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Successful treatment of an equine preputial fibrosarcoma using 5-fluorouracil/evaluation of the treatment using quantitative PCNA and Ki67 (MIB 1) immunostaining. (case report).

An 18-month-old cross-bred Fjord pony colt presenting a fibrosarcoma of the prepuce with severe infiltrative growth, was treated by topical application of 5-fluorouracil. Biopsies were taken before and after a treatment period of 2 months. As a control, preputial tissue from a healthy horse was biopsied. Tissue sections were stained immunohistochemically for Proliferating Cell Nuclear Antigen (PCNA) and Proliferation related factor--Ki67 (MIB1). Using computerized quantitative image analysis of these sections, Mitotic index (PCNA), Growth Fraction (Ki67) and total nuclear area percentage of the dermis were calculated. The Mitotic index, growth fraction and total nuclear area percentage were significantly (P < 0.001) reduced at the end of the treatment period compared to the initial biopsy tissue, but they still were significantly higher than the control values, due to a remnant inflammatory reaction to the cytostatic drug. After treatment of the lesion, the pony fully recovered with no visible residual lesions on the prepuce. On follow-up 6 months after treatment, the horse showed no signs of recurrence. The success of the present treatment should encourage further clinical trials in cases of malignant fibrous tumours of skin in horses. The quantitative analysis of cell proliferation in biopsies can be used to evaluate treatment follow-up.

Animals↗

Primary fibrosarcoma of the heart.

A case of primary fibrosarcoma of the heart, which was diagnosed in a 17 year old man, is presented. Extensive tumour resection and postoperative radiation therapy was carried out. The patient is alive after 18 months after the operation. Although these tumours are associated with very poor survival, early diagnosis and combined therapy may prolong life expectancy.

Adolescent↗

Primary ovarian fibrosarcoma with long-term survival: a report of two cases.

We report on two cases of primary ovarian fibrosarcoma detected in two women aged 44 and 34 years old. In the first case, an 18 x 17 x 10 cm multilobular tumor was detected in the left ovary. In the second case, a 13 x 9 x 3 cm and a 7 x 6 x 2 cm tumor were found in the left and right ovaries, respectively. In addition, a large quantity of ascitic fluid was detected. In both cases, a total hysterectomy with bilateral adnexectomy and an omentectomy were performed. No evidence of lymph-node enlargement was detected in either case. Microscopic findings demonstrated densely, cellular spindle-shaped tumor cells with increased mitotic activity (17 and 8/10 high-power fields, respectively). Immunohistochemical analyses showed that tumor cells were positive for vimentin and negative for smooth muscle actin, S-100, and estrogen receptor. Progesterone receptor was positive only in the second case. After surgery, both patients received several courses of combination chemotherapy. Neither patient demonstrated any evidence of disease recurrence during follow-up for 10 years and 5 years, respectively.

Adult↗

Surgical excision of soft tissue fibrosarcomas in cats.

OBJECTIVE: The purpose of this study was to determine the tumor-free interval and survival times of cats who had one (group 1) or more (group 2) surgeries, or surgery and radiation therapy (RTH) (group 3) for treatment of soft tissue fibrosarcomas (FSA). STUDY DESIGN: Retrospective study. ANIMALS OR SAMPLE POPULATION: 45 client-owned cats. METHODS: Medical records of cats with soft tissue FSA were examined. Vaccination and feline leukemia virus (FeLV) status, age, sex, breed, tumor location, number of surgeries, completeness of excision, and histopathological grade were evaluated to correlate with tumor-free interval and survival periods. RESULTS: Overall median tumor-free interval and survival times were 10 and 11.5 (range, 1 to 40) months. Median tumor-free interval and survival times were more than 16 months each in group 1, more than 5 and 13 months in group 2, and 4.5 and 9 months in group 3. Age, sex, breed, vaccination or FeLV status, tumor location, or histopathological grade did not affect median tumor-free interval or survival times (P > .05). Cats with complete excisions had significantly longer median tumor-free interval (> 16 versus 4 months) and survival time (> 16 versus 9 months) than those with incomplete excisions (P = .008). Radiation therapy did not seem to extend tumor-free interval and survival times (P = .013). However, most group 3 cats had incomplete surgical excisions, resulting in recurrent or progressive disease. CONCLUSIONS: Complete surgical excision of FSA in cats is possible and can be curative. CLINICAL RELEVANCE: Aggressive surgical excision with wide margins appears to contribute to extended tumor-free interval and survival times in cats with soft tissue FSA. Controlled prospective studies are needed to determine the efficacy of RTH in treatment.

