Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purpose. Rhabdomyosarcoma (RMS) is an embryonal tumor thought to arise from skeletal muscle cells that fail to differentiate terminally. The majority of RMSs express MyoD, a protein essential to the differentiation of skeletal muscle. It was recently shown that during myogenesis, MyoD activates the expression of the cyclin-dependent kinase inhibitor (CDKi), p21, which itself plays a critical role in normal muscle development. To investigate the integrity of the MyoD/p21 pathway in RMS, we analyzed p21 and its relationship to MyoD expression in RMS.Methods. A panel of RMS samples was assembled from primary biopsies and from cell lines. Integrity of p21 was analyzed by single-strand conformation polymorphism (SSCP) and sequencing. Expression of p21 and MyoD was determined by Northern blot analysis, and the ability of exogenous p21 to arrest the cell cycle of RMS cell line was determined by transfection studies.Results. Our analysis indicates that although p21 is wild type in RMS, there is an inverse correlation between the levels of p21 and MyoD in these tumors. Tumors that express significant amounts of MyoD fail to express p21. This does not appear to be the result of mutations within the potential CACGTG sites present in the p21 promoter region or in the coding region of p21. An additional group of RMSs express very high levels of p21 but express little, if any, MyoD. Furthermore, RD, a RMS cell line which expresses high levels of endogenous p21, undergoes withdrawal from the cell cycle following forced expression of p21, suggesting that the pathway which would lead to G(1) arrest from endogenous p21 activity is defective.Discussion. These data suggest that the interaction between p21 and MyoD is defective in RMS although the precise nature of the defect remains to be elucidated.
Sarcoma 1997
PMID:Disruption of the MyoD/p21 Pathway in Rhabdomyosarcoma. 1852 Dec 15

Purpose. Post-operative radiotherapy (RT) is routinely applied in the treatment of several human tumours. The aim of the present study was to investigate the value of post-operative RT in a rat model.Methods. Experiments were performed using the rhabdomyosarcoma R1H of the WAG/Rij rat. Animals were randomized to different treatment schedules: surgery, RT or a combination of both. Tumours were excised at different sizes (0.1-4.5 g) aiming for complete macroscopic resection. RT (60 Gy in 30 daily fractions over 6 weeks) was applied either primarily or to the former turnout site from the third post-operative day. Tumour growth delay, time to recurrence and local tumour control were used as endpoints.Results. Pre-operative tumour size determined the time and rate of recurrence. The larger the tumour, the shorter the time to relapse and the higher the recurrence rate. The 50% local control rate (LCR(50)) for surgery was found in tumours with a mass of 0.8 g. For post-operative RT a LCR(50) was achieved for tumours with a mass of 1.1 g. For larger turnouts (> 1.1 g), however, the rate and time course of relapse were similar for both the group receiving RT alone and the group receiving post-operative RT.Discussion. In this model the tumour mass at excision governs the prognosis. Relatively small R1H turnouts may recur despite complete macroscopical resection. With regard to the LCR, the outcome for larger tumours is improved with post-operative RT (60 Gy/6 weeks) than compared with surgery alone. The factor is 1.3. Within a certain range of tumour sizes, combined treatment (surgery + RT) can improve the outcome considerably.
Sarcoma 1997
PMID:Post-Operative Radiotherapy of the Rhabdomyosarcoma R1H of the Rat. 1852 Dec 16

Purpose/results/discussion. Recurrent chromosomal translocations are common features of many human malignancies. While such translocations often serve as diagnostic markers, molecular analysis of these breakpoint regions and the characterization of the affected genes is leading to a greater understanding of the causal role such translocations play in malignant transformation. A common theme that is emerging from the study of tumor-associated translocations is the generation of chimeric genes that, when expressed, frequently retain many of the functional properties of the wild-type genes from which they originated. Sarcomas, in particular, harbor chimeric genes that are often derived from transcription factors, suggesting that the resulting chimeric transcription factors contribute to tumorigenesis. The tumor-specific expression of the fusion proteins make them likely candidates for tumor-associated antigens (TAA) and are thus of interest in the development of new therapies. The focus of this review will be on the translocation events associated with Ewing's sarcomas/PNETs (ES), alveolar rhabdomyosarcoma (ARMS), malignant melanoma of soft parts (MMSP) (clear cell sarcoma), desmoplastic small round cell tumor (DSRCT), synovial sarcoma (SS), and liposarcoma (LS), and the potential for targeting the resulting chimeric proteins in novel immunotherapies.
Sarcoma 1998
PMID:Molecular alterations in pediatric sarcomas: potential targets for immunotherapy. 1852 Dec 38

