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Biomedical subjects

R C Rosenthal

Publications and source records attributed to R C Rosenthal.

At least 19 recordsLinked to original sources

Spontaneous regression of osteosarcoma in four dogs.

Spontaneous regression of primary malignant bone tumors is rare but has been reported in the human literature. To the authors' knowledge, spontaneous regression of primary bone tumors in dogs or cats has not been reported. Osteosarcoma (OSA) is the most common primary bone tumor in humans, and it has been reported that the incidence of OSA is 40 to 50 times greater in dogs than humans. In this report, high-grade OSA was diagnosed in biopsy specimens obtained from 4 dogs that subsequently underwent spontaneous regression without tumor-specific treatment. Osteosarcoma in dogs has characteristics similar to that of OSA in humans.

Animals↗

Use of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II), a liposomal cisplatin analogue, in cats with oral squamous cell carcinoma.

OBJECTIVE: To determine clinical response and toxic effects of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP) administered i.v. at escalating doses to cats with oral squamous cell carcinoma (SCC). ANIMALS: 18 cats with oral SCC. PROCEDURE: Cats that failed to respond to conventional treatment or had nonresectable tumors were included. Data included a CBC, serum biochemical analyses, urinalysis, cytologic examination of a fine-needle aspirate of enlarged lymph nodes, and thoracic and oral radiographs for clinical staging. A starting dose (75 to 100 mg/m2 of L-NDDP) was administered i.v.. At 21-day intervals, subsequent doses increased by the rate of 5 or 10 mg/m2. Response was evaluated every 21 days by tumor measurement and thoracic radiography. Quality of life was assessed by owners, using a performance status questionnaire. RESULTS: On average, cats received 2 treatments. Toxicoses included an intermittent, acute anaphylactoid-parasympathomimetic reaction, lethargy or sedation (< or = 24 hours), inappetence or signs of depression (< or = 72 hours), mild to moderate increase in hepatic enzyme activity, and melena. Pulmonary, renal, or hematopoietic abnormalities were not evident. Performance status surveys indicated normal behavior and grooming or decreased activity and self-care (19/20 assessments), ate well with or without assistance (15/20), and did not lose weight (15/20). Median survival time was 59.8 days (mean, 54.1 days). CONCLUSIONS AND CLINICAL RELEVANCE: L-NDDP was ineffective for treatment of cats with oral SCC. None of the cats had a complete or partial remission. Acute toxicoses and poor therapeutic response limit therapeutic usefulness of L-NDDP in cats, unless dosage, frequency, and administration procedures can be improved.

Animals↗

Adjuvant therapy for melanoma in dogs: results of randomized clinical trials using surgery, liposome-encapsulated muramyl tripeptide, and granulocyte macrophage colony-stimulating factor.

Spontaneous canine oral melanoma (COM) is a highly metastatic cancer, resistant to chemotherapy, and can serve as a model for cancer immunotherapy. Liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) can activate the tumoricidal activity of the monocyte-macrophage system following i.v. injection. The objective of these studies was to evaluate the therapeutic effectiveness of L-MTP-PE administered alone and combined with recombinant canine granulocyte macrophage colony-stimulating factor (rcGM-CSF) in dogs undergoing surgery for oral melanoma. Ninety-eight dogs with histologically confirmed, clinically staged, oral melanoma were entered into two randomized, double-blind, surgical adjuvant trials. In trial 1, 50 dogs were stratified based on clinical stage and randomized to once a week L-MTP-PE or lipid equivalent (control). When all of the clinical stages were combined, no difference in disease-free survival or in survival time (ST) were detected. However, within stage I, dogs receiving L-MTP-PE had a significant increase in ST compared with control, with 80% of the dogs treated with L-MTP-PE still alive at >2 years. Within each stage II and stage III, there was no difference detected between the treatment groups. In trial 2, 48 dogs were stratified on the basis of clinical stage and extent of surgery (simple resection or radical excision), treated with L-MTP-PE two times a week, and randomized to rcGM-CSF or saline (placebo) given s.c. daily for 9 weeks. Within each stage and when all of the stages were combined, there was no difference between the treatment groups. In both studies, stage I COM is associated with a better prognosis. No effect on survival was observed with regard to tumor location in the oral cavity, sex, type/extent of surgery, or age. In a subset of dogs tested, pulmonary alveolar macrophage cytotoxicity was enhanced with combined rcGM-CSF and L-MTP-PE but not in dogs treated with L-MTP-PE alone. The present study indicates that after surgery, L-MTP-PE administered alone or combined with rcGM-CSF showed no significant antitumor activity in treating advanced stage COM. In early stage COM, L-MTP-PE was shown to result in a prolongation of ST. Furthermore, this study provides additional rationale for the use of the dog model for human malignant melanoma.