Animals↗

Vertebrectomy, bone allograft fusion, and antitumor vaccination for the treatment of vertebral fibrosarcoma in a dog.

OBJECTIVE: To describe the surgical technique of vertebrectomy with bone allograft fusion and the use of antitumor vaccine for the treatment of a primary vertebral neoplasm in a dog. STUDY DESIGN: Case Report. ANIMALS OR SAMPLE POPULATION: A 3 year old 32 kg female spayed mixed breed dog with progressive paraplegia. METHODS: Myelography was performed to identify an L5 lytic lesion with spinal cord compression. A dorsal laminectomy was performed to decompress the spinal cord and obtain biopsies. Pathologic fracture of the vertebral body two days later was treated with L5 vertebrectomy, cortical allograft implantation, and bilateral plating from L4 to L6. Tumor samples were used to create an autologous cytokine-gene-engineered tumor cell vaccine. Recheck radiographs and neurologic examinations were obtained 1, 2, 7, and 13 months after surgery. RESULTS: The histopathologic diagnosis was fibrosarcoma. Although slight osteopenia of the allograft was noted thirteen months after surgery, the allograft and plate fixation remained stable. The patient tolerated the antitumor vaccination protocol well. Two years after the procedures the dog was able to ambulate normally but remained urinary and fecal incontinent. CONCLUSIONS AND CLINICAL RELEVANCE: Vertebrectomy and cortical allograft implantation with plating permitted this patient to return to a functional lifestyle with its owners.

Animals↗

Expression of the 72-kD heat shock protein is induced by ultraviolet A radiation in a human fibrosarcoma cell line.

The 72-kD heat shock protein (hsp72) belongs to a family of stress inducible proteins (heat shock proteins, hsp) and its expression is associated with increased survival of cells in culture following exposure to ultraviolet radiation (UV). Hsp72 can be induced by a number of stresses, including heat, cold, and toxic chemicals. The purpose of this study was to evaluate whether UV is able to activate transcription of hsp72. The human fibrosarcoma cell line HT1080 was used for these experiments because hsp72 is not detectable in these cells under normal culture conditions. Cells were exposed to UVA and UVB using a solar simulating source and hsp72 was determined in whole cell extracts by immunoblotting. For inhibition of mRNA and protein synthesis cordycepin (20 microg/ml) and cycloheximide (10 microg/ml) were added to the cultures, respectively. UVA-induced lipid peroxidation was inhibited by alpha-tocopherol and butylated hydroxytoluene (BHT). UVA but not UVB induced hsp72 with maximal expression at 40 J/cm2, 8-12 h after exposure. Induction was blocked by cordycepin as well as by cycloheximide indicating that both, mRNA and protein synthesis, are required for UVA-induction of hsp72. Inhibition of cell lipid peroxidation with alpha-tocopherol and BHT had no effect on hsp72 expression. These results suggest that induction of hsp72 is part of an adaptive response mechanism in human cells to UV-related stress.

Antineoplastic Agents↗

Infantile fibrosarcoma in the mandible: case report.

A case of an infantile fibrosarcoma in the mandible is described. The primary tumor was seen in a 2.5 yr-old boy. In spite of repeated surgical interventions the tumor recurred five times during a 15-yr period, but no metastases have been observed. The difficulty in arriving at a correct histopathologic diagnosis on an unusual tumor in the oral region is demonstrated by the fact that 16 consulted pathologists suggested a long list of different tumors. The treatment of choice seems to be radical surgery. The patient has remained well and without recurrence for the last 7 yr.

Adolescent↗

Lingual fibrosarcoma induced by 7, 12-dimethylbenzanthracene in the rat.

