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Technetium-99m-tetrofosmin scintigraphy in patients with metastatic soft tissue sarcoma.

The lipophilic cationic compound Tc-99m-tetrofosmin has been demonstrated to be a valuable tool for the detection of a variety of tumours. Tc-99m-tetrofosmin uptake by sarcomas in vitro as well as in primary tumours has been reported. Data on the visualisation of metastatic soft tissue sarcomas using this tracer are missing so far. Ten consecutive patients with histopathologically verified metastatic soft tissue sarcoma were included in the present study. Five patients had previously received cytotoxic treatment, the other five patients were chemonaive. All patients underwent whole body planar examination after administration of 500-550 MBq Tc-99m-tetrofosmin, and in case of lung metastases on CT scan, SPECT images were carried out. Non-physiological accumulation of the tracer was considered as a positive result. Scintigraphic results were compared to conventional imaging by means of MRI/CT scanning. Visualisation of distant metastases was achieved in five patients all of whom were chemonaive, while in the chemotherapeutically pretreated patient group (n=5) false negative results were seen. Progressive disease was confirmed by follow-up in all patients. Pulmonary metastases were visualised only in SPECT acquisition and not on planar images. In one patient with diffuse bone marrow infiltration (inflammatory myofibroblastic sarcoma) Tc-99m-tetrofosmin scintigraphy was positive, while CT showed a negative result. According to our results, detection of metastatic soft tissue sarcomas by Tc-99m-tetrofosmin scintigraphy was strongly dependent on the history of previous treatment of the patient. A positive finding before initiation of chemotherapy was not indicative for subsequent therapeutic response. In the staging of chemonaive patients with metastatic soft tissue sarcoma Tc-99m-tetrofosmin may provide some additional information.

Adult↗

Surgery and adjuvant radiation therapy of endometrial stromal sarcoma.

OBJECTIVE: In the treatment of endometrial stromal sarcoma, it is still not clear whether adjuvant radiation therapy improves the outcome. We wish to summarize the experiences we gathered from treating 15 patients over a period of 18 years, and to compare these to results from literature. PATIENTS AND METHODS: According to the 1989 FIGO classification for endometrial carcinoma, 11 (73%) of the 15 patients analyzed presented stage I, 1 presented stage II, and 3 presented stage III sarcoma. Of these, 11 patients (73%) had high grade stromal sarcoma and 4 had low grade stromal sarcoma. All patients were treated with surgery and adjuvant radiation therapy. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed on 11 patients (73%), vaginal hysterectomy and bilateral salpingo-oophorectomy on 2 patients, and total abdominal hysterectomy on 2 patients. Combined radiotherapy was performed on 13 patients (93%), while isolated brachytherapy and isolated external beam therapy were each performed on 1 patient. External beam therapy was administrated in daily fractions of 1.6-2.0 Gy up to a total dose of 37-57 Gy to the pelvis. RESULTS: Follow up ranged from 23 to 170 months (mean: 80 mths). 10 patients (67%) are still alive without tumor, and 5 patients have died. Of these, one died due to intercurrent disease, one due to breast-cancer, and 3 due to endometrial stromal sarcoma, presenting distant metastases within one year after therapy. Only one patient presented with an additional local recurrence. The overall actuarial survival and the disease specific survival rate was 72% and 79% respectively after 5 years, and 60% and 79% after 10 years. The overall local control rate was 93% after 5 years. There were no severe acute side effects and no late side effects. CONCLUSION: In our experience, the most effective treatment for patients with endometrial stromal sarcoma is total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant radiation therapy, due to the excellent local monitoring possibilities in all stages of disease, and a good disease specific survival in early stages.

Aged↗

The role of electron microscopy in the diagnosis of pleomorphic sarcomas of soft tissue.

