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Pulmonary metastases in childhood sarcoma.

A retrospective analysis of 56 patients less than 19 years old with pulmonary metastases from previously diagnosed sarcomas was performed. Thirty patients had primary osteogenic sarcoma. Eighteen of them underwent a total of 37 thoracotomies. Overall survival was 20%. Twelve patients were noted to have metastatic Wilms' tumor, and 5 of them underwent 7 thoracotomies. This group had a 25% overall survival. Six patients had pulmonary metastases from Ewing's sarcoma. Four of these required pulmonary resection. The overall survival in these patients was 50%. The remaining 8 patients had pulmonary resection for various soft tissue malignancies, with an overll survival of 50%. The results of this review indicate a role for aggressive pulmonary resection in patients in whom the primary tumor is controlled and there is no other evidence of metastatic disease. The frequency of bilaterality and multicentric implants in patients with osteogenic sarcoma and Wilms' tumor suggest the efficacy of a median sternotomy approach in these patients.

Adolescent↗

Inhibition of chemical carcinogenesis by viral vaccines.

The incidence of 3-methylcholanthrene-induced subcutaneous tumors was significantly reduced by a single injection of inactivated type C RNA viral vaccine. Rauscher leukemia virus vaccine reduced the incidence of sarcomas from 78 to 50 percent in the BALB/cCr mouse. Radiation leukemia virus vaccine and a vaccine from a wild murine leukemia virus derived from a 3-methylcholanthrene tumor reduced the incidence of sarcoma from 86 percent to 33 and 37 percents, respectively, in the C57BL/6 mouse. These reductions in tumor incidence by virus vaccines help support the concept that type C RNA viruses serve as determinants of chemically induced cancer; additional studies of vaccines made with more purified virus preparations are necessary.

Animals↗

Immunophenotype, ras oncogenes and p53 onco-suppressor gene in benzo(a)pyrene induced malignant soft tissue tumours in Wistar rats.

This study was designed to identify the immunophenotypic characteristics of malignant soft tissue tumours, induced experimentally with benzo(a)pyrene (BaP), and to evaluate the immunohistochemical expression of the ras oncogene family and p53 onco-suppressor gene in these tumours, in association with prognostic factors. Seventy-five male Wistar rats were subcutaneous injected, dorsally, with a single dose of 10.08 mgr BaP. A solid, well-circumscribed tumour was formed at the injection site, in 70 of the animals, 80-100 days after the carcinogen's administration. The tumour as well as selected main organs were excised and studied after the animals' death. All the specimens were fixed in formalin 10%, embedded in paraffin and stained with H + E. The immunohistochemical avidin-biotin method was performed in the tumour sections, using the following monoclonal or polyclonal antibodies: vimentin, desmin, muscle specific actin (MSA), a-smooth muscle actin (SMA), myoglobin, smooth muscle myosin, a-1-antitrypsin, a-1-antichymotrypsin, S-100 protein, epithelial membrane antigen (EMA), K-ras, H-ras, Pan-ras and p53. The induced tumours of the animals were almost well-circumscribed, with a partly storiform cut surface. Histologically, their appearance was more conventional with high grade leiomyosarcomas; about half of them showed highly anaplastic areas, resembling other pleomorphic undifferentiated sarcomas. Pulmonary metastatic foci were detected in 37 animals. Immunohistochemically, all the tumours displayed positive expression of vimentin, MSA and SMA. Desmin was positively expressed in 40 tumours, smooth muscle myosin in 57 tumours and EMA in 12 tumours. All the tumours were negative for myoglobin, a-1-antitrypsin, a-1-antichymotrypsin and S-100 protein. In addition, five tumours showed a positive reaction for K-ras p21, 37 for H-ras p21, 41 for Pan-ras p21 and 14 for p53 protein. The overexpression of the oncoproteins H-ras p21 and Pan-ras p21 in these tumours was significantly associated with a non-advanced tumour stage (absence of metastatic focus). In conclusion, the histological as well as the immunophenotypic features of the induced tumours are more conventional with leiomyosarcomas mostly of high grade; many of them are "dedifferentiated". The identification of both ras and p53 gene products in these tumours indicates that alterations of these genes are common but not specific events, implicated in the tumourigenesis, which may become prognostic markers for this subtype of soft tissue sarcomas.

