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PubMed1998

Detection of chromosomal aberrations in tumor cells and tumor infiltrating lymphocytes by molecular cytogenetics in patients with gynecological cancer.

Conventional cytogenetic studies of tumor cells from patients with breast or ovarian cancer have shown multiple chromosomal abnormalities including chromosomes 7, 12, and 17. This study was designed to analyze the cytogenetic features of tumor cells and tumor infiltrating lymphocytes (TILs) by using a combination of magnetic activated cell sorting (MACS) and fluorescence in situ hybridization (FISH). Tumor cell, peripheral blood (PB), and TIL samples from 37 patients (20 ovarian tumors, 13 breast cancers, 3 uterine sarcoma, 1 carcinoma of the filamentary tube) were analyzed for the presence of numerical aberrations of chromosomes 7, 12, and 17. All of the tumor cells showed a high frequency of numerical aberrations of chromosomes 7, 12, and 17, especially trisomies or tetrasomies. There was no statistically significant difference in the incidence of chromosomal abnormalities in tumor tissue and effusions, or between primary and relapsed disease in patients with breast or ovarian tumors. However, tumor cells from patients with solid metastatic disease had significantly higher numbers of aberrations of chromosome 7 in the primary tumor than in tumors from patients without metastases (P = 0.049), suggesting that chromosome 7 is frequently involved in the progression of disease. Monosomies and trisomies of chromosomes 7 and 12 also occurred at a low percentage of TILs without any statistically significant difference between primary and relapsed tumors. The presence of these aneuploidies might be responsible for treatment failures in the immunotherapy of gynecological cancer.

Adult↗
PubMed1995

Viral interleukin 10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors.

After the cloning of murine cytokine synthesis inhibitory factor, it was recognized that a homologous open reading frame was encoded within the Epstein-Barr virus (human herpes virus 4). This viral protein has now been termed viral interleukin 10 (vIL-10) to reflect its protein sequence homology to "cellular" IL-10 (cIL-10, either murine or human IL-10). It is now widely accepted that vIL-10 shares many functions with cIL-10, principally, the ability to enhance survival of newly infected B cells and to diminish the production of IFN-gamma and IL-2 during ongoing immune reactions. The immunomodulatory effect of locally secreted vIL-10 and murine IL-10 (mIL-10) was examined in tumor models using CL8-1 (a BL6 melanoma cell line transfected with the H-2Kb class I gene) in syngeneic animals. Although parental BL6 tumor cells grow in immunocompetent syngeneic hosts, CL8-1 are rejected. To achieve local secretion of vIL-10, we generated vIL-10 retroviral vectors. While nontransduced CL8-1 cells (1 x 10(4)) failed to grow when injected intradermally in C57BL/6 mice, CL8-1 cells (1 x 10(4)) transduced with vIL-10 formed palpable tumors and eventually killed 80% of injected animals. Suppression of tumor rejection was also noted when CL8-1 tumors with or without vIL-10 transfection were admixed with syngeneic vIL-10-transfected fibroblasts and inoculated. Since the in vitro proliferation of the tumor was not altered after transduction with the vIL-10 gene and injection of vIL-10-transduced CL8-1 does not affect the rejection of nontransduced CL8-1 inoculated at a distant site, local vIL-10 secretion appears to suppress the process of immune rejection of the target cells in a dose-dependent manner. Similar results were observed for the H-2b MCA105 sarcoma tumor model in allogeneic BALB/c mice (H-2d). Although all animals that received nontransfected MCA105 rapidly rejected these tumors, MCA105 sarcomas transfected with vIL-10 remained palpable for up to 37 d. The local immunosuppressive effect of gene-delivered vIL-10 could be neutralized by anti-human IL-10 monoclonal antibody or could be reversed by the systemic administration of IL-2 or IL-12. In marked contrast, mIL-10 transfection of CL8-1 significantly suppressed tumor growth and frequently led to the rejection of tumor. Similar results were obtained for the murine tumor cell lines MCA102.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

CT of hypervascular hepatic tumors: are unenhanced scans necessary for diagnosis?

