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PubMed2005

Efficacy of Wnt-1 monoclonal antibody in sarcoma cells.

BACKGROUND: Sarcomas are one of the most refractory diseases among malignant tumors. More effective therapies based on an increased understanding of the molecular biology of sarcomas are needed as current forms of therapy remain inadequate. Recently, it has been reported that Wnt-1/beta-catenin signaling inhibits apoptosis in several cancers. In this study, we investigated the efficacy of a monoclonal anti-Wnt-1 antibody in sarcoma cells. METHODS: We treated cell lines A-204, SJSA-1, and fresh primary cultures of lung metastasis of sarcoma with a monoclonal anti-Wnt-1 antibody. Wnt-1 siRNA treatment was carried out in A-204. We assessed cell death using Crystal Violet staining. Apoptosis induction was estimated by flow cytometry analysis (Annexin V and PI staining). Cell signaling changes were determined by western blotting analysis. RESULTS: We detected Wnt-1 expression in all tissue samples and cell lines. Significant apoptosis induction was found in monoclonal anti-Wnt-1 antibody treated cells compared to control monoclonal antibody treated cells (p < 0.02). Similarly, we observed increased apoptosis in Wnt-1 siRNA treated cells. Blockade of Wnt-1 signaling in both experiments was confirmed by analyzing intracellular levels of Dishevelled-3 and of cytosolic beta-catenin. Furthermore, the monoclonal anti-Wnt-1 antibody also induced cell death in fresh primary cultures of metastatic sarcoma in which Wnt-1 signaling was active. CONCLUSION: Our results indicate that Wnt-1 blockade by either monoclonal antibody or siRNA induces cell death in sarcoma cells. These data suggest that Wnt-1 may be a novel therapeutic target for the treatment of a subset of sarcoma cells in which Wnt-1/beta-catenin signaling is active.

Adaptor Proteins, Signal Transducing↗
PubMed1986

Soft-tissue and bone sarcoma histopathology peer review: the frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience.

Histopathologic peer review of specimens from 216 consecutive patients with soft-tissue or bone sarcomas on Southeastern Cancer Study Group protocols was performed by a panel of three pathologists. Subtype of sarcoma, degree of confidence in diagnosis, and grade were compared with agreement or disagreement in pathologic opinion from the primary member institution v the pathology review panel. The most common soft-tissue sarcoma was leiomyosarcoma, followed by malignant fibrous histiocytoma, fibrosarcoma, liposarcoma, malignant schwannoma, and rhabdomyosarcoma. There was total agreement between the primary pathologist and reviewer in 66% of cases. However, 12 cases (6%) were considered on review to not be sarcomas. In 27% of cases the subtype of sarcoma was felt to be incorrect by reviewers. Discordant diagnoses were more common when the confidence of the pathologist was less and when the tumor was of higher grade. There was no improvement in frequency of agreement in the second half of the study, despite educational workshops. We conclude that histologic peer review is important in sarcoma studies and is essential in many patients with presumed sarcomas.

Bone Neoplasms↗
PubMed1993

An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas.

PURPOSE AND METHODS: Doxorubicin alone or with dacarbazine (DTIC; AD) is considered the best available therapy for metastatic adult sarcomas. Ifosfamide is active in sarcomas that have failed to respond to a doxorubicin-based regimen. This study was designed to determine if ifosfamide added to doxorubicin and DTIC (ADI) significantly effects toxicity, response rate, and survival. Patients with measurable metastatic or unresectable sarcoma were randomized to receive AD or ADI. Patients with chondrosarcomas, fibrosarcomas, and other sarcomas of bone were eligible, although those with osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi's sarcoma, and mesothelioma were excluded, as were patients with prior chemotherapy for sarcoma or prior doxorubicin. RESULTS: Between 1987 and 1989, 340 eligible patients were randomized. Significantly more myelosuppression, a higher response rate (17% v 32%; P < .002) and longer time to progression (4 v 6 months; P < .02) were observed for patients who received ifosfamide. An overall survival advantage for the two-drug regimen (12 v 13 months; P = .04) was not significant by multivariate analysis. CONCLUSION: In all three randomized trials of doxorubicin with and without ifosfamide (Eastern Cooperative Oncology Group [ECOG], European Organization for Research and Treatment of Cancer [EORTC], and this study), the response rate was higher for the ifosfamide-containing arm, significantly so in this and the ECOG studies. An improved response rate may be particularly important for the preoperative management of high-grade, borderline resectable lesions or pulmonary metastases, particularly in younger patients. In older patients, or for low-to intermediate-grade lesions, doxorubicin and DTIC followed by ifosfamide on progression is preferred.

