Biomedical subjects

S J Withrow

Publications and source records attributed to S J Withrow.

143 records · Page 8Linked to original sources

PubMedDate not supplied

Identification of matrix metalloproteinases in canine cutaneous mast cell tumors.

Presence of matrix metalloproteinases has been associated with tumor invasion and metastasis in human neoplasia. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 was determined in canine mast cell tumor tissue and normal stromal tissue from 24 dogs with spontaneously occurring cutaneous mast cell tumors. Seventeen of the mast cell tumors were of histologic grade 2, and 7 were of histologic grade 3. Gelatin zymography and computer assisted densitometry image analysis were used to quantify matrix metalloproteinase concentration. Bands from canine tissues migrated in the same location as human proenzyme and active enzyme matrix metalloproteinase 2 and matrix metalloproteinase 9 standards. A semiquantitative value for each patient sample was obtained by comparing the optical assessment density of each unknown band to the optical density of the human standard. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 in histologic grade 2 mast cell tumors and histologic grade 3 mast cell tumors was compared, as was presence of matrix metalloproteinases in tumor and stromal tissue. There was dramatically more proenzyme matrix metalloproteinase 9 activity in histologic grade 3 mast cell tumors when compared to grade 2 tumors (P = .03). There was also dramatically more active enzyme matrix metalloproteinase 2 and active enzyme matrix metalloproteinase 9 activity in tumor tissue compared to stromal tissue (P = .02, P < .0001). This study demonstrates that the proenzyme and active enzyme forms of matrix metalloproteinase 2 and matrix metalloproteinase 9 are present in canine mast cell tumors. This appears to be related to the degree of histologic malignancy, although histologic grade 1 tumors were not evaluated.

Animals↗

PubMedDate not supplied

Phase I study of melphalan alone and melphalan plus whole body hyperthermia in dogs with malignant melanoma.

The maximum tolerated dose of melphalan combined with whole body hyperthermia (WBH) in dogs with spontaneous malignant melanoma was lower than in dogs not receiving WBH by a factor of 1.9 +/- 0.71. Thirty-three dogs were treated monthly with escalating doses of melphalan and followed weekly for toxicity and, when possible, tumour response. Toxicity was manifested as myelosuppression with nadir neutrophil and platelet counts occurring at 7-10 days post-treatment. The TD50 (+/- S.E.), defined by logistic regression analysis, was 0.63 (+/- 0.07) mg/kg and 0.33 (+/- 0.10) mg/kg for melphalan alone and combined with WBH, respectively. Objective tumour response in this limited series occurred in three of fourteen evaluable dogs (three of eleven treated with melphalan alone and none of three treated with WBH plus melphalan). It is concluded that melphalan combined with WBH can be safely administered, although a reduction in dose is necessary. A randomized clinical trial is required to investigate the possibility of achieving therapeutic benefit from combined melphalan and WBH.

Animals↗

PubMedDate not supplied

Phase III evaluation of doxorubicin and whole-body hyperthermia in dogs with lymphoma.

Sixty-one dogs with histologically confirmed, untreated, high-grade lymphoma were evaluated and treated with doxorubicin (DOX, 30 mg/m2) alone. Forty-seven dogs (77%) achieved a complete response. Forty-six of the 47 dogs were randomized to receive five additional treatments with doxorubicin +/- whole-body hyperthermia (WBH). Median disease-free survival for the group treated with DOX alone (n = 22) was 189 days and for the DOX plus WBH (n = 24) was 239 days (p = 0.17). After the analysis was adjusted for stratification variables (i.e. institution, weight, stage), the effect of heat on disease-free survival remained statistically insignificant (p = 0.10), but suggested a tendency towards increased disease-free survival in hyperthermic dogs. Intact male dogs had significantly shorter disease-free survival than neutered males and neutered females (178 days vs 266 days, respectively; p = 0.013). No intact females were treated. Body weight, when evaluated as a continuous variable, was found to be a negative prognostic factor (p = 0.036). Tumour volume, stage and institution were not significant. Clinical incidence of cardiac dysfunction was not increased in dogs receiving DOX and WBH; however, post-mortem histological analysis of cardiac tissue suggested that the combined therapy of DOX and WBH was associated with greater myocyte degeneration (p = 0.012) and a tendency for increased cardiac fibrosis (p = 0.08). We concluded that continued refinement of DOX-WBH protocols is warranted, and may ultimately result in significant therapeutic improvement.