Patient. We report a 51-year-old male presenting with Grade III rhabdomyosarcoma.Discussion. A case of rhabdomyosarcoma which developed in proximity to a metal surgical implant is described. Few cases have been reported in the world in humans.The therapeutic approach to the disease is presented, together with a brief review of literature.
Sarcoma 1999
PMID:A Case of RhabdomyoSarcoma Following a Metal Surgical Implant. 1852 Dec 78

Purpose. To enumerate lessons from studying 4292 patients with rhabdomyosarcoma (RMS) in the Intergroup Rhabdomyosarcoma Study Group (IRSG, 1972-1997).Patients. Untreated patients < 21 years of age at diagnosis received systemic chemotherapy, with or without irradiation (XRT) and/or surgical removal of the tumor.Methods. Pathologic materials and treatment were reviewed to ascertain compliance and to confirm response and relapse status.Results. Survival at 5 years increased from 55 to 71% over the period. Important lessons include the fact that extent of disease at diagnosis affects prognosis. Re-excising an incompletely removed tumor is worthwhile if acceptable form and function can be preserved. The eye, vagina, and bladder can usually be saved. XRT is not necessary for children with localized, completely excised embryonal RMS. Hyperfractionated XRT has thus far not produced superior local control rates compared with conventional, once-daily XRT. Patients with non-metastatic cranial parameningeal sarcoma can usually be cured with localized XRT and systemic chemotherapy, without whole-brain XRT and intrathecal drugs. Adding doxorubicin, cisplatin, etoposide, and ifosfamide has not significantly improved survival of patients with gross residual or metastatic disease beyond that achieved with VAC (vincristine, actinomycin D, cyclophosphamide) and XRT. Most patients with alveolar RMS have a tumor-specific translocation. Mature rhabdomyoblasts after treatment of patients with bladder rhabdomyosarcoma are not necessarily malignant, provided that the tumor has shrunk and malignant cells have disappeared.Discussion. Current IRSG-V protocols, summarized herein, incorporate recommendations for risk-based management. Two new agents, topotecan and irinotecan, are under investigation for patients who have an intermediate or high risk of recurrence.
Sarcoma 2001
PMID:The Intergroup Rhabdomyosarcoma Study Group (IRSG): Major Lessons From the IRS-I Through IRS-IV Studies as Background for the Current IRS-V Treatment Protocols. 1852 3

Purpose. Transduction of rhabdomyosarcoma (RMS) cells with adenoviral vectors for in vivo and in vitro applications has been limited by the low to absent levels of coxackie and adenovirus receptor (CAR). This study investigates the potential use of low doses of a histone deacetylase inhibitor, depsipeptide (FR901228), currently in Phase II human trials, to enhance adenoviral uptake in six rhabdomyosarcoma cell lines.Methods. Differences in adenoviral uptake in the presence and absence of depsipeptide (FR901228) were assessed using an adenoviral construct tagged with green fluorescent protein. Changes in CAR and alpha(v) integrin expression RMS in response to pretreatment with depsipeptide (FR901128) was determined using RT-PCR.Results. Pretreatment of five of six RMS cell lines with 0.5 ng/ml of depsipeptide (FR901228) for 72 h resulted in increased viral uptake as assessed by green fluorescent protein expression. RT-PCR analysis for CAR showed that in four of these five cell lines, CAR expression was increased 2.8-8.1-fold in cells treated with depsipeptide (FR901228) as compared to control. alpha(v) integrin expression was substantially increased in the one cell line, RH5, which showed increased GFP expression in response to depsipeptide (FR901228) pretreatment but a minimal increase in CAR expression.Conclusions. Depsipeptide (FR901228) can be used as a vehicle to enhance adenoviral transduction in a majority of RMS cells. The mechanism of increased viral uptake appears to mediate via upregulation of CAR.
Sarcoma 2004
PMID:Low Dose Histone Deacetylase Inhibitor, Depsipeptide (FR901228), Promotes Adenoviral Transduction in Human Rhabdomyosarcoma Cell Lines. 1852 90