Adolescent↗
PubMed1997

High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence.

PURPOSE: To evaluate the efficacy and feasibility of high-dose ifosfamide (HDI) at a total dose of 14 g/m2 per cycle with mesna in combination with granulocyte colony-stimulating factor (G-CSF) in adult patients with sarcomas. PATIENTS AND METHODS: Between July 1991 and February 1994, 74 patients with sarcomas (37 bone and 37 soft tissue) were treated on two simultaneous phase II studies that evaluated HDI given as a continuous infusion over 74 hours. G-CSF was started on day 5 at 5 microg/kg/d until recovery of granulocyte count. Additionally, between March 1993 and March 1994, 15 similar patients with previously treated bone or soft tissue sarcomas were treated on a pilot study in which the same total dose of ifosfamide was administered by a bolus schedule, along with mesna and G-CSF. Patients were treated until maximal response, and where possible, surgical resection of gross disease was performed. RESULTS: Seventy-two patients from the phase II study using continuous infusion are assessable for response. Four complete responses (CRs) and 17 partial responses (PRs) were noted, for an overall response rate of 29% (95% confidence interval [CI], 19% to 39%). The response rate was 40% (95% CI, 24% to 56%) for bone sarcomas and 19% (95% CI, 6% to 32%) for soft tissue sarcomas. Fourteen patients from the pilot study that used a bolus schedule are assessable for response. One CR and seven PRs were noted, for an overall response rate of 57% (95% CI, 31% to 83%) and a response rate of 45% for soft tissue sarcomas. Two patients developed grade 3 to 4 renal toxicity, three developed grade 3 CNS toxicity, one had possible grade 3 cardiac toxicity, and two developed severe painful peripheral neuropathy. There were no treatment-related deaths. CONCLUSION: HDI at 14 g/m2 with mesna and G-CSF is an active salvage regimen for patients with bone and soft tissue sarcomas. There is a definite positive dose-response curve, and bolus administration appears to be more active than continuous infusion.

Adolescent↗
PubMed2000

Impact of neoadjuvant chemotherapy on postoperative morbidity in soft tissue sarcomas.

PURPOSE: The purpose of this study was to test the hypothesis that neoadjuvant chemotherapy (NeoCT) does not increase morbidity in patients undergoing radical surgery for soft tissue sarcomas. PATIENTS AND METHODS: The records of 309 patients who presented to The University of Texas M.D. Anderson Cancer Center for definitive surgical management of primary soft tissue sarcomas were retrospectively reviewed. One hundred five patients who received NeoCT were compared with 204 patients who had surgery first (Surg). Patients had extremity sarcomas (71 NeoCT patients and 130 Surg patients) or retroperitoneal/visceral sarcomas (34 NeoCT and 74 Surg). RESULTS: NeoCT patients had larger tumors (median, 12 v 8 cm), more frequently had high-grade tumors (90% v 64%), and were younger (median age 47 v 55 years). The incidence of surgical complications was not different for NeoCT patients than for Surg patients, both in those with extremity sarcomas (34% v 41%) and in those with retroperitoneal/visceral sarcomas (29% v 34%). The most common complications were wound infections and other wound complications. Preoperative radiation therapy, autologous flap coverage, and extremity tumors were associated with increased wound complications. No significant differences in length of hospital stay, rate of readmission, or rate of reoperation for complications were found between the NeoCT and Surg groups. One of the three postoperative deaths in our series occurred in the NeoCT group. CONCLUSION: In this retrospective review, there was no evidence that NeoCT increased postoperative morbidity in patients with soft tissue sarcomas. Prospective, randomized studies are needed to confirm these results.

