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PubMed1986

Endocrine aspects of human uterine sarcoma: a preliminary study.

The biologic effect of estrogen and progesterone in human uterine sarcoma is poorly understood in comparison to that of endometrial adenocarcinoma. In an attempt to elucidate the endocrine status of these tumors, we have investigated the ability of these tumors to synthesize estrogen by measuring the aromatase activity and studied the effect of aromatase inhibitors on the activity. In addition, the effect of estrogen and progesterone on aromatase activity and the growth pattern of these tumors were studied in cell culture and athymic mice systems. Aromatase activities in eight uterine sarcomas ranged from 0.7 to 37 fmol/hr X mg protein, which were within the range or higher than the activity found in normal proliferative endometrium (0.5 to 3 fmol/hr X mg of protein, means = 1.6, n = 10). These results indicate that uterine sarcomas are capable of producing estrogen. However, the enzyme activity showed no correlation with the morphology of tumors or the age of patients. Results from the kinetic studies of aromatase activity in one of the uterine sarcomas indicated that 19-nortestosterone, testolactone, and aminoglutethimide (the most effective one) inhibited aromatase activity. In addition, induction of aromatase activity in two uterine sarcomas was investigated in cell cultures. Progesterone caused an eightfold increase in activity in a sarcoma that was estrogen and progesterone receptor positive but had no effect in a tumor that was estrogen and progesterone receptor negative. The growth rate of two estrogen/progesterone receptor-negative uterine sarcomas was studied in cell culture and in athymic mice. Progestin, but not estrogen, reduced the growth rate in both systems; 30 nmol/L of estrogen had no effect on the growth rate. In summary, we have found that human uterine sarcoma is able to synthesize estrogen. Progesterone is able to induce the aromatase activity in estrogen/progesterone receptor-positive tumors, and progesterone also suppresses the tumor growth rate in estrogen/progesterone receptor-negative tumors. These results suggest that a select group of uterine sarcomas is sensitive to steroid hormone and that progesterone may be potentially beneficial for therapeutic treatment of select uterine sarcomas.

Adult↗
PubMed1989

Lung resection for metastatic sarcomas: total survival from primary treatment.

The results of surgical management of 63 cases of pulmonary metastases from bone and soft tissue sarcomas, admitted at the Istituto Nazionale Tumori of Milan, between 1970 and 1987, are reviewed in this paper. To estimate the relative impact of metastasectomy on the overall performance of treatment, survival curves were calculated from the time of first thoracotomy, as well as from the initial treatment of primary sarcoma. In the present series, total actuarial survival at 10 years was 37% for osteosarcoma, 27% for soft tissue sarcomas, and 24% for the other bone sarcomas, with a median survival of 48, 56, and 36 months, respectively. Five-year survival from the first pulmonary resection was influenced by the number of metastases and the length of the first disease-free interval only in osteosarcoma, while in soft tissue sarcomas a major untoward factor was represented by local recurrence at the site of the primary tumor. These data support the concept of pulmonary metastasectomy as effective salvage therapy for radically treated sarcomas; this management can rescue a significant proportion of all relapsed patients.

Adolescent↗
PubMed1994

Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience.

PURPOSE AND METHODS: We reviewed the clinical records and pathologic findings of 37 children and adolescents with synovial sarcoma treated at our institution over a 30-year period to evaluate the prognostic significance of tumor size, invasiveness, histology, and other features. RESULTS: The 20 male and 17 female patients with synovial sarcoma had a median age of 13.7 years at diagnosis. Primary tumor sites were the extremities (n = 27), trunk (n = 8), and head and neck (n = 2). Disease stage (clinical group) was as follows: group I, n = 21; group II, n = 7; group III, n = 4; and group IV, n = 5. Nineteen patients had invasive (T2) lesions, 20 had tumors more than 5 cm in diameter, and 14 had histologic grade 3 lesions. The estimated 5-year survival rate (+/- SE) for patients with group I or II disease was 80% +/- 9%, compared with 17% +/- 15% for those with group III or IV tumors (P = .0003). An exact log-rank test, adjusted for clinical group, showed that tumor invasiveness and grade independently predicted overall and progression-free survival (P < .05); tumor size was significantly correlated with progression-free survival. A borderline significant relationship with overall survival was found for both tumor size and histologic subtype (P = .09). CONCLUSION: A controlled trial of adjuvant chemotherapy is merited in children with resected synovial sarcoma (clinical group I or II) who present with unfavorable clinicopathologic features such as large, invasive, or grade 3 lesions. Children with unresected or metastatic disease fare poorly despite multimodality therapy and require novel treatment approaches.