Classification of pleomorphic malignancies is frequently problematic and important with regard to treatment. Their histologic differential diagnosis is extremely wide, including sarcomatoid carcinoma, melanoma, anaplastic lymphoma, and a large number of sarcomas with overlapping light microscopic appearances. Not infrequently, immunohistochemical investigations of such tumors yield conflicting or confusing results. In such cases, electron microscopy remains an invaluable investigative and diagnostic adjunct, revealing certain subcellular features that indicate a specific line of differentiation. Combining ultrastructural and immunohistochemical studies is particularly useful in these tumors. This article focuses on the ultrastructural aspects of certain sarcomas that are predominantly pleomorphic, including high-grade fibrosarcoma, myxofibrosarcoma-malignant fibrous histiocytoma, acral myxoinflammatory fibroblastic sarcoma, pleomorphic liposarcoma, pleomorphic leiomyosarcoma, and pleomorphic rhabdomyosarcoma, as well as certain sarcomas that are occasionally quite pleomorphic, including angiosarcoma, malignant granular cell tumor, alveolar soft part sarcoma, and extraskeletal osteosarcoma. We also briefly comment on the common simulators of pleomorphic sarcomas, including melanoma, carcinoma, and lymphoma.

Biomarkers, Tumor↗

[Low grade pulmonary sarcoma preceding the discovery of a uterine primary].

INTRODUCTION: Low grade pulmonary sarcomas are very rare tumours. We report the case of a low grade sarcoma of the lung occurring two years prior to the finding of a uterine primary. CASE REPORT: Complete surgical excision of a low grade pulmonary sarcoma was performed. The initial search for dissemination was negative. Two years later a follow-up scan discovered a uterine mass as well as a para-aortic shadow that proved to be the primary tumour (low grade uterine sarcoma) and a metastasis. CONCLUSION: This is the second case of a pulmonary metastasis discovered before a primary low grade uterine sarcoma. The first was found during the investigation of a pulmonary sarcoma. The main differential diagnosis to consider is metastatic leiomyosarcoma. In both cases their finding justifies the search for a uterine primary by immunohistochemical examination for oestrogen and progesterone receptors as well as pelvic ultrasound or even magnetic resonance imaging.

Aged↗

Inadvertent tumor violation during musculoskeletal sarcoma surgery and risk of recurrence.

During the limb preserving procedure for musculoskeletal sarcoma, the course of action that should be taken when a tumor or tumor-cell-contaminated adjacent tissue is violated remains controversial. From January, 1973, to July, 1989, 120 patients with musculoskeletal sarcoma were treated by limb salvage surgery and, in 40 of them, such violations inadvertently occurred during surgery. Follow-up studies on the patients have been conducted for at least one year after the violation. Soft tissue sarcoma was noted in 24 cases (low grade, 4; high grade, 20) and bone sarcoma in 16 (low grade, 6; high grade, 10). To treat the violation, re-excision with a clean margin and copious lavage was generally conducted after careful closure of the violated site. Sixteen cases in the soft tissue sarcoma group and eight in the bone sarcoma group were treated in this way. Local recurrences were found in 13 of the 40 cases (33%), but the percentage was reduced to 13 in cases treated by re-excision with a clean margin. In the present study, there was no significant effect of adjuvant therapy after violation. The survival rate in cases of local recurrence was very low, and not at all improved by adjuvant therapy.

Adolescent↗

Establishment and characterization of a new human synovial sarcoma cell line, HS-SY-II.