Acetylmuramyl-Alanyl-Isoglutamine↗

Multimodality therapy: using the best available treatments together rationally.

Cancer cases comprise an increasingly important part of companion animal practice. As the state of veterinary oncology continues to improve, the combined use of modalities (surgery, chemotherapy, and radiotherapy for the most part, biologic response modification to some extent) will be widely evaluated, and its clinical application will become more common.

Animals↗

Lymphoma in dogs: chemotherapy.

This article reviews important findings regarding chemotherapeutic management of previously untreated lymphoma in dogs. It emphasizes publications in the past few years and discusses the possible use of short-term, rather than long-term, protocols for this disease.

Animals↗

Hematological effects of radiant heat-induced whole body hyperthermia on dogs.

The effects on hematological parameters of radiant heat-induced whole body hyperthermia (WBH) at 40.5 degrees C and 41.8 degrees C were determined in 6 normal dogs. Complete blood counts determined prior to WBH, immediately post WBH plateau, and at 1, 2, 7, and 14 days posttreatment did not change significantly following WBH at 40.5 degrees C or 41.8 degrees C. Similarly, no significant changes were detected in platelet counts measured following 40.5 degrees C WBH. In contrast, platelet counts 11 days following 41.8 degrees C WBH increased significantly (P < 0.05) consistent with the hypothesis of induction of putative WBH-induced platelet stimulating factors.

Animals↗

Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin.

Two randomized, double-blind clinical trials in dogs with spontaneous appendicular osteosarcoma treated with combination chemoimmunotherapy are reported. In both trials, dogs without overt metastasis underwent complete amputation of the affected limb. In trial 1, 40 dogs were treated with cisplatin chemotherapy [(CDDP), 70 mg/m2 i.v. every 28 days x 4]. Following CDDP, dogs without evidence of overt metastasis (n = 25) were randomized to receive liposome-encapsulated muramyl tripeptide phosphatidylethanolamine ](L-MTP-PE), 2 mg/m2 i.v.) or placebo liposomes (lipid equivalent) twice weekly for 8 weeks. Of 14 dogs in the placebo group, 13 (93%) died of metastasis; the median survival time was 9.8 months. Of 11 dogs in the L-MTP-PE group, 8 (73%) developed metastasis; the median survival time was 14.4 months, which was significantly longer than that of the placebo group (P < 0.01). In trial 2, 64 dogs received CDDP (70 mg/m2 i.v. every 21 days x 4) and were randomized to concurrently receive L-MTP-PE (2 mg/m2 i.v.) twice or once weekly, or placebo liposomes once weekly for 8 weeks. Median survival times were 10.3, 10.5, and 7.6 months, respectively. There were no significant differences among the three treatment groups in trial 2. Survival times for dogs receiving L-MTP-PE in trial 1 were significantly longer than those for dogs in trial 2 that received four doses of CDDP concurrently with twice weekly L-MTP-PE (P < 0. 04). The results of the first trial confirm our previous observation that L-MTP-PE has antimetastatic activity in dogs with osteosarcoma when given following amputation. The results of the second trial demonstrate that there is no survival advantage of administering L-MTP-PE concurrently with CDDP.

Acetylmuramyl-Alanyl-Isoglutamine↗

Current studies of liposome muramyl tripeptide (CGP 19835A lipid) therapy for metastasis in spontaneous tumors: a progress review.

Targeted delivery of macrophage activating agents is an attractive approach to treat micrometastatic disease. Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a potent activator of monocytes/macrophages in humans, mice, and dogs. We have conducted clinical trials in dogs with malignant and highly metastatic spontaneous tumors. Presented are results of our trials evaluating L-MTP-PE in combination with surgery and chemotherapy in dogs with spontaneous osteosarcoma and hemangiosarcoma, particularly relevant malignancies having having many similarities to human cancer. Osteosarcoma dogs received chemotherapy following surgery (cisplatin q 28 days x 4). At completion of chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p < 0.021). Dogs with splenic hemangiosarcoma received combination chemotherapy following surgery (doxorubicin and cyclophosphamide q 21 days x 4). At the first chemotherapy, dogs were randomized to receive L-MTP-PE or placebo. The L-MTP-PE group had a significantly longer median survival time compared to the placebo group (p < 0.03). These studies show that L-MTP-PE is an effective agent for treatment of metastasis and can be safely administered in combination with chemotherapy.

Acetylmuramyl-Alanyl-Isoglutamine↗

Preclinical evaluation of L-asparaginase and methotrexate administered at intermediate doses in dogs.