Adolescent↗
PubMed1998

Linkage of AIDS and cancer registries in Italy.

We report the first results of a comparison between the Italian Registry on AIDS (RAIDS) and 13 population-based cancer registries (about 8 million population in 1991) with respect to the notification of Kaposi's sarcoma and non-Hodgkin's lymphoma. Routine indicators of data quality and completeness have been found in both types of registry, consistent with the best international standards. A linkage process was carried out on about 339,000 cancer notifications and 3,134 AIDS notifications and was herein restricted to individuals under the age of 50. Out of 243 Kaposi's sarcomas at either type of registry, 90 (37%) were reported as such by both; 68% of individuals with Kaposi's sarcoma at cancer registries could be identified at the AIDS registry, including AIDS-defining illnesses other than Kaposi's sarcoma; 62% of individuals with Kaposi's sarcoma at RAIDS could be found at cancer registries. Of 2,104 non-Hodgkin's lymphomas at either type of registry, 55 were reported as such by both; 65% of individuals reported as having non-Hodgkin's lymphoma at the AIDS registry were found at cancer registries. Our present results indicate the scope for improving cancer assessment in individuals with HIV infection and AIDS and the potential of AIDS and cancer registries for such a purpose.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Periductal stromal tumor: a rare lesion with low-grade sarcomatous behavior.

Biphasic breast tumors with benign ductal elements and a sarcomatous stroma lacking a phyllodes architecture are a source of diagnostic problems, particularly because of the lack of an appropriate designation. At the Armed Forces Institute of Pathology, we have used the term "periductal stromal sarcoma" to distinguish these from phyllodes tumors. All cases coded as periductal stromal sarcoma or PDSH were retrieved from the files of the Armed Forces Institute of Pathology. Cases that fulfilled the following criteria were included in this study. The histologic features of periductal stromal sarcoma were defined as 1) a predominantly spindle cell stromal proliferation of variable cellularity and atypia around open tubules and ducts devoid of a phyllodes pattern, 2) one or more often multiple nodules separated by adipose tissue, 3) stromal mitotic activity of >/=3/10 high power fields, and 4) stromal infiltration into surrounding breast tissue. Criteria for periductal stromal hyperplasia included 1) nodular, bland stroma growing as cuffs around normal or altered ducts, 2) no to minimal atypia, and 3) at most 0-2 stromal mitotic figures per 10 high power fields. Immunohistochemistry was used to further characterize these neoplasms. Of the cases retrieved, 20 qualified as periductal stromal sarcoma and seven as periductal stromal hyperplasia. Patients with periductal stromal sarcoma ranged in age from 37 to 89 years (mean 55.3 years). The tumors measured 0.2-6.0 cm (mean 2.97 cm). Eighteen patients had excisional biopsies and two had partial mastectomies. Overall follow-up time ranged from 1 to 72 months (mean 25.3 months) with two patients (10%) showing recurrence or probable metastasis. The neoplastic cells of periductal stromal sarcoma were at least focally immunoreactive for CD34 (13 of 15), CD117 (6 of 15), less reactive for actin (HHF35, 2 of 15), and negative for estrogen and progesterone receptors. Periductal stromal sarcoma is a useful descriptive designation for generally low-grade biphasic tumors with sarcomatous stroma that do not have features of a phyllodes tumor. The development of focal phyllodes pattern in the recurrent tumor as well as development of a specific soft tissue sarcoma in one of the above cases suggest that some and possibly all periductal stromal sarcoma may evolve into a phyllodes tumor with time. Given the presence of infiltrative margins, excision with a rim of uninvolved tissue is required.