BACKGROUND: The line of differentiation in synovial sarcoma still remains controversial. Thus far, only a few human synovial sarcoma cell lines have been described. However, their morphologic characteristics have not been fully established. EXPERIMENTAL DESIGN: We established a new synovial sarcoma cell line (HS-SY-II) from pleural effusion with lung metastasis in a typical example of the monophasic spindle cell type. The HS-SY-II cells, in vitro and in vivo, were examined by light microscopy, immunohistochemistry, electron microscopy, and cytogenetics. RESULTS: The HS-SY-II cells showed a hypertriploid karyotype with complex chromosome abnormalities including pathognomonic t(X;18)(p11;q11), and have been stably maintained for more than 40 months in vitro, showing rather small spindle or polygonal shape without conspicuous pleomorphism. Histologic features of initially and serially transplanted tumors in nude mice were essentially the same as those of the original sarcoma, corresponding to the monophasic spindle cell variant with a prominent palisading pattern and calcified foci in parts. The HS-SY-II cells in vitro and in vivo similarly expressed vimentin and cytokeratin by immunohistochemistry, and also exhibit the same ultrastructural features such as irregularly shaped nuclei with prominent nucleoli, many paranuclearly running intermediate filaments, and filopodia-like processes. CONCLUSIONS: This HS-SY-II cell line retaining the distinct morphological characteristics as the monophasic spindle cell type of synovial sarcoma therefore will be extremely useful for various pathomorphologic investigations on synovial sarcoma.

Cytological Techniques↗

Direct and bystander killing of sarcomas by novel cytosine deaminase fusion gene.

Soft tissue and bone sarcomas of the extremities can be difficult to eradicate, and standard treatment may require limb amputation. New therapies to decrease tumor size could improve the effectiveness of treatment and decrease the frequency of limb amputation. Cytosine deaminase (CD)-based gene therapy has been shown to be effective in decreasing growth of solid tumors when animals with CD-expressing tumor cells are treated with 5 fluorocytosine (5FC), an inert prodrug that is converted to 5-fluorouracil (5FU) by CD. In this investigation, we used a novel CD-containing fusion gene to determine whether CD-based gene therapy affected soft tissue or bone sarcomas. The novel fusion gene (NGFR-CD) encodes for a protein with extracellular and transmembrane domains of human nerve growth factor receptor (NGFR) and cytoplasmic CD. Murine 2472 (2) sarcoma cells were transduced with fusion genes containing either the bacterial (NGFR-(b)CD) or yeast (NGFR-(y)CD) CD gene. 5FC treatment killed NGFR-(b)CD- and NGFR-(y)CD-transduced sarcoma cells in vitro through direct and bystander effects (P < 0.01). In contrast, 5FC treatment of mice with s.c. 2NGFR-(b)CD or 2NGFR-(y)CD tumors affected only 2NGFR-(y)CD tumors. 5FC had no effect on growth of NGFR-(b)CD tumors but caused significant decrease in the size of 2NGFR-(y)CD tumors (51 +/- 60 versus 938 +/- 767 mm(3), treated versus control, P < 0.01). Evaluation of bystander killing in vivo revealed significant tumor killing, with a 5-fold reduction in s.c. tumor volume evident in saline versus 5FC-treated mice when tumors were comprised of 90% 2472 cells and 10% 2NGFR-(y)CD selected for fluorescence-activated cell sorting (P < 0.01). Bone sarcomas were eliminated in 9 of 10 5FC-treated mice, compared with 11.8 +/- 6.0 mm(2) in saline-treated mice (P < 0.002). In addition, 5FC treatment of bone sarcomas caused a significant reduction in cancer-induced bone destruction (P < 0.002) and resulted in a reduction in the number of osteoclasts. Finally, 5FC treatment had no effect on animal weight or survival, whereas doses of 5FU providing equivalent tumor reduction as 5FC resulted in treatment-associated deaths and significant weight loss (P < 0.001).

Animals↗

Immunohistochemical evaluation of the c-kit proto-oncogene in sarcomas of the uterus: a case series.

OBJECTIVE: To evaluate the incidence of c-kit expression in uterine sarcomas. STUDY DESIGN: Immunohistochemical evaluation for expression of c-kit was performed on specimens from 11 patients with pathologically documented uterine sarcomas. Histologic subtypes included 5 carcinosarcomas, 3 leiomyosarcomas and 3 endometrial stromal sarcomas. Histologic sections of formalin-fixed, paraffin-embedded hysterectomy specimens from patients with uterine sarcomas were immunostained with c-kit (CD117) antibody. Overall staining intensity was graded as strong, intermediate or weak. RESULTS: In all 11 patients with uterine sarcoma, c-kit immunostaining was positive. Four specimens demonstrated stronger staining intensity than did the gastrointestinal stromal tumor control. Five specimens demonstrated intermediate staining intensity. Two specimens demonstrated weak staining intensity. Furthermore, in the carcinosarcoma specimens both the epithelial and sarcomatous elements were positive for c-kit staining. CONCLUSION: In this case series, c-kit expression was demonstrated in all sarcomas of the uterus regardless of histologic type. These results suggest that such drugs as imatinib mesylate, which inhibit the c-kit tyrosine kinase, should be investigated for these mesenchymal neoplasms.