Sarcoma of the kidney is uncommon and represents between 1% and 3% of all malignant renal tumors. Primary rhabdomyosarcoma of the kidney in adult age is unusual, and only sporadic cases have been reported. This is a very aggressive tumor with dismal prognosis. We report a new case of pleomorphic rhabdomyosarcoma of the kidney in an adult patient.
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PMID:Primary pleomorphic rhabdomyosarcoma of the kidney in an adult. 1862 Oct 1

Sarcoma of the mammary glands is extremely rare. Liposarcoma, leiomyosarcoma, rhabdomyosarcoma, as well as hemangiopericytoma, are part of the soft tissue sarcoma group. Little is known about the progress, prognosis and dissemination of this infrequent tumor entity. We present the case of a woman, who received primary diagnosis of a malignant hemangiopericytoma of the left breast. She underwent a mastectomy with an axillary lymph node sampling (stage pT3 pN0 cM0), as adjuvant therapy was not mandatory. Eight months after diagnosis, the patient presented with lumbar back pain, gluteal pain and right accentuated adynamia in both legs because of a disseminated osseous metastasis. Diagnostic investigation presented a cerebral, pulmonary, cutaneous, hepatic and pleural metastatic disease. Two months after initiation of chemotherapy the patient died. Diagnostic criteria and treatment principles in the metastatic situation are presented in addition to the literature to give a review about this rare malignancy.
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PMID:Metastasized hemangiopericytoma of the breast: a rare case. 1916 99

Rhabdomyosarcomas (RMSs) are the most common soft tissue sarcomas of childhood and adolescence. To date, there are no effective treatments that target the genetic abnormalities in RMS, and current treatment options for high-risk groups are not adequate. Over the past two decades, research into the molecular mechanisms of RMS has identified key genes and signaling pathways involved in disease pathogenesis. In these studies, members of the receptor tyrosine kinase (RTK) family of cell surface receptors have been characterized as druggable targets for RMS. Through small molecule inhibitors, ligand-neutralizing agents, and monoclonal receptor-blocking antibodies, RTK activity can be manipulated to block oncogenic properties associated with RMS. Herein, we review the members of the RTK family that are implicated in RMS tumorigenesis and discuss both the problems and promise of targeting RTKs in RMS.
Sarcoma 2011
PMID:Receptor tyrosine kinases as therapeutic targets in rhabdomyosarcoma. 2125 75

Rhabdomyosarcomas (RMS) are a heterogeneous group of tumors that share features of skeletal myogenesis and represent the most common pediatric soft tissue sarcoma. Even though significant advances have been achieved in RMS treatment, prognosis remains very poor for many patients. Several elements of the Insulin-like Growth Factor (IGF) pathway are involved in sarcomas, including RMS. The IGF2 ligand is highly expressed in most, if not all, RMS, and frequent overexpression of the receptor IGF1R is also found. This is confirmed here through mining expression profiling data of a large series of RMS samples. IGF signaling is implicated in the genesis, growth, proliferation, and metastasis of RMS. Blockade of this pathway is therefore a potential therapeutic strategy for the treatment of RMS. In this paper we examine the biological rationale for targeting the IGF pathway in RMS as well as the current associated preclinical and clinical experience.
Sarcoma 2011
PMID:Targeting the insulin-like growth factor pathway in rhabdomyosarcomas: rationale and future perspectives. 2143 17


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