Animals↗

PubMedDate not supplied

Response of canine soft tissue sarcomas to radiation or radiation plus hyperthermia: a randomized phase II study.

Sixty-four dogs with spontaneous soft tissue sarcomas without evidence of metastases were stratified by tumour volume and randomized to receive graded doses of radiotherapy (XRT) alone or radiotherapy plus hyperthermia (HT). An improvement in duration of local control was achieved with the addition of hyperthermia as compared with XRT alone (Wilcoxon, p = 0.040; log rank, p = 0.064). Overall frequency of late complications was not different for the two treatment arms when comparing across equivalent XRT dose groups. Frequency of distant metastases after therapy completion was not significantly different for the two treatment arms at 1 year (7.4% for XRT versus 20% for HT plus XRT) or 2 years (11.5% for XRT versus 25% for HT plus XRT) post therapy. These results suggest that a therapeutic gain was achieved for this group of tumour-bearing animals. Uni- and multivariate analyses were performed to examine the potential for various factors to influence treatment outcome. Patient related variables included tumour stage, histologic subtype and grade and tumour site. Treatment related variables included total radiation dose and 15 descriptors of temperature distributions achieved during hyperthermia. When considering patient related factors, tumour histology, grade and location were important predictors of time to minimum volume, but only tumour location influenced time to tumour regrowth. When considering treatment related factors, radiation dose was not significantly correlated with time to minimum volume or time to local regrowth, but it was correlated with probability for late normal tissue damage in the XRT alone group (p = 0.005). For the hyperthermia treatments, 13 of 15 tumour temperature distribution descriptors were correlated with time to minimum volume, but none were correlated with time to local regrowth. These results suggest that caution should be used in interpreting the value of temperature distribution descriptors in predicting for long-term local control after hyperthermia and radiotherapy, based on analysis of short-term responses.

Animals↗

PubMedDate not supplied

Primary rib tumors in 54 dogs.

Fifty-four dogs with primary tumors of the rib were evaluated. Thirty-four dogs had osteosarcomas, 15 dogs had chondrosarcomas, three dogs had hemangiosarcomas, and two dogs had fibrosarcomas. Forty-nine dogs had en bloc excision. Within the osteosarcoma group, nine animals received postoperative adjuvant chemotherapy. These animals had significantly longer median disease-free intervals (225 days) and median survival times (240 days) than dogs with osteosarcoma treated by surgery alone (median disease-free interval, 60 days; median survival, 90 days). Chondrosarcoma had a better prognosis (median disease-free interval, 1,080 days; median survival, 1,080 days) than osteosarcoma, hemangiosarcoma, or fibrosarcoma of the rib. Age, weight, sex, number of ribs resected, tumor volume, and total cisplatin dose did not influence survival nor disease-free interval.

Animals↗

PubMedDate not supplied

Primary osteosarcoma distal to the antebrachiocarpal and tarsocrural joints in nine dogs (1980-1992).

The medical records of nine dogs with primary osteosarcoma distal to the antebrachiocarpal or tarsocrural joint were reviewed. Eight of the nine dogs were treated with surgical removal of the primary tumor; seven received adjuvant chemotherapy; and one dog was treated with chemotherapy alone. Median survival of dogs in this series was 466 days. Six of the nine dogs died of causes attributable to osteosarcoma, and both skeletal and pulmonary metastases occurred. Survival of dogs with osteosarcoma distal to the antebrachiocarpal or tarsocrural joint was somewhat longer than survival of dogs with osteosarcoma of more common appendicular sites. However, these are aggressive tumors with a high potential for metastasis.

Animals↗

PubMedDate not supplied

Adenomatous polyps and carcinoma in situ of the canine colon and rectum: 34 cases (1982-1994).

The medical records of 34 dogs (median age, eight years) with colorectal mucosal lesions were reviewed. Hematochezia was the most common (82%) presenting sign. Most dogs (79%) presented with solitary masses located in the rectum. After histological review, 12 masses were classified as adenomatous polyps and 22 as carcinoma in situ. Recurrence of clinical signs were common (41%), and malignant transformation of the tumor was documented in 18% of the cases. A higher recurrence rate and malignant transformation occurred in dogs presented with multiple masses or diffuse disease and in dogs initially diagnosed with carcinoma in situ.