Biomarkers, Tumor↗

Canine biphasic synovial sarcoma: case report and immunohistochemical characterization.

The clinical, radiological and pathologic features of a biphasic synovial sarcoma in the left elbow joint of a two-year-old male Rottweiler are presented. The tumor showed positive immunoreactivity for vimentin, Epithelial Membrane Antigen (EMA), p53 and PCNA, while it was negative for the cytokeratin used, S-100, Rb and p21. Immunohistochemistry for EMA allowed the identification of epithelioid components of synovial sarcoma, and may, therefore, contribute in establishing a diagnosis of biphasic synovial sarcoma. Intratumoral variation in PCNA immunoreactivity was minimal, indicating that the various tumor components proliferate at more or less similar rates. Overall, the characterized immunohistochemical profile for canine synovial sarcoma, not defined previously, may provide clues to the histogenesis of the phenotypically mesenchymal and epithelial elements of the tumor, and may be of value in the differential diagnosis of challenging cases, decreasing the risk of under- and mis-diagnosis. Although more cases need to be studied to determine whether there is a consistent pattern of immunostaining in canine synovial sarcoma, its potential significance is discussed in relation to the histogenesis, molecular pathology and differential diagnosis of canine synovial sarcoma.

Animals↗

High-dose ifosfamide with hematopoietic growth factor support in advanced bone and soft tissue sarcomas.

AIM: Ifosfamide and doxorubicin are the most effective agents in the treatment of sarcomas, although their contributions to survival are usually limited. High-dose ifosfamide can be used as a salvage treatment in patients with recurrent or advanced sarcoma. We evaluated efficacy and toxicity of high-dose ifosfamide in the patients with recurrent or advanced sarcoma in this study. METHODS: 39 patients with recurrent or advanced sarcoma were enrolled onto the study between 1996 and 2002. All patients had histological proven high grade sarcoma with measurable or evaluable disease. Ifosfamide was administered at the dose of 2 g/m(2) as continuous intravenous infusion for 24 h on day 1-9, in conjunction with the continuous infusion of mesna. Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor was given every cycle. The efficacy and toxicity of high dose ifosfamide (HDI) were evaluated clinically before subsequent cycle. The objective response was evaluated every two cycles. Histopathologic response was also evaluated in patients who underwent surgical resection. RESULTS: Male/female ratio was 24/15, with a median age of 20 (11-48) years. 9 patients had locally inoperable advanced disease and 30 patients had metastatic disease. 10 patients were chemo-naive. The total number of HDI-chemotherapy cycles was 103 (median 2 cycles (range, 1 to 7)). 2 patients refused the further treatment after the first cycle and 1 patient died due to neutropenic sepsis in the first cycle of treatment. 36 patients were available for the evaluation of treatment efficacy. Overall response rates were 53.8% and 90% in pre-treated patients and in chemo-naive patients, respectively. Median follow-up time was 43 months. 13 patients underwent total surgical tumor resection. Pathologic complete response was observed in 5 of 13 these patients who underwent surgery. Median progression-free survival (PFS) was 7 months (95%CI: 3.8-10.2). The median progression-free survival (PFS) were 3 and 12 months in patients who did not have tumor resection, and in those having complete tumor resection (p = 0.002). Median overall survival (OS) was 10 months (95%CI: 0.0-20) in all patients. Median OS times were 8 months in patients without tumor resection and 26.5 months in patients with those underwent surgical treatment (p = 0.0369). 2 patients who underwent surgery are still alive and disease-free. Major toxicity was myelosuppression. CONCLUSION: HDI seems to be feasible and effective in selected patients with advanced or recurrent sarcomas. Survival advantage of HDI is better when the total tumor resection can be done.