Animals↗

Polypoid sarcoma of the pulmonary trunk: analysis of the literature and report of a case with leptomeric organelles and ultrastructural features of rhabdomyosarcoma.

A case of polypoid sarcoma of the pulmonary trunk is described in an 80-year-old woman who had a 21-year history of episodic chest pain and hemoptysis. Ultrastructural examination revealed Z bands, characteristic of rhabdomyosarcoma, and leptomeric organelles. This is the 60th reported case of sarcoma of the pulmonary trunk. Symptoms in reported cases were variable, usually caused by tumor emboli to the lungs or by right ventricular outflow obstruction. Angiography was diagnostic. The tumor was characteristically polypoid, often multicentric, and by definition was fixed to the pulmonary trunk or valves. Non-differentiated sarcoma (often uniquely pleomorphic) was found in 37% of patients, leiomyosarcoma (once confirmed by electron microscopy) in 17%, myxosarcoma in 13%, elements of rhabdomyosarcoma in 8%, fibrosarcoma in 8%, elements of chondrosarcoma in 11%, and 5% were malignant mesenchymomas. The authors suggest that these tumors originate from the undifferentiated tissues of the bulbus cordis and propose the name myenchymoma for the tumor.

Adult↗

Use of site-specific antipeptide antibodies to perturb the serine kinase catalytic activity of p37mos.

The mos oncogene of Moloney murine sarcoma virus encodes a protein of approximately 37,000 daltons (designated p37mos). We have detected a serine protein kinase activity which is closely associated with p37mos in immune complexes obtained with antibodies [anti-mos(37-55) serum] that were generated with a peptide containing amino acids 37 through 55 of the v-mos protein (S. A. Maxwell and R. B. Arlinghaus, Virology 143:321-333, 1985). Immune complexes that were derived with antibodies generated against peptides representing the C-terminal 8 or 12 amino acids of v-mos (anti-C2 and anti-C3 serum, respectively) exhibited very little kinase activity capable of phosphorylating p37mos. Treatment of anti-mos(37-55) complexes containing active v-mos kinase with anti-C3 or anti-C2 serum resulted in a dramatic reduction of the in vitro phosphorylation of p37mos. Antiserum blocked with the appropriate C-terminal peptide had no inhibitory effect on the phosphorylation of p37mos in anti-mos(37-55) complexes which indicated that the inhibition of v-mos kinase activity was a specific effect of these antibodies. The specific inhibition of the in vitro phosphorylation of p37mos by antibodies directed against the C terminus of the v-mos protein provides strong evidence that the v-mos gene encodes a serine protein kinase. In addition, the extreme C terminus of p37mos may be critical for an active v-mos kinase.

Antibodies↗

Sarcoma and Cystosarcoma phyllodes tumors of the breast--a retrospective review of 58 cases.

A retrospective review of 58 rare breast neoplasms encountered at the British Columbia Cancer Agency between 1972 and 1992 was undertaken. There were 38 cystosarcoma phyllodes tumors, 6 carcinosarcomas, and 14 other sarcomas. Initial management involved total mastectomy in 37 cases, wide excision in 14, and excision biopsy in 7. Recurrence developed in 19 patients. Local recurrence developed in 7 patients following mastectomy, 2 incidences following wide excision, and 2 following excision biopsy. There was no significant difference in recurrence in relation to the surgical approach. Tumor grade was a significant predictor for metastatic recurrence but not for local recurrence. Adequate surgical excision remains the only curative therapy for these rare tumors. In selected cases, partial mastectomy is an acceptable treatment.

Adolescent↗

Should the number of pulmonary metastases influence the surgical decision?