Antibiotics, Antineoplastic↗
PubMed2003

Immunohistochemical expression of p53, fibroblast growth factor-b, and transforming growth factor-alpha in feline vaccine-associated sarcomas.

Fifty feline sarcomas associated with vaccine-site injection were evaluated to determine the immunohistochemical expression of p53 protein, basic fibroblast growth factor (FGF-b), and transforming growth factor-alpha (TGF-alpha). Forty-one tumors (82%) were fibrosarcomas (FS), eight (16%) were malignant fibrous histiocytomas (MFH), and one (2%) was a chondrosarcoma (CS). Overexpression of p53 protein was observed in the nuclei of tumor cells in 28 (56%) sarcomas; FGF-b expression was found in the cytoplasm of tumor cells in 40 (80%) feline sarcomas, but the staining was more intense in the spindle-shaped cells of FS than in polygonal or round cells of MFH. The single CS faintly expressed FGF-b. The majority of feline vaccine-associated sarcomas (43 of 50, 86%) expressed moderate or intense staining for TGF-alpha in the cytoplasm of tumor cells. Heterogeneous immunolabeling for p53, FGF-b, and TGF-alpha was present in neoplastic, multinucleated giant cells. Intense expression of FGF-b was statistically associated with younger cats (P < 0.01) and with tumors with nodular growth patterns (P = 0.02). In addition, sarcomas negative for p53 protein expressed FGF-b more frequently than did p53-positive tumors (P = 0.04). The frequency of FGF-b immunostaining was significantly higher in sarcomas with intense expression of TGF-alpha (P = 0.05). Immunohistochemical detection of p53 protein, FGF-b, and TGF-alpha suggests that these growth-regulating proteins may play different roles in the development of sarcomas associated with vaccine sites.

Animals↗
PubMed2005

Prognostic significance of augmented metallothionein (MT) expression correlated with Ki-67 antigen expression in selected soft tissue sarcomas.

In soft tissue sarcomas, the most important prognostic criteria include extent of malignancy (G), size of the tumour and intensity of Ki-67 antigen expression. In recent times expression of metallothionein (MT) in cells of some malignant processes of epithelial origin was found to correlate with intensity of Ki-67 antigen expression and to carry a possible prognostic significance. The present study aimed at a demonstration of prognostic value of MT expression and at comparing it with Ki-67 antigen expression and G grade in selected soft tissue sarcomas. Immunohistochemical studies were performed on paraffin sections in 54 cases of malignant fibrous histiocytoma (MFH), 18 cases of liposarcoma and 20 cases of synovial sarcoma. The extent of MT and Ki-67 antigen expression was evaluated and an attempt was made to correlate the results with each other and with grade of the tumour. Expression of MT was evident both in the cytoplasm and in cell nuclei of all studied sarcomas. The most pronounced MT expression was noted in MFH-type tumours. The extent of Ki-67 antigen expression was similar in MFH and liposarcoma and was the lowest in synovial sarcoma. In MFH, liposarcoma and synovial sarcoma a pronounced positive correlation was documented between expression of MT and Ki-67 antigen (r=0.85; p<0.001; r=0.93, p<0.0001; r=0.79, p<0.0001). In all types of the tumours a positive relation was detected between MT expression, expression of Ki-67 and G grade of malignancy in the tumour. Moreover, patients with higher MT expression in the studied tumours demonstrated a shorter survival. MT expression in soft tissue tumours of MFH, liposarcoma and synovial sarcoma type strongly correlated with intensity of proliferation (Ki-67) and G grade and could be useful in defining the extent of malignancy and in prognostic appraisal in the tumours.

Humans↗
PubMed2002

Management of AIDS-related Kaposi's sarcoma: advances in target discovery and treatment.