OBJECTIVE: In most institutions, a combination of unenhanced and contrast-enhanced CT is used to screen patients for suspected hypervascular hepatic neoplasms. Elimination of the unenhanced examination could save time and expense and reduce the patient's exposure to radiation. We compared unenhanced and incremental bolus dynamic contrast-enhanced CT for detection of hypervascular hepatic neoplasms and evaluated the need for preliminary unenhanced hepatic CT. SUBJECTS AND METHODS: We prospectively examined 101 consecutive patients with hypervascular primary hepatic malignant tumors or suspected hypervascular metastases. Primary hepatic neoplasms included hepatocellular carcinoma (seven), sarcoma (two), and hemangioendothelioma (one); extrahepatic primary tumors included breast (37) and renal cell (24) carcinoma, melanoma (15), carcinoid (nine), and endocrine and other tumors (six). All patients had both unenhanced and bolus dynamic contrast-enhanced CT with 5-mm collimated sections at 8-mm intervals. For contrast-enhanced CT, 150-180 ml of IV contrast material, a mechanical power injector, and a scanning protocol that allowed completion of liver imaging within 2 min were used. Both unenhanced and contrast-enhanced CT scans were compared for detection and conspicuousness of hepatic lesions. RESULTS: Hepatic lesions were found in 34 patients. In 21 patients, all hepatic lesions seen on unenhanced scans also were apparent on contrast-enhanced scans. However, in 12 (57%) of 21 patients, lesions were more conspicuous and better defined on contrast-enhanced scans. The absolute number of lesions detected with each method of scanning differed in 12 patients. In four patients, the contrast-enhanced scan showed more lesions; in five patients, the unenhanced scan showed more lesions; and in three patients, administration of contrast material obscured some lesions shown on unenhanced scans and made others more conspicuous. If only a contrast-enhanced CT scan had been obtained, the presence of malignant hepatic neoplasm would have been missed in only one case (a patient with a single 2.8-cm metastasis from renal cell carcinoma). CONCLUSION: Bolus dynamic contrast-enhanced CT alone correctly showed the presence or absence of primary or metastatic hypervascular hepatic tumors in 100 of 101 cases. If the goal of CT examination is detection of hypervascular hepatic lesions, use of contrast-enhanced CT alone may be adequate and the addition of unenhanced scans is not cost-effective.

Adult↗
PubMed2002

Altered expression of G1 regulatory proteins in human soft tissue sarcomas.

CONTEXT: Soft tissue sarcomas constitute a heterogeneous group of tumors for which tumorigenesis is not fully understood. Altered cell-cycle regulation may underlie the development and/or progression of human malignancies. However, data concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are very limited. OBJECTIVES: To detect the abnormal features of cell-cycle regulatory proteins in soft tissue sarcomas and to determine the potential role of these proteins in clinical behavior. DESIGN: The p53 and Rb-cyclin D pathways were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin D1, and cdk4 proteins, respectively. RESULTS: Of the 67 sarcomas analyzed, nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated with tumor grade. Abnormalities involving the Rb-cyclin D pathway were identified in all of the tumors by the altered expression of either pRb (72%) or p16 (94%). Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression, respectively. Overexpression of cyclin D1 showed an association with pRb and p53. There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or relapse. CONCLUSION: Disturbance in the cell-cycle regulatory system involving the p53 pathway and the Rb-cyclin D pathway is relatively frequent in soft tissue sarcomas and may be a contributing factor in the tumorigenesis of these tumors. The alterations in the Rb-cyclin D pathway probably constitute an early event, whereas the abnormalities in the p53 pathway seem to be involved in tumor progression. It is noteworthy that cyclin D1 may play a key role in linking both pathways.

Cell Cycle Proteins↗
PubMed1986

Sarcomas of the uterus: a clinicopathologic study of 119 patients.

This series consists of 119 uterine sarcoma patients treated at the University of Helsinki Central Hospital during the 20-year period of 1958 to 1977. It comprises the three main histologic varieties: leiomyosarcomas, 51 patients; mixed müllerian sarcomas, 45 patients; and endometrial stromal sarcomas, 23 patients. The clinicopathological features that could have had a bearing on prognosis were examined retrospectively. The clinical stage at the time of primary treatment was the main prognostic factor. Other important factors were the degree of histologic differentiation and the mitotic activity. The overall five-year survival rate for patients with leiomyosarcomas was 39%; for mixed müllerian sarcomas, 33%; and for endometrial stromal sarcomas, 61%. The ten-year survival figures were 27, 14, and 37%, respectively. Some features of the diagnosis, the natural history, and the different methods of treatment of these diseases are discussed.