A single injection of 5 mg of 7, 12-dimethylbenzanthracene (DMBA) resulted in a high incidence of lingual fibrosarcoma in 67 Wistar rats. No metastases were found. We studied the influence of age and sex on the incidence, latency of tumors, loss of weight and the spontaneous survival of animals. The method described offers an experimental model for the study of cachexia resulting from upper digestive and respiratory tract cancer.

9,10-Dimethyl-1,2-benzanthracene↗

Growth patterns of pulmonary metastases and primary tumours from five murine fibrosarcoma cell clones.

The growth patterns, including the size, shape and regional preferences, of lung metastases from five murine fibrosarcoma cell clones were studied. Spontaneous metastases developed from tumours formed by subcutaneous inoculation of the cell clones. Lung colonies (experimental metastases) were established by i.v. injection of cells. The numbers of both spontaneously and experimentally formed subpleural lung metastases were counted through a stereomicroscope. The fraction of colonies that was located subpleurally was determined in histological sections of lungs. The growth kinetics of clonally derived primary tumours, and the number of spontaneous and experimental lung metastases, differed greatly between certain cell clones. The number of spontaneous lung metastases was correlated with the maximum size of primary tumours. No close correlation was observed between the size of the primary tumours and the size of experimental metastases. There were differences between the cell clones in the shape and regional preferences of their lung deposits. The subpleural colonies were generally larger than the intrapulmonary ones. Thus, both the regional distribution and the growth pattern of lung deposits differed between the clones.

Animals↗

Radiation therapy and surgery for fibrosarcoma in 33 cats.

Thirty-three cats with histologically confirmed fibrosarcomas were treated with radiation therapy followed by surgery. The median (95% confidence interval) disease free interval and overall survival were 398 (261,924) and 600 (lower limit 515) days, respectively. There were 19 treatment failures; 11 cats had only local recurrence, 4 cats developed metastatic disease, 3 cats had local recurrence followed by metastasis, and 1 cat developed simultaneous local and distant disease. Twelve cats are alive and disease free. Two cats died without evidence of treatment failure. The presence of tumor cells at the margin of resected tissue after radiation was the only variable which influenced treatment success. The median (95% confidence interval) disease free interval in 5 cats with tumor cells at the margin of the resected specimen was 112 (94,150) days versus 700 (lower limit 328) days for 26 cats with negative tumor margins, p < 0.0001. We did not identify a relationship between tumor volume, number of prior tumor excisions, concomitant use of chemotherapy or various descriptors of the radiation therapy technique and disease free interval.

Animals↗

A urinary bladder fibrosarcoma in a young dog.

A 14-month-old female dog, Gos d'Atura Catala was presented for a 7-month-history of reoccurring urinary tract infection. Using sonography, a focal multilobulated thickening of the urinary bladder wall was discovered. The solid mass was arising from the area of the ureteral papllDae and bulging into the lumen of the bladder neck. The wall of the urethra was uniformly thickened. These findings were not considered typical for a generalized urinary tract infection but more indicative of local severe inflammation, neoplasia or hyperplasia in the area of the ureteral openings. The thickening of the urethra was suggestive of urethritis or neoplastic infiltration. Signs of metastasis were not detected on the thoracic radiographs or in the remainder of the abdominal ultrasound examination. A surgical excision of the multilobulated mass was performed and histologic examination was conducted. A fibrosarcoma in the lamina propria of the urinary bladder wall was diagnosed. Because of reoccurence of hematuria and unresponsiveness to therapy the dog was euthanized. Postmortem examination confirmed the diagnosis of fiborsarcoma in the urinary bladder. Additionally, neoplastic infiltration of the urethral wall and metastasis in the lungs and liver were detected histopathologically.

Animals↗

Ginsenoside 20(S)-protopanaxadiol inhibits the proliferation and invasion of human fibrosarcoma HT1080 cells.