Adenoma↗

PubMedDate not supplied

Feline cutaneous squamous cell carcinoma of the nasal planum and the pinnae: 61 cases.

Cutaneous squamous cell carcinoma is a common tumor in cats and frequently occurs on the nasal planum and the pinnae. The medical records of 61 cats were reviewed for this retrospective study. Typical presentation was an older (median age, 12 years) cat with an erythematous, crusty, and erosive lesion. Methods of treatment included surgery, radiation, and cryotherapy. Disease-free interval and survival time were calculated for each case and grouped according to lesion location and treatment type. All treatments were found to be effective, with surgery resulting in the longest disease-free interval (median, 594 days).

Animals↗

PubMedDate not supplied

Digital pad transposition for replacement of the metacarpal or metatarsal pad in dogs.

A technique for digital pad transposition is described and illustrated. This technique has application for use in cases of metacarpal or metatarsal pad neoplasia or severe trauma. The transposed digital pad will provide a weight-bearing surface of heavy, keratinized epidermis in cases where the normal metacarpal or metatarsal footpad has been removed. The use of the technique in four clinical cases of footpad neoplasia also is reported.

Animals↗

PubMedDate not supplied

Multilobular osteochondrosarcoma in 39 dogs: 1979-1993.

Thirty-nine, older, large-breed dogs with multilobular osteochondrosarcoma (MLO) each presented primarily with a fixed mass involving the flat bones of the skull. Twenty-five dogs were treated with surgical resection alone, nine were treated with adjuvant therapy, and five were not treated. Forty-seven percent of dogs treated had local tumor recurrence, and 56% had metastasis. Median time to recurrence, median time to metastasis, and median survival time were 797, 542, and 797 days, respectively. Histological grade, surgical margins, and tumor location affected outcome. Long-term remission can be obtained with aggressive treatment of MLO, although it is locally invasive and moderately metastatic.

Animals↗

PubMedDate not supplied

Intermuscular lipomas of the thigh region in dogs: 11 cases.

Ten dogs with intermuscular lipomas in the thigh region were treated by surgical resection. The masses were located predominantly between the semitendinosus and semimembranosus muscles and involved the full length of the femur. These lipomas were not infiltrative but located deep between the fascial planes of the associated muscles. These tumors can appear similar to soft-tissue sarcomas in this location, but they can be differentiated by cytology and histology. Differentiation from an infiltrative lipoma is predominantly determined at the time of surgery. No tumors recurred in the median follow-up period of 17 months.

Animals↗

PubMedDate not supplied

Outcome following treatment of vertebral tumors in 20 dogs (1986-1995).

Twenty dogs with histopathologically confirmed primary (n=15) or metastatic (n=5) osteosarcoma (n=14) or fibrosarcoma (n=6) of the vertebral column were treated with surgery (n=4), radiation therapy and chemotherapy (n=6), surgery and chemotherapy (n=2), or surgery, radiation, and chemotherapy (n=8). All dogs died due to their disease; 15 died due to local failure, and five died due to nonvertebral metastasis. Overall median survival time was 135 days, with a range of 15 to 600 days. Of the factors evaluated, only postoperative neurological status had a significant influence on outcome by multivariate analysis. This study supports the overall guarded prognosis for dogs with vertebral neoplasia. Better combinations of surgery, chemotherapy, and radiation therapy remain to be defined for this difficult subset of animal cancer.

Animals↗

PubMedDate not supplied

Surgical treatment of adrenocortical tumors: 21 cases (1990-1996).

Twenty-four adrenocortical tumors were surgically removed from 21 dogs. Histopathological examination confirmed 18 carcinomas and six adenomas. Four dogs died in the perioperative period. Fifteen of the 17 dogs that survived the perioperative period had long-term resolution of their clinical signs. Two dogs with incompletely resected tumors were treated with mitotane to control their clinical signs. Overall median Kaplan-Meier life-table survival for dogs with carcinomas was 778 days (range, one to 1,593 days). Median survival for dogs with adenomas was not reached (range, 11 to 730 days). Histopathological diagnosis, histopathological cellular features, age of the dog, and tumor size were not prognostic of outcome.

