Biomedical subjects

Barbara E Kitchell

Publications and source records attributed to Barbara E Kitchell.

12 recordsLinked to original sources

PubMed2005

Isolation, characterization, and expression of stromelysin-1 in primary tumors of dogs.

OBJECTIVE: To isolate and characterize the cDNA sequence of canine stromelysin-1 (matrix metalloproteinase [MMPI-3), screen various naturally developing primary tumors of dogs, and assess the effect of stromelysin-1 on survival of dogs with cancer. SAMPLE POPULATION: 3 canine cell lines and biopsy specimens of primary tumors collected from 54 dogs. PROCEDURE: 3 canine cell lines and biopsy specimens of primary tumors collected from 54 dogs at the University of Illinois Veterinary Teaching Hospital were used in the study. Primer sets based on human stromelysin-1 and consensus sequences were designed for expression, screening, and isolation. Two additional primer sets were designed for screening. Samples were assayed at least in duplicate. Data were analyzed for differences in expression of stromelysin-1 on the basis of sex, age, metastasis, malignant versus nonmalignant tissue origin, and duration of patient survival. RESULTS: A 1,479-bp cDNA nucleotide sequence was amplified from established canine cell lines. The open reading frame encoded a protein consisting of 478 amino acids. This sequence was 70% to 88% homologous with stromelysin-1 of other species at the amino acid level. Fifty-four samples were screened for stromelysin-1. Of these, 34 (63%) had positive results and 20 (37%) had negative results for expression. Stromelysin-1 and metastasis were associated with a poor prognosis for survival. CONCLUSIONS AND CLINICAL RELEVANCE: Stromelysin-1 is a potential activator of other members of the MMP family. Additional studies are needed to investigate the relationship between stromelysin-1 production and aggressive biological behavior of tumors in dogs.

Amino Acid Sequence↗

PubMed2004

Isolation, characterization, and expression of feline stromelysin-1 in naturally developing tumors in cats.

OBJECTIVE: To detect, isolate, and characterize feline stromelysin-1 (ie, matrix metalloproteinase [MMP]-3) in naturally developing tumors in cats. SAMPLE POPULATION: 31 tissue samples obtained from primary tumors and 6 samples of normal tissues from cats. PROCEDURE: Biopsy specimens were obtained from primary tumors. Primers were designed on the basis of known sequences. The sequence of stromelysin-1 was cloned and analyzed. An additional primer set was used as a screening tool. Samples were assayed in duplicate or triplicate, when possible. Data obtained were analyzed for differences in expression of stromelysin-1 with regard to overall survival among cats of various sex, age, and disease status. RESULTS: A 1,181-bp cDNA nucleotide sequence was amplified. The open reading frame encoded 393 amino acids. This amino acid sequence shared 70% to 85% sequence homology with sequences of other species. In addition, samples were screened for stromelysin-1. Of the 31 tumor samples tested, 16 (51.6%) had positive results for expression of stromelysin-1. Total RNA expression was detected in a diverse group of tumor types. Prognostic factors associated with a shorter duration of survival included evidence of metastasis and metastasis associated with expression of stromelysin-1. CONCLUSIONS AND CLINICAL RELEVANCE: Feline stromelysin-1 contains all the conserved regions typically found in members of the MMP family. Activity of stromelysin-1 has been implicated in a wide number of physiologic and pathologic processes. Identification of this gene may lead to the development of useful reagents to assist with diagnosis and management of neoplastic diseases in cats.

Amino Acid Sequence↗

PubMed2004

Expression of matrix metalloproteinases in feline vaccine site-associated sarcomas.