Ginsenoside 20(S)-protopanaxadiol, one of metabolites of ginseng saponins, has been well characterized to possess the pleiotropic anticancer capabilities in several cancer cell lines. The object of this study was to investigate the effects of ginsenoside 20(S)-protopanaxadiol on the invasion in vitro and the expression of matrix metalloproteinase-2 in human fibrosarcoma HT1080 cells in absence of cytotoxicity. Our results showed that ginsenoside 20(S)-protopanaxadiol exerted a concentration-dependent inhibitory effect on the proliferation of HT1080 cells (IC50 was 76.78+/-2.24 microM, 48 hr). Treatment with 20(S)-protopanaxadiol significantly declined the invasive capacity of HT1080 cells compared to the control cells (P<0.01) in the in vitro invasion assay. Further analysis with gelatin zymography and western blotting revealed that both the activity and the expression of matrix metalloproteinase-2 decreased dramatically in a concentration-dependent manner (P<0.01). Taken together, these results indicated that ginsenoside 20(S)-protopanaxadiol is able to inhibit the invasiveness of HT1080 cells significantly in vitro and this action may be primarily due to down-regulating the expression of matrix metalloproteinase-2. Ginsenoside 20(S)-protopanaxadiol, a metabolite of ginseng, may be applied as a potential therapeutic agent in the prevention and treatment of cancer.

Antineoplastic Agents, Phytogenic↗

Non-H-2-linked genetic control of resistance to BALB/c fibrosarcoma Meth-A.

The genetic control of hybrid resistance to BALB/c fibrosarcoma Meth-A was investigated. A Meth-A tumour grew slower in (BALB/c x C57BL/6)F1 and reciprocal hybrid mice than in syngeneic BALB/c mice and was also found to grow slower in females than in males. Significant F1 resistance was demonstrated after both subcutaneous and intraperitoneal injection of tumour cells. However, (BALB/c x DBA/2)F1 mice did not show any significant resistance to Meth-A. In H-2 linkage studies of [BALB/c x (BALB/c x C57BL/6)] backcross mice, no statistically significant differences in the resistance of H-2 heterozygotes and homozygotes to Meth-A were observed. These results indicated that F1 hybrid resistance to Meth-A was controlled by non-H-2-linked resistance factor(s). No linkage was observed between resistance to Meth-A and coat colour c- and b-loci.

Animals↗

Biochemical analysis of a public H-2 specificity revealed by an anomalous reaction of an alloantiserum with a chemically induced C57BL/10 fibrosarcoma.

D-25 is a H-2 alloantiserum produced in (B10.D2 X C3H.NB) (H-2d X H-2p)F1 mice after immunization with B10.RIII(H-2r) cells, and which is known to recognize the H-2.25 public antigen on H-2k haplotypes. The "anomalous" reaction of D-25 with a partially purified deoxycholate-solubilized glycoprotein of B10-1 (H-2b) fibrosarcoma was studied with various biochemical techniques. The 125I-labelled precipitates were analysed both in one- and two-dimensional SDS-PAGE and by a partial proteolysis peptide mapping (Cleveland's mapping). The results indicate first that the D-25-related antigen was a genuine H-2 antigen normally associated with the B2-microglobulin, second that this antigen was borne by the Kb but not Db gene products, and finally that D-25 was able to precipitate the same antigen on normal H-2b spleen cells. We conclude that this serum recognized a normal H-2 specificity shared by H-2b and H-2r haplotypes and tentatively identified as the public antigen H-2.54 which for the first time could be assigned to the K but not to the D region of the H-2b haplotype.

Animals↗

Isolation of the MHC genes encoding the tumour-specific class I antigens expressed on a murine fibrosarcoma.

The C3H UV-induced fibrosarcoma, 1591, is highly immunogenic and, therefore, is readily rejected when transplanted into immunocompetent syngeneic recipients. Previous analysis of 1591 with tumour-specific or H-2-reactive monoclonal antibodies revealed that this antigenicity might be due to the expression of two novel class I major histocompatibility complex (MHC) antigens. In this report we describe the molecular cloning and initial characterization of three genes which account for all of the unique serological class I reactivities observed on this tumour. These include two distinct, but highly conserved, H-2L-like genes, and a third gene the product of which bears determinants which are characteristic of both the tumour and of class I products of the H-2k haplotype. Moreover, each of these genes contains a polymorphic restriction enzyme fragment which is detected in the class I sequences of 1591 relative to normal C3H tissue. Since the expression of these polymorphic class I sequences is relevant to the immunogenicity of 1591, the mutational events by which these genes were generated may be significant to the immunobiology of this tumour.