Kaposi's sarcoma is the most common tumor arising in HIV-infected patients and is an AIDS-defining illness by the Centers for Disease Control guidelines. Recent advances in the elucidation of the pathogenesis of KS are uncovering potential targets for KS therapies. Such targets include the processes of angiogenesis and cellular differentiation and the Kaposi's sarcoma herpesvirus/human herpesvirus-8. With the increasing recognition that effective antiretroviral regimens are associated with both a decreased proportion of new AIDS-defining Kaposi's sarcoma cases and a regression in the size of existing Kaposi's sarcoma lesions, most, if not all, Kaposi's sarcoma patients should be advised to take antiretroviral drugs that will maximally decrease HIV-1 viral load. Five agents are currently approved by the US FDA for the treatment of Kaposi's sarcoma; alitretinoin gel for topical administration; and liposomal daunorubicin, liposomal doxorubicin, paclitaxel and interferon-alpha for systemic administration. Many more agents, particularly angiogenesis inhibitors and other pathogenesis-targeted therapies are in early clinical development. Over the next 5 years, we may see even more of these pathogenesis-targeted therapies in trials and just as important we may identify, develop and validate clinically practical tools for assessing the biological effects of these therapies. The next 5 years may also bring a better understanding of the pharmacokinetic interactions among the many agents in the Kaposi's sarcoma and AIDS armamentariums.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Human herpesvirus 8 (HHV-8) and the etiopathogenesis of Kaposi's sarcoma.

OBJECTIVE: To review the current literature on human herpesvirus 8 with particular attention to the aspects related to the etiopathogenesis of Kaposi's sarcoma. MATERIALS AND METHODS: The authors searched original research and review articles on specific aspects of human herpesvirus 8 infection, including virology, epidemiology, transmission, diagnosis, natural history, therapy, and Kaposi's sarcoma etiopathogenesis. The relevant material was evaluated and reviewed. RESULTS: Human herpesvirus 8 is a recently discovered DNA virus that is present throughout the world but with major geographic variation. In the Western world, the virus, transmitted mainly by means of sexual contact, is strongly associated with Kaposi's sarcoma and body cavity-based lymphoma and more controversially with multiple myeloma and other non-proliferative disorders. There is no specific effective treatment, but HIV protease inhibitors may play an indirect role in the clearance of human herpesvirus 8 DNA from peripheral blood mononuclear cells of HIV-infected patients. Human herpesvirus 8 DNA is present in saliva, but there are as yet no documented cases of nosocomial transmission to health care workers. The prevalence of human herpesvirus 8 among health care workers is probably similar to that in the general population. CONCLUSION: Human herpesvirus 8 appears to be, at least in Western Europe and United States, restricted to a population at risk of developing Kaposi's sarcoma. Human herpesvirus 8 certainly has the means to overcome cellular control and immune responses and thus predispose carriers to malignancy, particularly Kaposi's sarcoma. The wide diffusion of Human herpesvirus 8 in classic Kaposi's sarcoma areas appears to represent an important factor in the high incidence of the disease. However, additional co-factors are likely to play a role in the development of Kaposi's sarcoma.

HIV Infections↗
PubMed1979

Immunotherapeutic effect of allogeneic tumor cells on the growth of autochthonous 3-methylcholanthrene-induced sarcomas in rats.

The tumor-inhibitory effect of injections of allogeneic tumor cells was observed. Established autochthonous sarcomas induced in the subcutaneous tissue of rats by 3-methylcholanthrene (MCA) were treated with immunization by using allogeneic Hirosaki sarcoma cells. When MCA-induced sarcomas grew to approximately 1 cm in mean diameter, Hirosaki sarcoma cells were inoculated into various tissues of primary tumor-bearing rats. Immunizing procedures consisted of intraperitoneal and subcutaneous injections in one experimental group, and of intradermal and intraperitoneal injections in another. Significantly inhibitory effect on the growth of autochthonous sarcomas was observed in the initial stage up to 2 cm in diameter as compared with that of control sarcomas. No significant inhibition was seen in the course of the growth of sarcomas larger than 2 cm in diameter. This results may indicate that immunotherapy by using allogeneic tumor cells should be considered to be valuable for the treatment of human cancer.

Animals↗
PubMed2003

Oral Kaposi sarcoma associated with severe alveolar bone loss: case report and review of the literature.