OBJECTIVES: To screen for expression of 9 predominant members of the matrix metalloproteinase (MMP) family, including membrane-type matrix metalloproteinases (MT-MMPs) and tissue inhibitors of metalloproteinases (TIMPs), in primary tumor tissue biopsy specimens of vaccine site-associated sarcomas (VSS) in cats and compare expression profiles of VSS with expression profiles of non-VSS and carcinomas. SAMPLE POPULATION: 31 primary tumor tissue biopsy specimens and 6 nontumor (normal) tissue biopsy specimens. PROCEDURES: Tissue specimens were obtained from primary tumor biopsy specimens of cats. Primers for reverse transcriptase-polymerase chain reaction assay were designed on the basis of known sequences. Data were analyzed for patterns of expression of MMPs, MT-MMPs, and TIMPs. Differences in expression patterns were evaluated among cats of differing genders, ages, metastasis status, and overall survival durations, and between cats with VSS and cats with non-VSS tumor types. RESULTS: A total of 31 primary tumor tissue biopsy specimens and 6 nontumor (normal) tissue biopsy specimens were screened for the presence of 6 MMPs and 3 TIMPs. Matrix metalloproteinase and TIMP expression was found in non-VSS, carcinomas, and VSS. No significant differences were found in patterns of expression among tumor types. Metastasis was found to be the only predictive factor for overall survival duration. A significant correlation was found between MMP2 and MT-MMP16 expression and overall duration of survival. CONCLUSIONS AND CLINICAL RELEVANCE: The identification of MMPs in feline VSS supports an underlying inflammatory pathogenesis for this tumor. Expression of MMP2 and MT-MMP16 were correlated with survival time in our study.

Analysis of Variance↗

PubMed2003

Primary extraskeletal hepatic osteosarcoma in a cat.

A 13-year-old spayed female domestic shorthair cat with an abdominal mass was evaluated; radiography revealed a radiopaque mass in the cranioventral region of the abdomen. A celiotomy was performed, and the mass was identified histologically as a hepatic osteosarcoma. Complete remission of the tumor was accomplished after partial hepatectomy and adjuvant treatment with carboplatin.

Animals↗

PubMed2003

New chemotherapy agents in veterinary medicine.

Several anticancer drugs have been added to the therapeutic armamentarium in recent years. Some of these agents are traditional drugs with a long history of use in human oncology. Increased sophistication in clinical trial design in veterinary oncology has allowed the incorporation of agents previously viewed as excessively toxic. Other agents have been developed more recently. This article summarizes the veterinary experience with two older alkylating agents, lomustine and streptozocin, and newer compounds ifosfamide and gemcitabine. The published literature regarding veterinary use of these agents is limited, and the reader is advised to contact a veterinary oncologist for current guidelines when contemplating use of these agents.

Animals↗

PubMed2003

The biology of melanocytes.

In veterinary medicine, our understanding of the biology and regulation of melanocytic function is mostly based on information realized from human and murine studies. Improved understanding of the biology of melanocytes is needed to develop more effective treatment regimens for malignant melanoma and other melanocytic disorders. In vertebrates, melanocytes are well known for their role in skin pigmentation, hair and feather coloration, and for their ability to produce and distribute melanin to surrounding keratinocytes. Enzymes involved in melanin synthesis are present exclusively in melanosomes. The type of melanin synthesized by melanocytes in mammals is regulated at a genetic, biochemical and environmental level. These regulatory factors affect not only the phenotypic appearance, but also the photoprotective properties of melanin. This review addresses the biology of melanocytes, melanin synthesis and the photoprotective properties of melanin.

Animals↗

PubMed2003

Identification of Haemobartonella felis (Mycoplasma haemofelis) in captive nondomestic cats.

This study was undertaken to determine whether Haemobartonella felis (Mycoplasma haemofelis), the causative bacterial agent of feline infectious anemia, infects nondomestic cats. Routine complete blood count and polymerase chain reaction (PCR) were performed to detect the gene for 16S ribosomal RNA for the organism. Sixty-four blood samples were collected from 54 nondomestic cats, including tigers (Panthera tigris), cheetahs (Acinonyx jubatus), lions (P. leo), mountain lions (Felis concolor), snow leopards (P. unica), and a jaguar (P. onca). Some cats were sampled on two or three different dates. Two tigers were positive for H. felis by PCR analysis. As previously described in domestic cats, the parasitemia appears to be intermittent in nondomestic cats.

Anemia↗

PubMedDate not supplied

Cobalt radiation with or without low-dose cisplatin for treatment of canine naso-sinus carcinomas.