Adult↗
PubMed1995

Hemipelvectomy and intraoperative radiotherapy for bone and soft tissue sarcomas of the pelvic girdle.

Current treatment of locally advanced bone and soft tissue sarcomas of the pelvic girdle are associated with a high local and distant failure rate, and local tumor control after hemipelvectomy can be a significant problem. IORT has been used in conjunction with hemipelvectomy, both conventional (seven patients) and limb-sparing internal hemipelvectomy (one patient), in seven males and one female, median age 27 (range 24-57) years with locally extensive high grade bone (seven patients) or soft tissue (one patient) sarcomas. IORT (15-30 Gy, 8-16 MeV) was delivered to sacral resection margins and surrounding soft tissues considered likely to harbor microscopically residual disease. Four patients received 46-54 Gy postoperative radiotherapy in addition to IORT. During a median follow-up of 33 months (range 6-131 months) two patients developed a local recurrence (25%), and five patients distant metastases (62%). Three patients with pelvic girdle sarcomas remained free of tumor (37%) with a mean follow-up of 100 (range 49-131) months. There was no treatment-related mortality. Two patients developed radiation-induced necrosis of the coccyx (25%). On the basis of this preliminary experience, it appears that IORT may substantially help to control local recurrence and survival in patients with marginally resectable sarcomas of the pelvic girdle after hemipelvectomy. Since the majority of the patients die from metastatic disease, there is a need for adjuvant systemic treatment.

Adult↗
PubMed1996

Reverse transcriptase-polymerase chain reaction amplification of MDR1 gene expression in adult soft tissue sarcomas.

Expression of the multidrug resistance gene MDR1 is reported to be an important determinant of the response to chemotherapy and survival in some cancers. We compared three methods for determining the intrinsic MDR1 expression in soft tissue sarcomas. We studied MDR1 gene expression in 39 samples from 33 cases of soft tissue sarcomas comprising 11 liposarcomas, nine malignant fibrous histiocytomas, six leiomyosarcomas, four malignant schwannomas, three fibrosarcomas, three synovial sarcomas, and three epithelioid sarcomas, and seven cases of benign soft tissue tumors in adult patients. To detect MDR1 mRNA, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed in all samples. Furthermore, RNA dot-blot analysis with digoxigenin-labeled RNA probe and immunohistochemistry with JSB-1 and C-219 antibodies for P-glycoprotein were employed in 34 and 37 samples in soft tissue sarcomas, respectively. We compared these three detection techniques. Of the 39 specimens, 18 (46%) showed MDR1 PCR products. Liposarcomas (six of 11), malignant fibrous histiocytomas (six of nine), leiomyosarcomas (four of six), fibrosarcomas (two of three) revealed high or intermediate MDR1 expression at high frequency. No MDR1 expression was detectable in malignant schwannomas, synovial sarcomas, or epithelioid sarcomas. Of seven benign soft tissue tumors, one ganglioneuroma and one lipomatosis showed low levels of MDR1 expression. By RNA dot-blot analysis, MDR1 transcripts were detectable in 12 of 34 specimens (35%). Four samples were negative by dot blot despite positivity with RT-PCR. Concordance between MDR1 expression by RNA level with RT-PCR and dot blot and at the protein level with immunohistochemistry using C-219 was found in 16 (47%) of the 34 comparable specimens. Eight samples showed positive immunoreactivity for C-219 despite negative results in RT-PCR and dot-blot analysis. The intrinsic MDR1 expression in soft tissue sarcoma seemed to depend on certain tumor types, such as liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and fibrosarcoma. For the evaluation of MDR1 expression, RT-PCR is useful because of its relative simplicity and sensitivity. However, the clinical significance of such low levels of MDR1 expression detected only by RT-PCR must be discussed within systematically treated patient groups.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Postirradiation sarcomas. A single-institution study and review of the literature.