Adrenal Cortex Neoplasms↗

PubMedDate not supplied

Idiopathic pneumoperitoneum in a dog.

A 13-year-old, neutered male standard poodle with tachypnea and abdominal distension was diagnosed with pneumoperitoneum. Pneumoperitoneum can be due to a perforated gastrointestinal tract, penetrating abdominal wounds, gas-producing bacterial peritonitis, or it can be iatrogenically introduced during surgery. Idiopathic pneumoperitoneum is a condition diagnosed in humans after exclusion of perforated gastrointestinal tract and other known causes of free intra-abdominal gas. This report suggests that dogs may suffer from a similar syndrome.

Amputation, Surgical↗

PubMedDate not supplied

Adjuvant chemotherapy using cisplatin by subcutaneous administration.

BACKGROUND-MATERIALS: Based on previous polymer release experience, this study was conducted to evaluate the toxicity, efficacy and systemic absorption of cisplatin administered subcutaneously in dogs. METHODS-RESULTS-CONCLUSIONS: Fifty to 70 mg/m2 cisplatin was suspended in saline and injected subcutaneously in 6 dogs as an adjunct to their primary treatment for sarcoma. Gastrointestinal, bone marrow, renal or local tissue toxicity occurred following the first (dogs 1-3,5,6) and second (dogs 1 and 2) treatments. Low, yet measurable levels of platinum were present in serum through day 14 following injection in all dogs. Due to the toxicity seen, all further planned treatments were discontinued and adjuvant regimes were completed with intravenous carboplatin. Although slow systemic absorption of platinum can occur following subcutaneous administration, the degree of toxicity seen following this treatment would indicate that a drug delivery vehicle may be necessary if cisplatin is to be administered for sustained release and adsorption.

Animals↗

PubMedDate not supplied

Intracavitary treatment of soft tissue sarcomas in dogs using cisplatin in a biodegradable polymer.

BACKGROUND: The purpose of this study was to evaluate the toxicity and efficacy against local disease recurrence of soft tissue sarcomas (STS) in dogs using intracavitary cisplatin released from a polymer device (OPLA-Pt). MATERIALS AND METHODS: OPLA-Pt was placed into the wound following marginal (histologically incomplete) resection of STS in 30 dogs (32 tumors) with a median tumor diameter of 3 cm (range = 1-14 cm). Median cisplatin dose was 35.5 mg/m2 (body surface area) with a range of 5.3-133.3 mg/m2. RESULTS: The OPLA-Pt was removed from 9/32 (28%) sites due to local wound complication. Local recurrence occurred in 10/32 (31%) tumors. Higher tumor grade had a significant negative influence on local tumor recurrence (p = 0.031). CONCLUSIONS: The rate of recurrence appeared to be similar using intracavitary cisplatin compared to previous reports of STS treated by marginal surgery followed by radiotherapy. The complication rate indicates the need for further refinement of the polymer/cisplatin system.

Animals↗

PubMedDate not supplied

Status of the p53, Rb and MDM2 genes in canine osteosarcoma.

The key role of p53 and Rb alterations in human osteosarcoma is clear. For example, osteosarcoma is common in individuals inheriting mutant p53 or Rb genes. Osteosarcoma in dogs is similar to humans by histology, site, gender ratio and several other biological parameters. To study whether this similarity extends to the molecular level, 21 canine osteosarcomas were analyzed for alterations of p53, Rb and MDM2. MDM2 is a normal cell protein which antagonizes p53, amplification is seen in some human sarcomas. The gross structure of the p53, Rb and MDM2 genes was examined by Southern blotting. No deletions or rearrangements of the p53 or Rb genes were detected. The absence of gross gene alterations affecting these tumor suppressor genes is a significant difference between the disease in dogs and humans, since rearrangements or deletions of the p53 or Rb genes occur in 20-30 per cent of human osteosarcomas. The MDM2 gene appeared to be duplicated in one canine tumor but no cases of significant amplification were detected. Expression of normal Rb was detected in all cases. Mutations of the p53 gene were found in 38 percent of canine osteosarcomas. Analysis of mutations revealed a predominance of spontaneous mutation. These finding emphasize the key role that alterations of p53 have in the development of osteosarcoma in dogs and humans.

Animals↗