Adolescent↗

[Correlation of MR imaging features and histopathology of synovial sarcoma].

BACKGROUND & OBJECTIVE: Magnetic resonance imaging (MRI) is the best detective technique for soft tissue tumors, but it lacks specific imaging signs to distinguish various tumors. The synovial sarcoma is observed more frequently in soft tissue tumors. This study was to evaluate correlation of MRI features and histopathology of synovial sarcoma, and to improve the diagnostic accuracy of synovial sarcoma by MRI. METHODS: Twelve patients with synovial sarcomas were confirmed by operation and histopathology, included 9 men, and 3 women, aged from 35 to 50 years. Ten tumors located in lower limbs, 2 located in upper limbs. MRI was performed with a 0.5T magnet system. All images were obtained through T1-weighted imaging (T(1)WI), and T(2)-weighted imaging (T(2)WI), and some images were obtained by T(2)WI with stair. All patients received enhanced scan after Gd-DTPA injection. Radiological and histopathologic findings were compared. RESULTS: All tumors located in the places closed to joints, 2 invaded into joints, 3 invaded into bones. On T(1)WI, 12 tumors displayed signal intensity similar to that of skeletal muscle, and 3 showed cystic high intensity areas similar to that of subcutaneous fat. On T(2)WI, 6 tumors showed hyper-, iso-, and hypointense areas relative to fat constituting a triple signal intensity; 6 were multilocular, 3 were irregular, 3 were circular or elliptical. The septa configurations were seen in 5 tumors, fluid-fluid level sign was seen in 1 tumor. Maximum diameters of tumors ranged from 3 to 13 cm. All tumors enhanced asymmetrically after Gd-DTPA injection. On histological examination, 7 were poorly differentiated monophasic type, 3 were well differentiated monophasic type, 2 were biphasic type, 6 had old and/or fresh hemorrhage, 5 had large necrosis areas, 2 had calcification. CONCLUSION: MRI manifestation is specific in synovial sarcoma, and may be correlated with histopathology of synovial sarcoma.

Adult↗

Update on new diagnostic and therapeutic approaches for sarcomas.

Sarcomas represent a family of uncommon malignancies related by histopathology and developmental biology. Sarcomas arise from any of the mesodermal tissues anywhere in the body (muscles, tendons, adipose tissue, blood vessels, and joints) from cells of mesenchymal origin or in the peripheral nervous system, derived from the ectoderm. Mainly diagnosed in the extremities, sarcomas can be present also in soft tissues of the trunk, abdomen, and retroperitoneum, as well as the head and neck. During the last decade, improvements in diagnostic techniques have made it possible to identify and characterize a subset of sarcomas arising within the gastrointestinal tract known as gastrointestinal stromal tumors, which were previously commonly misclassified as leiomyosarcomas. Sarcomas are extremely heterogeneous, so expert histopathologic characterization is essential to choose the appropriate path of multidisciplinary treatment and predict possible clinical outcomes. The aim of this review is to provide a brief overview of the epidemiology, pathology, clinical presentation, and new approaches to the treatment of adult soft-tissue and bone sarcomas.

Bone Neoplasms↗

[Clinical manifestations and endoscopic characteristics of Kaposi's sarcoma in patients with acquired immunodeficiency syndrome].

