 29% were classified as markedly overweight (≥7). Fifteen percent had evidence of clinically relevant muscle wasting (≤1). Body weight from a time before the diagnosis of cancer was available for 64 dogs. At the time of diagnosis, 31% had maintained or gained weight, 31% had lost up to 5%, 14% had lost between 5 and 10%, and 23% had lost >10% of body weight. Overall, the percentage of dogs with signs indicating a decline in nutritional status was less than what has been reported for human cancer patients. Future studies should investigate the extent to which weight loss occurs in canine patients on an appropriate plane of nutrition as well as to establish whether an association exists between poor nutritional status and outcome in canine cancer patients.
Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identificatio... more Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species. Feline mammary tumors (FMT) serve as models for extremely aggressive triple negative breast cancer (TNBC) in humans, with high rates of local and distant recurrence after resection. Despite the aggressive clinical behavior of most FMT, current prognostic indicators are insufficient for accurately predicting outcome, similar to human patients. Given significant heterogeneity of mammary tumors, there has been a recent focus on identification of universal tumor-permissive stromal features that can predict biologic behavior and provide therapeutic targets to improve outcome. As in human and canine patients, collagen signatures appear to play a key role in directing mammary tumor behavior in feline patients. We find that patients bearing FMTs with denser collagen, as well as longer, thicker and straighter fibers and less identifiable tumor-stromal boundaries had poorer outcomes, independent of the clinical variables grade and surgical margins. Most importantly, including the collagen parameters increased the predictive power of the clinical model. Thus, our data suggest that similarities with respect to the stromal microenvironment between species may allow this model to predict outcome and develop novel therapeutic targets within the tumor stroma that would benefit both veterinary and human patients with aggressive mammary tumors.
Indolent lymphoma comprises up to 29% of all canine lymphoma; however, limited information exists... more Indolent lymphoma comprises up to 29% of all canine lymphoma; however, limited information exists regarding the subtypes and biological behaviour. This retrospective study describes the clinical characteristics, histopathological and immunohistochemical features, treatment, outcome and prognostic factors for 75 dogs with indolent lymphoma. WHO histopathological classification and immunohistochemistry (IHC) for CD79a, CD3, Ki67 and P-glycoprotein (P-gp) was performed. The most common histopathological subtype was T-zone, 61.7%, (MST 33.5 months), followed by marginal zone, 25%, (MST 21.2 months), P = 0.542. The addition of IHC to preliminary histopathological classification resulted in a revised diagnosis in 20.4% of cases. The use of systemic treatment did not influence survival, P = 0.065. Dogs treated with chlorambucil and prednisone did not reach a MST, compared with a MST of 21.6 months with CHOP-based chemotherapy, P = 0.057. The overall MST of 4.4 years confirms that this is indeed an indolent disease. However, the effect of systemic treatment must be determined through prospective trials.
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Papers by Karin Sorenmo