Adult↗
PubMed1997

Ewing's sarcoma and primitive neuroectodermal tumor in adults: are they different from Ewing's sarcoma and primitive neuroectodermal tumor in children?

PURPOSE: To determine whether age at diagnosis influences the behavior of Ewing's sarcoma and primitive neuroectodermal tumor (PNET). PATIENTS AND METHODS: We reviewed the clinical features, treatment, and outcome of 59 consecutive patients with Ewing's sarcoma and PNET treated on the Adult Sarcoma Unit at our institution from 1980 to 1995. RESULTS: The 37 male and 22 female patients had a median age of 24 years. Lower limb was the most common primary tumor site. Fifteen patients had nonmetastatic tumor less than 100-mL volume, 27 had nonmetastatic disease greater than 100-mL volume, and 17 had evidence of metastatic disease at presentation. The origin of the primary tumor was soft tissue in 28 cases, bone in 30, and uncertain in one. The Kaplan-Meier estimate of 5-year overall survival (OS) in all patients was 38% and of progression-free survival (PFS), 27%. When patients with metastatic disease at presentation were excluded, these figures increased to 52% and 34%, respectively. Bulk of disease at presentation and response to primary treatment were statistically highly significant predictors of both PFS and OS. Age and tissue of origin of the tumor did not influence outcome. CONCLUSION: The behavior of Ewing's sarcoma and PNET in adults is no different from its behavior in children. We feel the way forward in the treatment of adults with Ewing's sarcoma and PNET is for them to be included in the current multicenter trials of multidisciplinary treatment directed at children.

Adolescent↗
PubMed1985

Alveolar soft part sarcoma of the uterine cervix.

Alveolar soft part sarcoma is a histologically distinctive neoplasm of uncertain histogenesis. Since its initial description in 1952, more than 200 cases have been reported. The extremities are most often the sites of involvement; the tongue, bones, and the orbit have been less commonly involved. The present paper describes a case of alveolar soft part sarcoma which was present only within the uterine cervix of a 37-year-old woman. Histologically, the tumor cells were arranged in the characteristic alveolar pattern; diagnostic PAS-positive diastase-resistant needle-shaped crystals were observed within the cytoplasm of the tumor cells. After the initial biopsy, the patient underwent a radical hysterectomy and pelvic lymph node dissection. Although no residual tumor was found within the cervix, a microscopic focus of tumor was detected in an obturator lymph node. The patient is at present clinically free of disease.

Adult↗
PubMed1986

Antitumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: successful immunotherapy of established pulmonary metastases from weakly immunogenic and nonimmunogenic murine tumors of three district histological types.

We have recently shown that the systemic administration of lymphokine activated killer cells (LAK cells) plus relatively low doses of recombinant interleukin 2 (RIL-2) or the administration of high doses of RIL-2 alone can reduce the number of established pulmonary metastases from the weakly immunogenic MCA-105 sarcoma in mice. We have now analyzed the therapeutic efficacy of these treatments on both weakly and nonimmunogenic tumors of three distinct histological types in two different mouse strains. In all experiments, LAK cells were administered i.v. on days 3 and 6 and RIL-2 was injected i.p. from days 3 through 8 after tumor induction. The MCA-101 sarcoma was completely nonimmunogenic as defined by its inability to successfully immunize C57BL/6 mice. Nevertheless, administration of LAK cells plus 7,500-10,000 units RIL-2 was highly effective in reducing the number of established 3-day pulmonary metastases from this sarcoma [at 7,500 units RIL-2, mean number of metastases 37 +/- 11 (SE); P less than 0.05; at 100,000 units, 2 +/- 1; P less than 0.05] when compared to Hanks' balanced salt solution treated control animals (116 +/- 9). Likewise, RIL-2 alone at doses of 20,000 units/injection or greater had significant antimetastatic effects (77 +/- 12; P less than 0.05). Established 3-day pulmonary metastases from the MCA-38 adenocarcinoma in C57BL/6 mice and the M-3 melanoma in C3H mice were also susceptible to adoptive immunotherapy with LAK cells plus RIL-2 and with high dose RIL-2 alone. Treatment of mice with LAK cells alone or with low doses of RIL-2 alone (less than or equal to 20,000 units/injection) had little if any antitumor effects. LAK cells were tested for cytolytic activity in vitro against tumor target cells of a variety of histological types; there was no discernible relationship between susceptibility to lysis by LAK cells in vitro and therapeutic efficacy in vivo. These findings have thus demonstrated that the successful immunotherapy of established pulmonary metastases with LAK cells plus RIL-2 or with high dose RIL-2 alone includes: tumors that are immunogenic and nonimmunogenic; tumors of distinct histological types such as sarcoma, adenocarcinoma, and melanoma; and tumors in at least two different mouse strains, C57BL/6 and C3H, and that there is little correlation between the in vitro lysability of tumor cells by LAK effectors and the susceptibility of these same tumors to successful immunotherapy in vivo.