BACKGROUND: Kaposi sarcoma may be the initial manifestation of immunodeficiency acquired syndrome (AIDS )in 30% of patients. The digestive tract is the thirth most affected site after the skin and lymph nodes. OBJECTIVE: To correlate the clinic and endoscopic manifestations of patients with AIDS. METHOD: 12 consecutive cases with AIDS and Kaposi sarcoma. We analyzed clinical data, positivity , immune state (leucocytes, lymphocytes, viral load, CD4 and CD8 counts, CD4/CD8 relation), opportunistic infections, tumors, endoscopic characteristics of the associated tumors, and histologic results. RESULTS: 12 patients. 11 men and 1 woman with an average age of 37.3 years old, a Karnofsky score X = 80%, weight X = 55.7 kg. All of them acquired the disease by sexual contact. The symptoms were weight loss in 6 cases, anemia in 6, abdominal pain 6, fever 6, melena 4, odynophagia 3, diarrhea 4, hematemesis 2, abdominal distention 2, dysphagia 2, bright red blood per rectum 1. The distribution of Kaposi sarcoma was as follows: hard palate 7, soft palate 2, larynx 3, esophagus 2, stomach 10, duodenum 2, colon 5 and anal conduct 1. The endoscopic appearance was in the majority a purple or blue elevated plaque that had various sizes. The biopsy was positive to Kaposi sarcoma in at least one lesion of each patient. The haemoglobin was x = 11.5, leukocytes X = 5463, total lymphocytes X = 2377 (35.7%), CD4 X = 247.8 (10.8%), CD8 X = 1008.7 (54.6%). CD4/CD8 relation = 0.20, T4/T8 = 0.25M, the viral load was X = 140,629 copies. CONCLUSIONS: The Kaposi sarcoma appears as a multiple lesion with diverse aspect and colors that go from purple to blue or red. There is correlation between a high number of Kaposi sarcoma lesions, affected organs, immunologic status and mortality.

Acquired Immunodeficiency Syndrome↗

Second cancers in long-term survivors of Ewing's sarcoma.

Previous reports suggest an increased risk of a second cancer, primarily osteosarcoma, in survivors of Ewing's sarcoma. In a retrospective review of 25 long-term irradiated survivors of Ewing's sarcoma, the incidence of second cancers was determined. The patients were free of disease for more than three years (except for one patient who developed a second cancer 2.5 years after diagnosis), with a median follow-up period of 7.6 years. All received megavoltage radiation to the primary tumor. Twenty-four of the 25 patients were treated with chemotherapy. Second cancers developed in two patients. Acute myelogenous leukemia (AML) developed in a seven-year-old 15 months after treatment. An osteosarcoma developed within an irradiated field in a 13-year-old three years after treatment. The actuarial risk of developing a second cancer at five years is 8% whereas the actuarial risk of developing a bone sarcoma is 4%. Genetic factors may play a role in the development of AML in patients with Ewing's sarcoma. Megavoltage radiation, particularly doses greater than 60 Gy, as well as alkylating agent chemotherapy may contribute to the risk for bone sarcoma. The risk of a second cancer after successful treatment of Ewing's sarcoma is similar to that expected for survivors of all childhood cancers.

Actuarial Analysis↗

Fibroblast growth factor gene expression in AIDS-Kaposi's sarcoma detected by in situ hybridization.

Biopsy samples from five acquired immune deficiency syndrome (AIDS)-Kaposi's sarcomas and one non-AIDS-associated Kaposi's sarcoma were assayed by in situ RNA hybridization onto paraformaldehyde-fixed, paraffin-embedded skin sections for the presence of two fibroblast growth factor gene transcripts, FGFB and FGF5. FGF5 gene expression was detected in the characteristic Kaposi's sarcoma spindle-shaped cells in the five samples from human immunodeficiency-positive (HIV+) patients. FGFB transcripts were detected in Kaposi's sarcoma cells as well as in epidermis of HIV- and HIV+ patients. These results complement the observations about growth factor gene expression done on Kaposi's sarcoma-derived cell lines, which thus appear to be representative of what happens in vivo. Furthermore, they demonstrate a contrasting expression pattern of FGF5 and FGFB genes, both involved in the growth factor pathogenic cascade leading to Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

A paracrine circuit in the regulation of the proliferation of macrophages infiltrating murine sarcomas.