BACKGROUND: In AIDS patients who present with an oral neoplasm, Kaposi sarcoma is the tumor most frequently encountered, comprising 50% to 80% of all tumor occurrences. However, oral Kaposi sarcoma associated with erosion of underlying bone is a relatively rare finding. This report and review of the literature documents a case of AIDS-related oral Kaposi sarcoma exhibiting severe bilateral erosion of the maxillary alveolar ridges. METHODS: An HIV-seropositive male with extensive maxillary Kaposi sarcoma and associated bilateral alveolar bone erosion presented for dental evaluation subsequent to radiation therapy. Clinical and radiographic examinations were performed. Medical and dental histories were procured and supplemented with consultations from the patient's primary physician and radiation oncologist. Maxillary edentulation with surgical revision for primary closure was the treatment of choice for management of the dentoalveolar pathology. A maxillary immediate treatment denture was designed to obturate anticipated antral communications with the maxillary sinus. RESULTS: Surgical and prosthetic treatments were completed, but complicated by an oral-antral perforation that subsequently healed without complication. Soft tissue biopsies obtained during surgery revealed no evidence of residual Kaposi sarcoma. CONCLUSIONS: Although AIDS-related oral Kaposi sarcoma is a relatively common finding, erosion of subjacent alveolar bone is uncommon. Treatment of the tumor with subsequent dental reconstruction can be complicated by the severe lack of bone, surgical perforation of the maxillary sinus, and lack of stable teeth to serve as abutments. Significant advances in understanding the pathogenesis of AIDS-related Kaposi sarcoma have occurred in the last decade. HHV-8 and various inflammatory cytokines have been implicated in the pathogenesis and are likely to become the primary targets for therapeutic intervention.

AIDS-Related Opportunistic Infections↗
PubMed1999

A risk and benefit assessment of treatment for AIDS-related Kaposi's sarcoma.

Kaposi's sarcoma is the most common malignancy observed in patients with HIV-1 infection, and causes considerable morbidity and, when the lungs are involved, mortality. Therapy should be based on an evaluation of prognostic factors, in particular the extent and rate of tumour growth, patient symptoms, immune system condition and concurrent complications of AIDS. Nevertheless, considering the palliative role of Kaposi's sarcoma therapy, the potential benefits of therapy must be weighed against the high risk of adverse effects. Therefore, quality of life assessment is an integral component of therapeutic decisions. Localised Kaposi's sarcoma cutaneous tumours have been successfully treated with surgical excision, laser therapy, liquid nitrogen cryotherapy and radiotherapy. In patients with moderately extensive cutaneous or mucosal disease and CD4+ cell counts of > or =200/ml, immunotherapy and antiretroviral drugs are indicated. Preliminary results indicate that antiretroviral therapy might be effective and well tolerated in the treatment of less advanced Kaposi's sarcoma. In patients with aggressive and extensive mucocutaneous disease or with visceral manifestations of Kaposi's sarcoma, systemic cytotoxic therapy is indicated. However, the optimal treatment has yet to be found. The combination of doxorubicin, bleomycin and vincristine (ABV) has produced high overall response rates and is indicated as first-line treatment for patients with life-threatening or visceral disease. In patients who are leucopenic and require chemotherapy, single or dual agents associated with lower myelotoxicity [i.e. bleomycin, vincristine/vinblastine or a combination of bleomycin and vincristine/vinblastine (BV)] are most widely used. Other effective cytotoxic regimens are liposomal anthracyclines, paclitaxel and vinorelbine. To date, 3 randomised trials have compared these drugs to ABV and BV. In a large phase III study, the efficacy of liposomal daunorubicin was comparable with that of ABV. In 2 phase III studies, liposomal doxorubicin was compared with ABV and BV regimens and was found to be significantly more effective in producing objective responses. Therefore, liposomal doxorubicin, although more myelosuppressive than the BV regimen, is now considered by many physicians as the first-line therapy in patients with advanced stage Kaposi's sarcoma. Paclitaxel and vinorelbine have potential in Kaposi's sarcoma, but additional studies are needed to evaluate different schedules and to compare their activity with that of the reference regimens. Institution or continuation of both effective antiretroviral therapy and prophylaxis of opportunistic infections should be recommended to all patients receiving systemic cytotoxic therapies. However, attention must be paid to the cross-toxicity and possible pharmacokinetic interactions between antiretrovirals and antineoplastics.