OBJECTIVE: To assess, using a large homogeneous retrospective series, the prognostic value of the number of resected pulmonary metastases, and thus, to determine to what extent the number of resectable metastases should influence the surgical decision. METHODS: The survival analysis of all patients operated on for pulmonary metastases at a single center, the comparisons of 2 'histologic' groups (sarcoma and carcinoma) and, within each histologic group, of three subgroups with different numbers of resected metastases (1, 2-4, and > or = 5) were performed. The log-rank test was used to compare survival curves. RESULTS: Among 575 adult patients operated on with curative intent before December 1991, the first operation allowed the complete resection of a known number of histologically proven viable pulmonary metastases in 230 and 151 patients with metastases from carcinoma and sarcoma, respectively. The 5- and 10-year probabilities of survival (Kaplan-Meier) were 37 and 23%, respectively in carcinoma patients, and 31 and 28%, respectively in sarcoma patients (log-rank test: ns). Only the difference between patients with 1 versus 2-4 metastases from carcinoma proved statistically significant (P = 0.02), with 5-year survival estimates of 41 and 25%, respectively. Beside survival, the only significant difference between the subgroups of patients with different numbers of resected metastases was the mean interval between the diagnosis of pulmonary metastases and the resection of pulmonary metastases, which was significantly longer in patients with several metastases in both histologic groups. CONCLUSIONS: In patients with resectable pulmonary metastases from sarcoma or carcinoma, the number of metastases should have little influence on the surgical decision, except for delaying this decision in patients with several metastases until a significant interval, with or without treatment, has shown that metastatic disease remains resectable and confined to the lungs.

Adult↗

Heat shock protein 72 (HSP72), a hyperthermia-inducible immunogenic determinant on leukemic K562 and Ewing's sarcoma cells.

Following non-lethal heat stress (41.8 degrees C) and a recovery period at 37 degrees C, the inducible 72kDa HSP (HSP72) is detectable selectively on the cell surface of human Ewing's Sarcoma (ES) and of leukemic K562 cells but not on EBV transformed B cells (B-LCL) which were generated from PBL of healthy human volunteers. The HSP72 expression was measured by flowcytometric analysis using a monoclonal antibody (moAb) that specifically recognizes HSP72, the inducible form of the HSP70 group. The major histocompatibility complex (MHC) class I expression, detected with moAb W5/32 was not affected by non-lethal heat exposure and a recovery period at 37 degrees C for 12 h: ES cells express MHC class I molecules on about 80% of the cells; K562 cells exhibited no MHC class I expression neither before nor after heat shock. Inhibition of RNA-(actinomycin D) of protein-synthesis (cycloheximide) prior to heat treatment completely inhibits the expression of HSP72 on the cell surface of both tumour cells, thus indicating that de novo protein synthesis is required for HSP72 cell surface expression. Since, apart from HSP72, protein synthesis in general is down-modulated by heat shock we speculate that HSP72 molecules that are expressed on the cell surface of tumour cells might be recruited from newly synthesized proteins. The heat-inducible HSP72 cell surface expression on tumour cells could be correlated with an increased sensitivity of leukemic and sarcoma cells to lysis mediated by NK effector cells. The results of cold target inhibition assays revealed that histologically different tumour cells (sarcoma and leukemic cells) that were exposed to non-lethal temperatures have to share a similar if not identical HSP72 immunogenic determinant.

Antibodies, Monoclonal↗

Survival of pleomorphic sarcoma-37 transplanted virgin female DBA/2J mice: effects produced by high blood glucose levels alone and in combination with drugs.

Procedures for producing, monitoring, and maintaining 3-hr 400-500-mg% whole blood glucose levels in Sarcoma-37 (S-37) transplanted virgin female inbred DBA/2J mice are described. Aqueous infused 40% (w/v) dextrose was evaluated as a potential therapeutic factor. The effects of procedural variations on treatment survival and longevity are discussed. One hundred percent infusion safety and 25% increased longevity over nontreated transplanted mice were achieved. Doxorubicin and/or dacarbazine were also evaluated when administered prior to the dextrose infusion. Doxorubicin followed by intravenous dextrose increased survivor longevity by 37%, but this combination was unsafe at the drug dosages employed. A large dose of dacarbazine was safe and effective alone but unsafe when given prior to the infusion, although the survivors lived 29% longer than the untreated transplanted controls. Both drugs were marginally effective, but safe, when given together. When given together prior to the infusion, only 87% survived the treatment. The survivors lived 6 days longer than the controls.