Tumor-associated macrophages (TAM) isolated from two murine sarcomas (mFS6 and MN/MCA1) had high levels of proliferative activity (7 to 11% of cells in S phase) compared to peritoneal macrophages (1 to 2% of cells in S phase). In an effort to elucidate the mechanisms responsible for the proliferative activity of TAM, expression of c-fms and macrophage (M)-CSF was investigated in TAM and sarcoma cells. TAM had high levels of mRNA transcripts of the c-fms protooncogene, which encodes a tyrosine kinase probably identical to the M-CSF receptor, but did not express M-CSF transcripts whereas sarcoma cells had high levels of M-CSF mRNA. Sarcoma cell conditioned medium had M-CSF activity on bone marrow cells and induced proliferation of peritoneal exudate and bone marrow-derived macrophages. These activities were blocked by anti-M-CSF antibodies. These findings outline a paracrine circuit in the regulation of TAM proliferation, involving M-CSF, secreted by sarcoma cells and acting on c-fms expressing TAM. Inasmuch as TAM from these murine sarcomas have tumor growth promoting activity, a "ping pong" reciprocal feeding interaction may occur between macrophages and neoplastic cells in these tumors.

Animals↗

[Radiosensitivity of soft tissue sarcomas].

The correlation between the effectiveness of radiation therapy and the histology of soft tissue sarcomas was investigated. Of 31 cases with a soft tissue sarcoma of an extremity treated by conservative surgery and postoperative radiation of 3,000-6,000 cGy, local recurrence occurred in 12; 5 out of 7 synovial sarcomas, 4 of 9 MFH, one of 8 liposarcomas, none of 4 rhabdomyosarcomas and 2 of 3 others. As for the histological subtyping, the 31 soft tissue sarcomas were divided into spindle cell, pleomorphic cell, myxoid and round cell type, and recurrence rates were 75%, 33.3%, 16.7% and 0%, respectively. From the remarkable difference in recurrence rate, it was suggested that round cell and myxoid type of soft tissue sarcomas showed a high radiosensitivity compared to the spindle cell type with low sensitivity. Clarifying the degree of radiosensitivity is helpful in deciding on the management of limb salvage in soft tissue sarcomas of an extremity.

Adolescent↗

Cathepsin B in cells of two rat sarcomas with different rates of spontaneous metastasis.

The cysteine proteinase cathepsin B (EC 3.4.22.1) is believed to take part in biochemical processes underlying tumor metastasis. In the present study, the cellular localization, intracellular levels and extracellular release of cathepsin B activity were examined in vitro in cells of two rat sarcoma variants, LW13K2 and RPS, differing in their capacity to metastasize spontaneously to the lung of syngeneic LEW/CUB rats. The LW13K2 sarcoma metastasizes rarely, whereas the LW13K2-derived RPS variant produces a metastasis incidence of above 50%. Using fluorescent cytochemical staining, microgranular reaction centers of cathepsin B were observed in the cell cytoplasm, in some cellular processes, with apical localization in some of them, as well as at the extreme cell periphery in cells of both sarcoma variants. The appearance of this distribution of cathepsin B activity was delayed in the RPS variant. Biochemically, the intracellular level of cathepsin B activity was significantly higher in homogenates of LW13K2 cells than RPS cells. In contrast to the intracellular enzyme activity, RPS cells cultured in serum-free medium at pH 6.5 released a substantially higher amount of cathepsin B activity than LW13K2 cells into the extracellular environment; at pH 7.4 the initially higher release of cathepsin B activity from RPS cells later equalized with that from LW13K2 cells. Taken together, the results indicate that changes of pericellular pH can modulate the extracellular release of cathepsin B in both sarcoma cell variants and suggest that the rate of cathepsin B release under conditions of mildly acid pericellular pH could be related to the incidence of metastases observed in these rat sarcoma variants. Total intracellular cathepsin B activity did not exhibit positive correlation with the metastatic potential of the studied rat sarcoma variants.

Animals↗