Acquired Immunodeficiency Syndrome↗
PubMed1988

AIDS-related Kaposi sarcoma: findings on thallium-201 scintigraphy.

No simple, noninvasive method is available for evaluating extracutaneous Kaposi sarcoma in AIDS patients or for following the tumor's response to treatment. We report our preliminary experience with thallium-201 scintigraphy in nine AIDS patients with proved Kaposi sarcoma. Eight of the nine had abnormal uptake of the radionuclide in skin, lymph nodes, oral cavity, vagina, and lungs. Only four of the nine had cutaneous Kaposi sarcoma at the time of scanning. All cutaneous and mucosal lesions were thallium avid. Two of the six patients with thallium-avid nodes underwent nodal biopsy. Both biopsies confirmed the diagnosis of Kaposi sarcoma. Cutaneous Kaposi sarcoma developed later in one of these patients, showing the efficacy of thallium scintigraphy for the early detection of extracutaneous lesions. These preliminary results show thallium avidity in Kaposi sarcoma involving the skin and various extracutaneous sites (lymph nodes, lung, mucosa, and vagina). Thallium scintigraphy is a potentially useful procedure for detecting extracutaneous Kaposi sarcoma in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Lymphangioscintigraphy in AIDS-associated Kaposi sarcoma.

Kaposi sarcoma, a common opportunistic neoplasm complicating AIDS, is thought to arise from the vasculature and possibly from lymphatic endothelium. To evaluate the nature and extent of lymphatic involvement in AIDS-associated Kaposi sarcoma, we used an improved technique of whole-body lymphangioscintigraphy. Six human-immunodeficiency-virus-seropositive men (40-51 years old) with AIDS and extensive Kaposi sarcoma had bilateral foot and/or hand intradermal injection of 0.05 ml of 99mTc-labeled human serum albumin (500 microCi, 18.5 MBq). After sequential whole-body scanning with a digital gamma camera, the findings were interpreted by comparing them with findings from similar studies in 30 other patients without AIDS or Kaposi sarcoma (26 with primary or secondary lymphedema and four with normal extremities). Unlike in normal limbs, where lymphangioscintigraphy displayed early lymphatic truncal and regional nodal filling with radionuclide, in patients with Kaposi sarcoma, lymphangioscintigraphy disclosed a variety of abnormal patterns with some features distinct and others resembling lymphatic dysplasia as seen in primary and secondary lymphedema. These included focal accumulation of tracer within lymphatic channels in the distribution of cutaneous Kaposi lesions; delayed tracer transport with absent, faint, or intense regional lymph nodal uptake; and retarded or impeded lymphatic drainage with tracer intensification in the region of Kaposi sarcoma plaques. The impaired lymphatic drainage and nodal dysfunction seen on scintigrams in patients with AIDS-associated Kaposi sarcoma suggest a close connection between the lymphatic system and this disorder.

Acquired Immunodeficiency Syndrome↗
PubMed2001

MR imaging of uterine sarcomas.

OBJECTIVE: The MR imaging appearances of uterine sarcomas are not well described in the literature. We describe the MR imaging features of uterine sarcomas. MATERIALS AND METHODS: MR images from all patients with histologically proven uterine sarcomas scanned between 1993 and 2000 were reviewed. Tumor size, its relationship to the uterus, signal characteristics, and enhancement pattern after IV injection of gadolinium were noted. RESULTS: Twenty-five scans from 22 patients were reviewed. Findings from the scans included 11 leiomyosarcomas, five mixed müllerian tumors, two rhabdosarcomas, and four endometrial stromal sarcomas. Two patterns of disease were observed, including a characteristic large heterogenous pelvic mass (n = 17) and an endometrial mass indistinguishable from endometrial carcinoma (n = 8). On T2-weighted images, the large masses were characteristically of low or intermediate background signal intensity with pockets of very high T2 signal. The areas of high T2 signal corresponded to cystic necrosis in the tumor. Pockets of high T1-weighted signal corresponded to hemorrhage. Gadolinium enhancement was present in the solid components of all tumors. This pattern was observed in all recurrent sarcomas. Some correlation was shown between the histologic subtypes and the MR imaging appearances. CONCLUSION: Uterine sarcomas show two patterns on MR imaging. The most common presentation is a large heterogenous mass. However, sarcomas can mimic endometrial carcinoma.