Animals↗

Surgical treatment of pelvic sarcomas: oncologic and functional outcome.

The experiences in treating 93 consecutive patients (56 males, 37 females; mean age, 38.5 years; range, 4-69 years), including 76 patients with primary malignant bone tumors and 17 patients with soft tissue sarcomas involving the innominate bone, are reported. Oncologic and functional results were investigated in relation to the tumor stage, to the achieved surgical margin, and to the surgical procedure (hemipelvectomy, internal hemipelvectomy and endoprosthetic replacement, and continuity resection). The mean followup was 48 months (range, 8-222 months). The 5-year survival was 86% in patients with low-grade malignant bone tumors, 42% in patients with high-grade malignant bone tumors, and 25% in patients with high-grade soft tissue sarcomas. Survival was influenced by the grade of malignancy, the tumor stage, and the achieved surgical margins. Forty-six patients who survived were examined an average of 36 months after primary surgery. Excellent and good functional results were seen in 82% of patients who underwent continuity resection and in 55.5% of patients who underwent partial or total internal hemipelvectomy. All patients who survived hemipelvectomy had poor functional results. Surgical treatment of pelvic sarcomas is an extensive procedure with a considerable incidence of complications. It requires the knowledge of different techniques of resection and reconstruction of bone, joints, soft tissue, and intrapelvic organs.

Adolescent↗

Pulmonary disease at autopsy in patients with the acquired immunodeficiency syndrome.

To characterize the postmortem pulmonary disease and analyze the effectiveness of antemortem diagnosis, we examined the clinical records and autopsy material from 54 patients who died of the acquired immunodeficiency syndrome. At autopsy, all patients had pulmonary disease. One or more specific diagnoses were made in 53, including opportunistic infection, nonopportunistic infection, and Kaposi's sarcoma. Multiple postmortem pulmonary diagnoses were established in 37. Respiratory failure was the most common cause of death. Of the 97 pulmonary disorders discovered at autopsy, only 31 were diagnosed before death. The frequency with which infections were diagnosed during life varied according to the organism, and was significantly higher for Pneumocystis carinii than for cytomegalovirus or bacterial agents. Pulmonary Kaposi's sarcoma was diagnosed in only 7% of patients with autopsy documentation. The yield of diagnostic procedures also varied according to the disease present. Sputum culture was relatively effective in detecting Cryptococcus neoformans and Mycobacterium avium-intracellulare, fiber-optic bronchoscopy was extremely useful for diagnosing P Carinii, and one or more diagnoses were provided in 4 of 7 patients who underwent thoracotomy, but significant disease including cytomegalovirus infection and pulmonary Kaposi's sarcoma was frequently missed. Although the spectrum of lung disease found at autopsy is similar to that observed during life, the frequency of some pathologic processes including cytomegalovirus infection and Kaposi's sarcoma may be underrepresented in antemortem series.

Acquired Immunodeficiency Syndrome↗

The transforming protein of Moloney murine sarcoma virus is a soluble cytoplasmic protein.

The transforming gene, v-mos, of Moloney murine sarcoma virus (M-MuSV) encodes a 37,000-dalton phosphoprotein, p37mos. Since the biochemical function of this protein is unknown, we have determined the subcellular location of p37mos in M-MuSV 124-transformed cells. Using two different methods of cell lysis and fractionation, we found that newly synthesized as well as mature p37mos is a soluble cytoplasmic protein. In agreement with these results, immunofluorescent staining of cells acutely infected with M-MuSV 124, using an antiserum directed against a synthetic v-mos peptide, produced a diffuse cytoplasmic pattern. Gel filtration experiments and glycerol gradient sedimentation analysis suggest that the bulk of p37mos exists as a monomer and is not involved in a specific association with other cellular proteins. These properties of p37mos are different from those of other characterized retroviral transforming proteins.