The objective of this study was to determine if low-dose cisplatin could be added safely to radiation therapy for the treatment of naso-sinus carcinomas in dogs. Thirty-one dogs were evaluated; 18 of these dogs received cobalt radiation in combination with low-dose cisplatin while 13 dogs received radiation alone. No difference was observed for acute or late radiation effects. Cisplatin was administered at a dosage of 7.5 mg/m2 20 min prior to every other radiation treatment. An initial dose of 10 mg/m2 was intended but toxicity (primarily azotemia) was unacceptable. Cisplatin was administered as prescribed in 12 of 18 dogs. Cisplatin was discontinued in 2 dogs because of azotemia. In the other 4 dogs cisplatin was not administered as prescribed because the dogs were withdrawn from treatment due to disease progression or radiation effects. There was no long-term renal disease in patients who developed azotemia. The overall median survival was 433 days with 4 (12.9%) dogs still alive at the completion of the study.

Animals↗

PubMedDate not supplied

The basic biology of malignant melanoma: molecular mechanisms of disease progression and comparative aspects.

Malignant melanoma (MM) is a life-threatening disease characterized by a highly aggressive biologic behavior in both humans and dogs. Despite improvements in diagnosis and patient care, most deaths from MM are due to metastases that are resistant to conventional treatment modalities. To ultimately reduce the mortality associated with metastatic disease, it is necessary to better define the fundamental molecular mechanisms of malignant tumor progression. The progression of disease is a consequence of the complex interactions between malignantly transformed cells and host factors. Characterization of the stages of tumor progression and the changes occurring in highly malignant cells is important for the development of effective treatment regimens. The dys-regulated molecular mechanisms of transformed melanocytes are presently being characterized. In this review, we summarize the current understanding of the molecular phases in the progression of MM, which include genetic instability, dysregulated proliferation of melanocytes, increased invasion and metastasis, and angiogenesis.

Animals↗

PubMedDate not supplied

Hematological toxicity and therapeutic efficacy of lomustine in 20 tumor-bearing cats: critical assessment of a practical dosing regimen.

Twenty cats with spontaneously arising tumors received oral lomustine at a dose range of 32 to 59 mg/m2 every 21 days. Due to biohazard concerns associated with lomustine capsule reformulation, a standardized 10-mg capsule dosage was used for all cats regardless of body weight. Severe hematological toxicity was infrequent, with the incidence of either grade III or IV neutropenia and thrombocytopenia being 4.1% and 1.0%, respectively. Cats receiving higher cumulative doses of lomustine trended toward a greater likelihood for progressive neutropenia (P=0.07). Two cats with lymphoma, two cats with fibrosarcoma, and one cat with multiple myeloma achieved a measurable partial response to lomustine therapy. Cats treated with higher dosages of lomustine trended toward statistically significant higher response rates (P=0.07).

Administration, Oral↗

PubMedDate not supplied

Chlorambucil-induced myoclonus in a cat with lymphoma.

Chlorambucil is an alkylating agent commonly used in veterinary oncology for conditions including lymphoma. Chlorambucil neurotoxicity has been well recognized in human patients. Onsets of central nervous system signs, such as myoclonus, tremors, muscular twitching, agitation, and tonic-clonic seizures, have been reported in humans and laboratory animals treated with chlorambucil. This case of a cat with intestinal lymphoma represents the first veterinary patient reported to have chlorambucil-induced neurotoxicity. Neurotoxicity should be considered a potential side effect of chlorambucil therapy in veterinary patients.

Animals↗

PubMedDate not supplied

Gemcitabine as a radiosensitizer for nonresectable feline oral squamous cell carcinoma.

Eight cats with locally advanced, oral squamous cell carcinoma (SCC) were treated with a combination of gemcitabine and palliative radiotherapy. Low-dose gemcitabine was administered twice weekly (25 mg/m2) in conjunction with megavoltage radiation in 6 Gray (Gy) fractions for a total dose of 36 Gy. Responses included two complete and four partial responses, and two cats had no response to therapy. Median duration of remission was 42.5 days (range, 11 to 85 days). Median survival time was 111.5 days (range, 11 to 234 days). This data suggests that a combination of low-dose gemcitabine and palliative radiation therapy may be tolerable for cats with oral SCC and may cause a therapeutic benefit.

Animals↗