BACKGROUND: With improvement in survival after cancer treatment, it is becoming increasingly important to examine treatment-related morbidity and mortality. Sarcomas can develop in the irradiated field after radiation therapy (RT). The authors undertook a study to estimate the risk, and compared the risk of postirradiation sarcoma (PIS) with other treatment modalities used against cancer. METHODS: Since 1987 the authors have reviewed the records of 1089 patients with head and neck, gynecologic, gastrointestinal, and extremity sarcomas. Of these 1089 patients, 37 had a prior history of RT. RESULTS: Conditions for which these patients received RT included: Hodgkin's disease (2 patients), retinoblastoma (3), non-Hodgkin's lymphoma (2), acne (1), astrocytoma (1), multiple recurrent mixed parotid tumor (1), laryngeal cancer (1), papillary adenocarcinoma of the thyroid (1), bony fibrous dysplasia (1), lymphangioma (1), squamous cell carcinoma of the nasopharynx (1), Ewing's sarcoma (1), choriocarcinoma (1), menorrhagia (4), cervical cancer (6), ovarian cancer (2), breast cancer (7), and hypoplasia (1). RT doses ranged from 3000 to 12,440 cGy. Latency time from RT to the development of PIS averaged 12 years. More than 15,000 patients have received RT for various conditions at our institution since 1955. CONCLUSIONS: From our data and a review of the literature, we estimate the risk of PIS with long-term follow-up to be 0.03-0.8%. From a review of the literature that compared mortality risks of chemotherapy, general surgery, and anesthesia, the risk of PIS appears no worse. Thus, given the large number of patients who can be cured or receive palliative treatment with RT, concern regarding PIS should not be a major factor influencing treatment decisions in patients with cancer.

Adolescent↗
PubMed1987

Kaposi's sarcoma and acquired immunodeficiency syndrome. Postmortem findings in twenty-four cases.

Autopsy results on twenty-four patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma were reviewed. At postmortem, 29% of patients had evidence of visceral Kaposi's sarcoma without skin lesions. The most common sites for visceral involvement with Kaposi's sarcoma were as follows: lung (37%), gastrointestinal tract (50%), and lymph nodes (50%). At the time of death, only 25% of patients had evidence of cutaneous disease alone. The patients survived up to 36 months after the diagnosis of AIDS was made according to the specific diagnostic criteria established by the Centers for Disease Control. Many of the patients had severe, disseminated infections during the course of their AIDS illness. The most common infections diagnosed during the patients' clinical courses and/or at autopsy were cytomegalovirus (75%), candidiasis (50%), Mycobacterium avium intracellulare (50%), Pneumocystis carinii pneumonia (50%), bacterial pneumonia (33%), and herpes simplex virus (29%). Nearly 80% of the deaths were attributed to infection. In only one case was overwhelming Kaposi's sarcoma determined to be the cause of death.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Treatment of uterine sarcoma at the University of Florence from 1980-2001.

PURPOSE: To correlate the treatment used in uterine sarcoma with outcome. The prognostic importance of pathology, clinical parameters and treatment are analyzed. PATIENTS AND METHODS: Forty patients (median age, 59 years; range, 37-85) with histologically verified uterine sarcoma were identified from a database compiled at the University of Florence from 1980 to 2001. Patients were followed for a median of 54 months (range, 3 months to 10 years). Twenty-four patients had leiomyosarcoma, 12 patients had mixed mullerian tumors, and 3 patients had endometrial stromal sarcoma. Stage I, II, III and IV tumors were identified in 22, 2, 9 and 7 patients, respectively. High, intermediate, low and unspecified grade sarcoma occurred in 9, 4, 5 and 22 patients, respectively. RESULTS: At the time of analysis, 58% of patients had died and 42% were alive, with a median survival of 2 years from the initial diagnosis. Cause-specific survival for the entire group was 81%, 41% and 25% at 1, 3 and 5 years, respectively. In our series, univariate analysis for cause-specific survival did not demonstrate statistical significance for histology, grade, stage or age. There appeared to be a significant impact for postoperative radiotherapy in reducing local recurrence with a total dose higher than 50 Gy. CONCLUSIONS: Our data favor treatment for uterine sarcoma with radical surgery plus irradiation, even in elderly patients.