Cell Compartmentation↗

Correlation of structure to antitumor activities of five derivatives of a beta-glucan from Poria cocos sclerotium.

A water-insoluble (1-->3)-beta-D-glucan isolated from fresh sclerotium of Poria cocos was, respectively, sulfated, carboxymethylated, methylated, hydroxyethylated, and hydroxypropylated, to afford five water-soluble derivatives. Their weight-average molecular masses (Mw) and intrinsic viscosities ([eta]) were determined by size-exclusion chromatography combined with laser light scattering (SEC-LLS), LLS, and viscometry in phosphate buffer solution (PBS) at 37 degrees C. The antitumor activities, against Sarcoma 180 tumor cell (S-180) and gastric carcinoma cell strain (MKN-45 and SGC-7901) of the native beta-glucan and the five derivatives, were tested in vitro and in vivo. The Mw values of the five derivatives in PBS were determined to be 3.8 x 10(4), 18.9 x 10(4), 16.0 x 10(4), 76.8 x 10(4), and 224.3 x 10(4), respectively. The high Mw values of the hydroxyethylated and hydroxypropylated derivatives in aqueous solution resulted from aggregation, and their true Mw values obtained in dimethyl sulfoxide were 20.1 x 10(4) and 19.1 x 10(4). The sulfated and carboxymethylated derivatives having DS of 1.0-1.3 show good water solubility, and exist as relatively expanded chains in aqueous solution. Interestingly, the native beta-glucan did not show antitumor activity, whereas the sulfated and carboxymethylated derivatives exhibit significant antitumor activities against S-180 and gastric carcinoma tumor cells. This work showed that good water solubility, relatively high chain stiffness, and moderate molecular mass of the derivatives in aqueous solution contribute beneficial to enhancement of antitumor activity.

Animals↗

Patients' understanding of words used to describe lumps: a cross-sectional study.

OBJECTIVES: To explore the interpretation of words commonly used to describe lumps. Specific words were explored to assess their understandability and implication of threat to the patient. METHODS: A cross-sectional, questionnaire-based study was undertaken. Age, gender, level of education, employment and socio-economic group were determined. The questionnaire explored the following words: malignant, tumour, carcinoma, lymphoma, sarcoma, lipoma, lymph node, nodule, ganglion, benign, cyst and gland. Participants comprised 204 consecutive adult patients attending the ENT out-patient clinic at a Bristol teaching hospital. RESULTS: Patients found 'malignant' and 'tumour' the most threatening words and were most unsure of the meaning of 'sarcoma' and 'lipoma'. Nineteen per cent (n = 37) thought a 'benign' lump was a cancer. Results did not significantly differ between demographic groups. CONCLUSIONS: A significant misunderstanding of some words commonly used to describe lumps was found. This study provides important guidance on which terms to use and which to avoid in consultations with patients.

Adolescent↗

The role of tumor size in the radiosurgical management of patients with ambiguous brain metastases.