Animals↗

NK sensitivity, H-2 expression and metastatic potential: analysis of H-2Dk gene transfected fibrosarcoma cells.

We have used the 3-Methylcholanthrene induced T-10 fibrosarcoma tumour cell system (H-2b xH-2k)F1 to elucidate the possible correlation between metastatic potential, expression of individual H-2 antigens and susceptibility to NK cells. Transfection of the non-metastatic and NK sensitive IC9 cells (Db+, Dk-, Kb-, Kk-) with the H-2Dk gene, altered the metastatic phenotype of the parental cells, yet had no effect on the susceptibility of these tumour cells to lysis by NK and did not elicit a specific CTL response in syngeneic hosts. Variants of the metastatic and NK resistant IE7 clone (Db+, Dk+, Kb-, Kk-), lacking H-2Dk, were selected by treatment with monoclonal anti H-2Dk antibodies and complement. These variants were sensitive to NK and poorly or non metastatic. Retransfection of 'Dk' 'loss' variants with the H-2Dk gene, resulted in the isolation of several clones expressing a wide range of metastatic phenotypes but maintained sensitivity to NK. These results indicate that the H-2D region of the MHC and or closely linked genes may be involved in the complex interrelationship between target susceptibility to NK and metastasis.

Animals↗

Resistance to photodynamic therapy in radiation induced fibrosarcoma-1 and Chinese hamster ovary-multi-drug resistant. Cells in vitro.

A degree of resistance to photodynamic therapy (PDT) has been induced in radiation-induced fibrosarcoma-1 (RIF-1) tumor cells by repeated photodynamic treatment with Photofrin (4 or 18 h incubation) in vitro to the 0.1-1% survival level, followed by regrowth from single surviving colonies. The resistance is shown as increased cell survival in the strain designated RIF-8A, compared to the wild-type RIF-1 cells, when exposed to increasing Photofrin concentration for 18 h incubation and fixed light exposure. No difference was found between RIF-1 and RIF-8A in the uptake of Photofrin per unit cell volume at 18 h incubation. Resistance to PDT was also observed in Chinese hamster ovary-multi-drug resistant (CHO-MDR) cells compared to the wild-type CHO cells, possibly associated with decreased cellular concentration of Photofrin in the former. By contrast, the PDT-resistant RIF-8A cells did not show any cross-resistance to Adriamycin, nor was there any significant drug concentration difference between RIF-1 and RIF-8A. These findings suggest that different mechanisms are responsible for PDT-induced resistance and multi-drug resistance.

Animals↗

Photofrin accumulation in malignant and host cell populations of a murine fibrosarcoma.

Photofrin (25 mg/kg) was administered to the FsaR fibrosarcoma-bearing mice (either syngeneic or severe combined immunodeficient [SCID]) and the tumors were excised 24 h later. The photosensitizer content in the cells dissociated from tumor tissue was analyzed using flow cytometry. Staining the cell suspensions with the monoclonal antibodies against specific membrane markers served to identify the malignant cells and various types of host immune cells infiltrating the tumor. Photofrin content was also examined in the cells from normal tissues of the tumor-bearing mice (spleen, heart muscle, peritoneal macrophages). The results show a marked heterogeneity in the Photofrin cellular content of FsaR tumor, particularly within the population of tumor-associated macrophages (TAM). The Photofrin levels in some TAM were lower or similar to those in the malignant cells. In contrast, a subpopulation of TAM accumulated very high levels of the photosensitizer, which exceeded by far the levels found in the other tumor cell populations. This TAM fraction was characterized by particularly high expression of interleukin-2 receptors and increased cell size and granularity when compared to the other TAM, which suggests that these macrophages are in the activated state. Their average Photofrin content was almost 13 times higher than in the malignant cells. The lowest photosensitizer levels in the tumor were found in tumor-infiltrating leukocytes other than TAM. In FsaR tumors growing in SCID mice, the pattern of Photofrin distribution in TAM and other cellular populations was similar to that found in tumors growing in syngeneic mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