Animals↗
PubMed1993

Mycoplasma penetrans infection in male homosexuals with AIDS: high seroprevalence and association with Kaposi's sarcoma.

Antibodies to Mycoplasma penetrans were found at an unusually high frequency in male homosexuals with AIDS (55 of 149; 37%) and in human immunodeficiency virus (HIV)-infected asymptomatic homosexuals (13 of 49; 26.5%) but not in intravenous drug users (3 of 308; 1%) and hemophiliacs (1 of 165; 0.6%) with or without HIV-1 infection. Thus, both M. penetrans and Kaposi's sarcoma (KS) occur primarily in male homosexuals and rarely in other groups of patients at high risk of AIDS. Among 414 HIV-1-infected patients, statistical analysis revealed those with M. penetrans antibody were 11.7 times more likely to develop KS. Furthermore, among 198 HIV-infected homosexuals (149 with AIDS and 49 without AIDS), those with KS had M. penetrans-specific antibody at a significantly higher frequency (28 of 47; 59.6%) than did those without KS (27 of 102 with AIDS [26.5%] as well as 13 of 49 without AIDS [26.5%]; odds ratio = 4.1, P < .001). M. penetrans is apparently transmitted sexually through homosexual activity and is epidemiologically linked to formation of KS in homosexual men with AIDS. Parallel tests with M. genitalium revealed no similar link to KS in the same study sample.

AIDS-Related Opportunistic Infections↗
PubMed1992

Generation of neutrophil-chemoattractant by degradation of tumor cell membrane protein.

Polymorphonuclear leukocytes (PMN) infiltrating into tumors are assumed to be the result of a migration in response to a tumor-derived chemotactic factor. It is hypothesized that tumor-derived chemotactic factors, which are supposed to be in aggregates, can be exposed by proteolytic degradation of the tumor cell membrane protein (TCM). The TCM suspension made from either Sarcoma 180 or Ehrlich ascites tumor after incubation with Varidase at 37 degrees C for six to eight weeks is referred to as a degraded TCM protein (DTCM). The purpose of this study was to detect whether or not the DTCM was chemotactic for PMNs. Chemotactic activity was assayed by a sponge-matrix model and expressed in the number of PMNs infiltrating into the sponge per mouse after intrasponge injection of the DTCM, dose range, 0.4-0.005 mL. Maximal response to DTCM was restricted to the limited dose between 0.01 and 0.02 mL. Quantities of DTCM > 0.02 mL caused a response in roughly reciprocal proportion to the dose of DTCM. Changes in the circulating leukocyte count in response to an intravenous (i.v.) injection of DTCM was biphasic. The initial relative leukopenia was followed by leukocytosis within 24 hours in rats surviving the effect of DTCM doses < 0.5 mL. However, in rats with i.v. injections of higher doses, profound leukopenia was present at death. The mice, after an intraperitoneal (i.p.) injection of DTCM, dose range, 0.5-1.0 mL, died between 16 and 24 hours after the injection. The bone marrow of these mice showed complete depletion of PMNs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Hyaline-cell rich chondroid syringoma. A tumor mimicking malignancy.