Adult↗
PubMed2003

Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats.

OBJECTIVE: To determine whether particular vaccine brands, other injectable medications, customary vaccination practices, or various host factors were associated with the formation of vaccine-associated sarcomas in cats. DESIGN: Prospective multicenter case-control study. ANIMALS: Cats in the United States and Canada with soft tissue sarcomas or basal cell tumors. PROCEDURE: Veterinarians submitting biopsy specimens from cats with a confirmed diagnosis of soft tissue sarcoma or basal cell tumor were contacted for patient medical history. Time window statistical analyses were used in conjunction with various assumptions about case definitions. RESULTS: No single vaccine brand or manufacturer within antigen class was found to be associated with sarcoma formation. Factors related to vaccine administration were also not associated with sarcoma development, with the possible exception of vaccine temperature prior to injection. Two injectable medications (long-acting penicillin and methyl prednisolone acetate) were administered to case cats more frequently than to control cats. CONCLUSIONS AND CLINICAL RELEVANCE: Findings do not support the hypotheses that specific brands or types of vaccine within antigen class, vaccine practices such as reuse of syringes, concomitant viral infection, history of trauma, or residence either increase or decrease the risk of vaccine-associated sarcoma formation in cats. There was evidence to suggest that certain long-acting injectable medications may also be associated with sarcoma formation.

Animals↗
PubMedDate not supplied

Microsatellite alterations in patients with thoracic sarcoma.

Few studies on sarcomas have examined the relationships between microsatellite alterations in particular loci, tumor prognosis and tumorigenesis, because sarcomas are uncommon and those prognoses can be confounded by coexisting factors, such as tumor site. We studied the relationship between microsatellite alterations and prognosis in 31 patients with thoracic sarcoma. The frequency of loss of heterozygosity (LOH) at 17p13 in stage IV sarcomas was significantly higher than that in stage I and III sarcomas (p<0.05). The 5-year survival for patients with LOH at 17p13 was significantly lower than that for patients without LOH (p<0.05). Six of 31 cases (19.4%) revealed replication error. These results suggest that p53 abnormality occurs during advanced stages of sarcoma and are related to patient prognosis, and it is possible that aberrations in mismatch repair activity are related to sarcoma tumorigenesis.

Adolescent↗
PubMed2006

Grading of soft tissue sarcomas: review and update.

CONTEXT: Histologic grading is the most important prognostic factor and the best indicator of metastatic risk in adult soft tissue sarcomas. The most commonly used systems are the French grading and the National Cancer Institute grading. Both are 3-grade systems and are mainly based on histologic type and subtype, tumor necrosis, and mitotic activity. Rules for using grading should be strictly respected and limitations of grading should be known to obtain the best performance. The most controversial point is the respective values of histologic typing and grading. Histologic typing should be clearly defined before any attempt at grading, and grading should not be used on tumors of intermediate malignancy such as atypical fibroxanthoma and on some sarcomas such as dedifferentiated liposarcoma. However, grading is useful in more than 90% of adult soft tissue sarcomas and has been adapted to pediatric nonrhabdomyosarcomatous sarcomas. Current grading is not suitable for core needle biopsies. OBJECTIVE: To review the current value and limitations of histologic grading in soft tissue sarcomas. DATA SOURCES: The reviews on grading and original studies on prognostic factors in soft tissue sarcomas were analyzed. CONCLUSIONS: Grading is the best predictor of metastasis outcome in adult soft tissue sarcomas and should be part of the pathologic report. Grading should be adapted to the modern management of patients and complemented by radiologic and molecular parameters.

Biopsy, Fine-Needle↗