The role of L-asparaginase (L-ASP) in limiting signs of methotrexate (MTX) toxicosis was studied. Eight dogs were randomly allotted to 2 groups of 4 dogs. All dogs were given 400 IU of L-ASP/kg of body weight IM, on day 1. On day 10, group-1 dogs were given 3 mg of MTX/kg, IV, and group-2 dogs were given 6 mg of MTX/kg, IV. All dogs were given 400 IU of L-ASP/kg, IM, 24 hours later (on day 11). One group-2 dog was euthanatized on day 16 because of severe gastrointestinal signs that were unresponsive to treatment. A second dose of MTX, identical to that given on day 10, was given on day 20 to each surviving dog, followed by L-ASP on day 21. On day 67, the 7 surviving dogs were given 3 mg of MTX/kg, IV. Adverse reactions observed were vomiting, diarrhea, and weight loss. Gastrointestinal side effects of MTX were not attenuated with L-ASP and would be a serious limitation to use of MTX administered at an intermediate dose in the treatment of lymphoma in dogs.

Animals↗

The treatment of multicentric canine lymphoma.

Canine LSA is a fatal disease if untreated, but fortunately it is also a disease that is very responsive to therapeutic intervention. It is likely that most cases seen and treated by practitioners will be managed with the currently effective drugs and with new protocols as they are developed. Other approaches, including immunotherapy and BMT, are likely to remain more in the arena of the academic institution but should be available in the referral setting for appropriate cases. Great strides have been made in the less than 30 years that canine LSA has been widely treated; it is reasonable that similar progress is to be expected in the years to come.

Animals↗

Clinical approach to tumors of the skin and subcutaneous tissues.

With skin tumors, "a lump is only a lump" until a definitive diagnosis has been made. It is nearly impossible to make an accurate diagnosis solely on clinical signs. In some instances, fine-needle aspirate may be diagnostic; however, in all instances biopsy is the preferred method for definitively diagnosing canine and feline skin tumors. Prognosis and treatment depend on the diagnosis.

Animals↗

Therapy for osteosarcoma in dogs with intravenous injection of liposome-encapsulated muramyl tripeptide.

Canine osteosarcoma is a spontaneous malignancy in dogs, characterized by micrometastasis to pulmonary and extrapulmonary tissues at the time of diagnosis. Standard treatment involves amputation of the affected leg, but median survival time is 3-4 months with death due to metastasis. A randomized double-blind trial was conducted to evaluate liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (liposome/MTP-PE) as a treatment for metastasis in dogs undergoing amputation for osteosarcoma. Fourteen dogs were treated with liposome/MTP-PE, and 13 were treated with empty liposomes. Median survival time was 222 days for dogs treated with liposome/MTP-PE, compared to 77 days for dogs treated with empty liposomes (P less than .002). In the liposome/MTP-PE-treated group there were still four dogs alive and free of metastasis at greater than 1 year post surgery. Treatment was well tolerated; no significant toxic effects were noted except for mild elevations in body temperature (1-2 degrees C) for 2-6 hours post injection.

Acetylmuramyl-Alanyl-Isoglutamine↗

The impact of pharmacokinetics on cancer chemotherapy.

The benefits of pharmacokinetics can be considered from two points of view, the impact on the average patient and that on the individual patient. For the average patient, pharmacokinetic studies answer basic questions about dose, schedule, and route of administration. For the individual patient, benefits are derived from the ability of pharmacokinetic studies to define parameters of toxicity and suggest possible dose modifications.

Animals↗

Clinical and pathologic features of thyroid tumors in 26 dogs.

Thyroid tumors were diagnosed in 26 dogs between 1977 and 1984. A total of 23 of the 26 tumors were carcinomas, and 3, detected as incidental findings at necropsy, were adenomas. The median patient age was 9.5 years. Dogs of the Beagle breed were affected most commonly (5 dogs). The most common physical abnormalities in carcinoma patients were cervical swelling, dyspnea, and coughing. A total of 25 of 26 dogs were clinically euthyroid. Aspiration cytology provided diagnostic information in 8 of 17 cases. In dogs with thyroid carcinoma, a cervical soft tissue lesion was identified consistently by use of radiography and scintigraphy with sodium pertechnetate. Pulmonary metastases were detected radiographically in 8 of 21 dogs with thyroid carcinoma. Thoracic nuclear imaging confirmed the radiographic findings in 11 of 14 dogs. Surgical excision of the thyroid mass was the primary treatment for 17 dogs with carcinoma. Eight dogs died within 2 years (median, 7 months) of surgery because of primary tumor regrowth or metastases. Four dogs were alive at a range of 3 to 48 months after surgery, and 4 dogs died from unrelated causes. Necropsy of 7 dogs with thyroid carcinoma revealed neoplastic infiltration of the cervical blood vessels and pulmonary metastases in each dog. The most common histologic patterns of thyroid carcinoma were solid or compact cellular (11 dogs) and mixed solid-follicular tumors (8 dogs). Dogs with a solid carcinoma had a median survival time of 10.5 months (6 dogs), and dogs with a mixed solid-follicular tumor had a median survival time of 8 months (3 dogs).

Adenoma↗