We report three cases of chondroid syringoma composed almost entirely of hyaline cells and occurring in the soft tissues. These lesions were confused with a variety of malignant neoplasms, including malignant melanoma, myxoid chondrosarcoma, and alveolar soft part sarcoma. The tumors occurred in two men and one woman aged 37, 75, and 71 years, respectively, and involved the heel, great toe, and face. All cases arose in the subcutaneous tissue or fascial layer and ranged in size from 0.8 to 2.0 cm. The neoplasms were composed of plasmacytoid hyaline cells with variable amounts of myxoid stroma. Two of the chondroid syringomas contained rare duct structures. One contained cartilage lobules but no ducts. All were well circumscribed. Immunohistochemistry showed positive staining for keratin, S-100, and vimentin in all cases. Muscle markers, including desmin, smooth-muscle actin, and muscle-specific actin, were negative. Follow-up has showed no evidence of recurrence or metastasis.

Adenoma, Pleomorphic↗
PubMed1992

[Fundamental study on hyperthermic chemotherapy using adriamycin-loaded hydroxyapatite].

We developed a porous hydroxyapatite ceramic (HAP) incorporating adriamycin (ADM), that is, ADM-HAP as a new delivery system (DDS) to release ADM gradually. We also researched the possibility of hyperthermic chemotherapy using ADM-HAP by in vitro and in vivo experiments. As for in vitro experiments, we implanted HAPs into uniform Agar-Phantom, and observed thermal distribution generated by Thermotron-RF 8 using thermography. Then we found the hot spot that the edge temperature of HAPs always at the range of 0.5-0.7 degrees C than in the other regions. On the other hand, slow constant release (1%) of ADM from ADM-HAP in PBS was recognized for 24 hrs up to 30 days. When the incubating temperature was shifted up to 42.5 degrees C or 44 degrees C from 37 degrees C, the quantity released over 24 hrs increased about 1.1-fold or 1.3-1.4-fold of the cases at 37 degrees C, respectively. In the in vivo experiment, we inoculated Sarcoma 180 cells in the leg of ddY-mice, and measured the tumor growing times by the treatment of hyperthermia+ADM (whole body), hyperthermia+ADM (tumor region) or hyperthermia+ADM-HAP (tumor region). Then we found that the effect of hyperthermia with ADM-HAP inhibited synergistically the tumor growth as compared with hyperthermia with ADM. Consequently, we succeeded in tumor growth inhibition by increasing the temperature and by limiting ADM release to only a target region using hyperthermia with ADM-HAP.

Animals↗
PubMed1989

[Clinical evaluation of limb-salvage procedures in malignant bone tumors--a study of 54 cases].

Recent advances in therapy such as local and systemic chemotherapy, wide resection, and aggressive thoracotomy improved the survival of the patients with malignant bone tumors. Since 1981, we have performed limb-salvage operations for 54 cases of malignant bone tumors of the extremities. In this study, we report the rate of local recurrence and the prognosis of the patients. We treated 37 osteosarcomas, 8 malignant fibrous histiocytomas of bone, 3 Ewing's sarcomas, 3 parosteal osteosarcomas, 2 chondrosarcomas, and one fibrosarcoma. The age of the patients ranged from 11 to 65 years (mean, 18.5). The male/female ratio was 2:1. The surgical stage was 47 at II B and 7 at III. The follow-up period was 14 to 84 months (mean 36). They received preoperative chemotherapy including intraarterial infusion of Adriamycin, and postoperative chemotherapy for ten months. Local recurrence was detected in 2/54 (3.7%). Lung metastases (Stage II B) developed in 9/47 (19.1%). Five of them (10.7%) died of metastasis, one is alive with metastases, and 41 cases are now disease-free. Six of seven cases (Stage III) died of metastasis, despite aggressive chemotherapy and thoracotomies.

Adolescent↗
PubMed1994

Activation of the proto-oncogene c-myc and c-fos by c-ras: involvement of polyamines.

Rat kidney cells infected with a temperature-sensitive mutant of Kirsten sarcoma virus (Ki-MSV ts 371) expressed Ki-Ras at 37 degrees C but not at 42 degrees C. This expression of the oncogene was accompanied by an increase in the activity of ornithine decarboxylase (ODC) and the accumulation of putrescine. Elevation of cellular polyamine content triggered the transcription of c-myc and c-fos. alpha-Difluoromethylornithine, a specific inhibitor of ODC, prevented the transcription of c-myc in cells grown at 37 degrees C. Putrescine, at physiological concentrations, triggered the transcription of c-myc and c-fos in cells grown at 42 degrees C, when Ki-ras was not expressed. It has been suggested that polyamines participate in a cascade of events leading to the communication between membrane-bound and nuclear oncogene products. These findings may attribute a new function to the naturally occurring polyamines.