Adult↗
PubMed2005

Immunohistochemical analysis of a muscle ankyrin-repeat protein, Arpp, in paraffin-embedded tumors: evaluation of Arpp as a tumor marker for rhabdomyosarcoma.

Arpp, a protein including an ankyrin-repeat, P EST motif, and p roline-rich region, is a recently identified protein that is exclusively expressed in striated muscles. This study comprehensively analyzed its expression among soft tissue sarcomas of various histological types and evaluated its potential use for the differential diagnosis of rhabdomyosarcoma (RMS). Formalin-fixed, paraffin-embedded tissues, including 37 RMS cases, 88 non-RMS sarcomas, and 38 carcinomas, were analyzed for Arpp expression. Arpp was detected in 33 (89.2%) of 37 RMS cases by immunohistochemistry. Western blot analysis revealed expression of Arpp in all RMS cases tested. High expression of Arpp was generally associated with morphological evidence of skeletal muscle differentiation of tumor cells. In contrast, Arpp displayed 6.3% (8/126) positivity among the non-RMS tumors. Focal or weak expression was seen in malignant fibrous histiocytoma (2/27), synovial sarcoma (1/11), Ewing sarcoma (1/5), and epithelioid sarcoma (3/5), whereas one epithelioid sarcoma displayed strong expression for Arpp. A comparative analysis of the Arpp profile with that of myogenic markers in RMS revealed that the sensitivity of Arpp (89.2%) was higher than that of myoglobin (59.6%) and comparable with that of myogenin (88.2%), MyoD (80.6%), muscle-specific actin (83.8%), and desmin (89.2%). These results suggested that Arpp is sensitive to and specific for RMS. Thus, we proposed that Arpp is a novel skeletal muscle-specific marker, which is useful for differential diagnosis of RMS.

Biomarkers, Tumor↗
PubMed1981

[A case of alveolar soft-part sarcoma with lung and cerebral metastasis (author's transl)].

A 37-year-old housewife who had episodes of surgical removal for an alveolar soft-part sarcoma of her right leg 15 years ago, and total removal for right lung metastasis 2 years ago, was admitted to our service with complaints of headache, vomiting, dyscalculia and recent memory disturbance which started about 4 months prior to admission. Neurological examination revealed papilledema and disorientation. Left carotid angiography and CT scan showed a ball-like vascular tumor in the left frontal lobe. Presumptive diagnosis of metastatic brain tumor in the left frontal lobe was made in our service. Left fronto-parietal craniotomy was carried out on Feb. 22, 1977 and total removal for the metastatic tumor were made. Specimens of the tumor showed typical feature of alveolar soft-part sarcoma histologically. Postoperative course was well and she was discharged without neurological deficits. Two years after the previous surgery for cerebral metastasis, another metastatic tumor was found in the left frontal lobe again. Total removal for this solitary metastatic tumor was performed again. Histological and electron microscopical examination was made with this tumor specimen. Typical feature of alveolar soft-part sarcoma was confirmed. She was discharged with a marked improvement of her symptoms. At present, it has been passed about a year after the second surgery on her, she is doing well without neurological deficits. Clinical features of alveolar soft-part sarcoma were discussed, especially with the comparison of clinical feature between the reported cases of Japan and the cases of foreign countries. Regarding the choice of the treatment of this tumor, total removal was seemed to be the best management. Therefore, all efforts should be focussed to discover in the earlier stage of this tumor.