OBJECTIVE: To identify a size cutoff below which it is safe to observe obscure brain lesions suspected of being metastases so that treatment of nonmetastases can be avoided. METHODS: Medical records from patients who underwent linear accelerator-based radiosurgery from August 1991 to October 2001 were reviewed. Inclusion criteria were defined as brain metastasis tumor volume less than 5 cm(3) (diameter, thick similar 2.1 cm) treated with a dose of 20 Gy or more. One hundred thirty-five patients had 153 evaluable brain metastases with follow-up imaging that met inclusion criteria. Median age was 54 years (range, 18-79 yr). Lesion primaries were non-small-cell lung (n = 39), melanoma (n = 44), renal (n = 37), breast (n = 18), colon (n = 3), sarcoma (n = 5), other (n = 5), and unknown primary (n = 2). Median tumor volume was 0.67 cm(3) (range, 0.06-4.58 cm(3)). The minimum peripheral dose was 20 Gy (n = 132) or 21 to 24 Gy (n = 21). At the time of analysis, the median follow-up for all patients was 10 months (range, 0.2-99 mo). RESULTS: The 1- and 2-year actuarial local control rates for all of the lesions were 69 and 46%, respectively. For lesions of 1 cm (0.5 cm(3)) or less, the corresponding local control rates were 86 and 78%, respectively, which was significantly higher than the corresponding rates of 56 and 24%, respectively, for lesions larger than 1 cm (0.5 cm(3)) (P = 0.0016). CONCLUSION: A convincing brain metastasis measuring less than 1 cm should be pursued aggressively. If the suspected brain metastasis is ambiguous, observation is proposed up to a diameter of 1 cm. This is the first study in the literature to identify a 1-cm cutoff for radiosurgical control of small brain metastases, and validation by additional studies is required.

Actuarial Analysis↗

Non-metastatic Ewing's sarcoma: twenty years of experience suggests that surgery is a prime factor for successful multimodality therapy.

Eighty-five patients (37 female, 48 male; median age 14 years) with non-metastatic Ewing's sarcoma received definitive treatment at the University of Texas M.D. Anderson Cancer Center between 1969 and 1988. Multidisciplinary therapy was administered as follows: combination chemotherapy (CC) and local radiotherapy (XRT): 65 patients; CC, XRT and surgery, 19 patients; and XRT and surgery, 1 patient. This permitted a 10-20 year follow-up for 75% of our patients. The overall survival at 5 and 10-20 years was 46.1%, and 37.2%, respectively. At 5 years, 80.5% of live patients had control of local disease. The influence of sex, age, ethnicity, primary site, size, lactic dehydrogenase (LDH) level, presence or absence of systemic symptoms, and XRT dose (<60 Gy and </=60 Gy) was analyzed and was not found to be of prognostic significance in survival. The presence of a soft tissue mass at diagnosis was found to be a significant unfavorable prognostic variable. Nine of 11 patient who underwent resection after CC and/or XRT had residual tumor in the surgical specimen. Patients who received surgery as part of the planned treatment of their primary tumor had significantly better local control and disease-free survival than those who did not undergo resection. Complications in long-term survivors are described.

Adolescent↗

Separation of effector cells mediating antibody-dependent cellular cytotoxicity (ADC) to erythrocyte targets from those mediating ADC to tumor targets.

Murine spleen cells mediate antibody-dependent cellular cytotoxicity (ADC) both to erythrocyte targets in a 51Cr release assay and to syngeneic tumor targets in a microcytotoxicity assay. The effector cells active in the two ADC assays can be separated by passage of the spleen cells through columns of Sephadex G-10 at 37 degrees C. Cells mediating ADC to sarcoma cells did not adhere to the G-10 and were recovered in the column effluent. These nonadherent cells were not cytotoxic to antibody-coated chicken red blood cells. Spleen cells which mediated ADC in a 51Cr release assay to the red cell targets adhered to G-10. Adherent effector cells could subsequently be recovered from the columns by elution with 5 X 10(-4) M EDTA.

Animals↗

Cytolytic activity of cytotoxin isolated from Indian cobra venom against experimental tumor cells.

Cytolytic activity of cytotoxin isolated from the venom of the Indian cobra (Naja naja) on experimental tumor cells was far stronger than that on normal cells such as peritoneal exudate cells, spleen cells, and erythrocytes of the rat. The effect on Yoshida sarcoma cells was temperature-dependent, being stronger at 37 degrees C than at 0 degrees C. Intramolecular disulfide linkages and free amino groups in the cytotoxin molecule were shown to be essential for the lytic action on the cell membrane. Yoshida sarcoma cells treated with 0.1 mM N-ethylmaleimide reduced the cytolytic action of the toxin. Antitumor activity of the cytotoxin toward a Yoshida sarcoma inoculated intraperitoneally into a rat was not observed.

Animals↗