Animals↗
PubMed1991

Low-grade stromal sarcoma: a benign appearing malignant uterine tumour; a review of current literature. Differential diagnostic problems illustrated by four cases.

Clinicopathological features of four cases of low-grade stromal sarcoma (LGSS) are presented. Established diagnostic criteria have been followed. Differential diagnoses are discussed with emphasis on the difficulties in separating LGSS from the very common benign uterine leiomyomas. The finding of infiltrating cells, morphologically similar to the cells of the proliferating endometrium, has been decisive for our diagnoses. Prognosis and treatment are discussed on the basis of a compilation of data collected from 31 clinicopathological studies. Of 91 patients with initial disease confined to the uterus, 37 (41%) developed recurrence within 10 years. In contrast to most other uterine sarcomas LGSS is amenable to surgery. We recommend total abdominal hysterectomy with bilateral salpingo-oophorectomy in cases of initial disease confined to the uterus, and radical or palliative surgery in cases of extra-uterine involvement. Long-term follow-up with surgical intervention in cases of recurrence or metastases is advocated.

Aged↗
PubMed1989

Microinjection of a monoclonal antibody against a 37-kD protein (tropomyosin 2) prevents the formation of new acetylcholine receptor clusters.

We have shown previously that chick muscle cells transformed with Rous sarcoma virus are unable to form clusters of acetylcholine receptors (AChRs) (Anthony, D. T., S. M. Schuetze, and L. L. Rubin. 1984. Proc. Natl. Acad. Sci. USA. 81:2265-2269) and are missing a 37-KD tropomyosin-like protein (TM-2) (Anthony, D. T., R. J. Jacobs-Cohen, G. Marazzi, and L. L. Rubin. 1988. J. Cell Biol. 106:1713-1721). In an attempt to clarify the role of TM-2 in the formation and/or maintenance of AChR clusters, we have microinjected a monoclonal antibody specific for TM-2 (D3-16) into normal chick muscle cells in culture. D3-16 injection blocks the formation of new clusters but does not affect the preexisting ones. In addition, TM-2 is concentrated at rat neuromuscular junctions. These data suggest that TM-2 may play an important role in promoting the formation of AChR clusters.

Animals↗
PubMed1985

Recognition of mos-related proteins with an antiserum to a peptide of the v-mos gene product.

A mos-specific antiserum was generated by injection of rabbits with a peptide predicted from the sequence of the v-mos gene of Moloney murine sarcoma virus (MuSV) strain 124. The peptide is composed of amino acids 37-55 (cyclized at the cysteine residues) conjugated to keyhole limpet haemocyanin. This serum [anti-mos(37-55c)] specifically recognized p37mos in MuSV-124 acutely infected NIH-3T3 cells, P85gag-mos in 6m2 cells, an NRK clone infected with the temperature-sensitive mutant (ts110) of Moloney MuSV, and P100gag-mos in 54-5A4 cells, an NRK clone infected with a spontaneous revertant of ts110. An additional protein of Mr 55000 from uninfected cells was recognized by this serum. Reactivity of the serum toward the v-mos-containing proteins and the 55K protein was completely inhibited by prior incubation with free peptide. The 55K protein was not recognized by antisera made from synthetic peptides prepared from the C-terminal eight or 12 amino acids of v-mos.

Animals↗
PubMed1985

Correspondence between immunological and functional domains in the transforming protein of Fujinami sarcoma virus.

Monoclonal antibodies reactive with either gag or fps portions of the wild-type Fujinami sarcoma virus transforming protein have been used to probe the structure of proteins encoded by mutant genomes constructed in vitro. The pattern of immunoreactivity suggests that the functional domain defined in genetic studies (Stone et al., Cell 37:549-558, 1984) corresponds to a discrete immunological domain in the native, wild-type Fujinami sarcoma virus protein. At least one mutation affecting both the structure and function of the proposed NH2-terminal fps-specific domain encodes a product with high specific activities in kinase assays. Furthermore, a cell line expressing high levels of this mutant protein is only moderately transformed. The striking correspondence between the immunological domain defined here and the functional domain inferred from the results of transfection experiments suggests that this non-kinase-specifying region constitutes a discrete structural as well as functional component of the viral protein.

Animals↗