Adult↗
PubMed1982

Alimentary tract involvement in Kaposi sarcoma: radiographic and endoscopic findings in 25 homosexual men.

An outbreak of Kaposi sarcoma has recently occurred among young homosexual men. It differs from the classic form in its virulence and preponderance of systemic manifestations. Twenty-five homosexual men with a mean age of 37 and biopsy-proven Kaposi sarcoma received extensive gastrointestinal evaluations. Twelve patients (48%) had evidence of gastrointestinal involvement by radiography and/or endoscopy. Lesions were found in the larynx, oropharynx, esophagus, stomach, duodenum, and colon. Radiographically they ranged from minimally elevated submucosal lesions, some with central ulceration, to polypoid defects. Abdominal CT was obtained in 18 patients, 11 of whom showed abnormalities. Of those with abnormal CT, 50% had retroperitoneal adenopathy. The gastrointestinal radiographic findings with endoscopic correlation in this unusual group of patients is discussed.

Adult↗
PubMed1988

Combination chemotherapy and alpha-interferon in the treatment of Kaposi's sarcoma associated with acquired immune deficiency syndrome.

Thirteen men with a median age of 37 (range 28 to 46) years who had extensive Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS) were treated with combination chemotherapy and alpha-interferon. Four patients had stage III disease and nine had stage IV disease (one with pulmonary and eight with gastrointestinal involvement). Treatment consisted of monthly courses of actinomycin D, 1 mg/m2, and vinblastine sulfate, 6 mg/m2, given intravenously on day 1, bleomycin, 10 mg/m2 given intravenously on days 1 and 8, and human lymphoblastoid (alpha-) interferon, 10 million U/m2 given subcutaneously three times a week for six doses starting on day 14. Forty-one treatment cycles (median 3, range 1 to 12) were administered. The median granulocyte and platelet counts on day 14 before the start of interferon therapy were 600 X 10(9)/L and 134 X 10(9)/L respectively; the counts did not fall further during interferon therapy. There was no difference in T-cell subsets, 2',5'-oligoadenylate synthetase level or results of blastogenesis studies after interferon therapy. Four patients required admission to hospital for neutropenia-associated fever. A complete response (of 24 weeks' duration) was seen in one patient and a partial response (of 14 to 44 weeks' duration) in four. One patient had a mixed response, with regression of skin involvement but progression of pulmonary disease. The median length of survival was 48 (range 4 to 143) weeks. Eleven patients died of progressive Kaposi's sarcoma, one of lymphoma and one of Pneumocystis carinii pneumonia. The results suggest that this form of therapy is not appropriate for patients with Kaposi's sarcoma associated with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Evaluation of sequential thallium and gallium scans of the chest in AIDS patients.

UNLABELLED: With decreasing incidence of pneumocystis carinii pneumonia (PCP) in AIDS as a result of prophylactic regimens, there is a higher incidence of tuberculosis (TB), mycobacterium avii complex (MAC), kaposi sarcoma and malignant lymphoma. There is a need for differentiating these various pathological entities. The purpose of this study was for a retrospective evaluation of sequential thallium and gallium scans in AIDS patients for differentiating intrathoracic kaposi sarcoma from malignant lymphoma and opportunistic infections. METHODS: A total of 181 patients had both studies completed between March 1992 and May 1994. The final diagnosis was verified only in 83 patients. Results were correlated with the CD4 counts, bronchoscopic and chest radiograph findings. RESULTS: In patients with pulmonary kaposi sarcoma and no opportunistic infections (19 patients), a thallium-positive, gallium-negative pattern was detected in 17 patients with a sensitivity of 89%. In the presence of kaposi sarcoma plus opportunistic infections, this pattern was only detected in 7 of 19 patients (sensitivity dropped to 37%). In 45 patients with opportunistic infections and no kaposi sarcoma, only two false-positive findings were found in patients with cytomegalic virus pneumonia for a specificity of 96%. For the whole group of 83 patients, sensitivity was 63%; specificity 95%; positive predictive value 92%; accuracy 81%; and negative predictive value 75%. CONCLUSION: A thallium-positive, gallium-negative pattern in AIDS patients has a high specificity for the diagnosis of kaposi sarcoma, however, the sensitivity dropped from 89% to 37% in the presence of opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed1986

Modification of tumor cell sensitivity to antineoplastic agents lonidamine and bouvardin (NSC 259968) at elevated temperatures.

Lymphocytic leukemia P388 and Sarcoma-180 cells were exposed to various concentrations (0.01 mM to 0.04 mM) of lonidamine at 37 degrees C and 43 degrees C for 30 min and 60 min in vitro. Similarly combined effect of lonidamine and bouvardin on these tumor cells was also assessed at 37 degrees C and 43 degrees C. The effect was evaluated by comparing the rate of 3H-thymidine incorporation in treated cells to that of control cells. It was observed that at 37 degrees C lonidamine did not exert cytotoxic effect on P388 cells at prescribed time interval. Sarcoma-180 cells, however, showed significant sensitivity to the drug at 37 degrees C. Lonidamine exhibited greater cytotoxicity at 43 degrees C towards both P388 and Sarcoma-180 cells at 30 and 60 min exposure. Lonidamine also enhanced cytotoxicity of bouvardin in P388 and reversed the natural resistance of Sarcoma-180 cells to bouvardin at 37 degrees C.

Animals↗
PubMed1985

Serine kinase activity associated with Maloney murine sarcoma virus-124-encoded p37mos.

An antiserum directed against amino acid residues 37-55 [anti-mos (37-55) serum] of the predicted v-mos sequence was used to precipitate p37mos from Moloney murine sarcoma virus-124 (Mo-MuSV-124) acutely infected 3T3 cells. Proteins with sizes ranging from p37mos to 43 kDa (p43) were found to be phosphorylated when anti-mos (37-55) immune complexes containing p37mos were incubated with [gamma-32P]ATP and Mn2+. The phosphorylation of p37mos and p43 could be specifically blocked when the anti-mos (37-55) serum was incubated with 37-55 cyclic mos peptide prior to immunoprecipitation, but not if the serum was preincubated with an unrelated peptide representing amino acids of the myc protein sequence. Anti-mos (37-55) immune complexes from uninfected 3T3 cells did not produce any phosphorylated proteins the size of p37mos or p43. However, a 50-kDa protein (p50) was phosphorylated in both unblocked and mos peptide-blocked anti-mos (37-55) immune complexes from infected 3T3 cells, and in immune complexes from uninfected cells. Quercetin, an inhibitor of some protein kinases, inhibited the kinase phosphorylating p50 but not the kinase phosphorylating p37mos and p43. Preabsorption of the cell extract prior to immunoprecipitation with an excess of formalin-fixed Staphylococcus aureus, complexed with preimmune normal rabbit serum IgG, specifically removed the kinase phosphorylating p50. The amount of in vitro phosphorylated p37mos and p43 in the immune-complex kinase assay reached a maximum in extracts of 3T3 cells 2-3 days postinfection with Mo-MuSV 124 but decreased to trace levels after 5 days. Metabolically and in vitro phosphorylated p37mos generated an identical pattern of phosphopeptides upon partial V8 protease digestion. Based on peptide mapping and a kinetic analysis of the in vitro phosphorylation reaction, p37mos appears to be a precursor to the p43 phosphorylated species. Phosphoamino acid analyses revealed only phosphoserine in in vitro phosphorylated p37mos and p43mos. It was concluded that p37mos is closely associated with a serine kinase activity and that the in vitro phosphorylation of p37mos may lead to formation of a highly modified mos protein (p43) by way of superphosphorylation.

Animals↗