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)

From May, 1970 through December, 1972, Children's Cancer Study Group entered 112 patients on an amended treatment program for rhabdomyosarcoma and undifferentiated sarcoma in children. These patients had Group II disease with residual tumor remaining after surgery, or metastatic disease at onset. Another group consisted of patients who previously had treatment with surgery and radiotherapy and had recurrent disease. Cyclophosphamide was added to a previously used drug regimen which consisted of actinomycin D and vincristine. The drugs were given sequentially in repeated cycles for 18 months. Of 97 evaluable patients, there were 24 with microscopic residual disease, 37 with gross residual disease, 22 with metastatic disease at onset, and 14 patients who were treated with chemotherapy for the first time with recurrent or metastatic disease. All patients have been followed for 3 or more years. Survival in each group was 70.8%, 43.2%, 27.2%, and 28.2%, respectively. Although the number of complete remissions was greater than with two-drug therapy, survival with three-drug therapy was not significantly different than that seen in the earlier study.
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PMID:Treatment of rhabdomyosarcoma in children with surgery, radiotherapy and chemotherapy. 84 Jan 61

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and 20 per cent of these cancers involve the pelvis or genitourinary system. Radical pelvic surgery, such as exenteration, was considered at one time to be the standard treatment for this cancer which carried a very poor prognosis. Over the past 15 years, a combined modality approach to treating rhabdomyosarcoma, using chemotherapy, radiotherapy, and less radical surgery, has evolved and survival rates have improved. This paper presents a case of rhabdomyosarcoma involving the perineum which was treated by combination chemotherapy of Vincristine, Actinomycin-D, and Cytoxan, followed by wide local excision, interstitial and external beam radiotherapy, and postoperative chemotherapy. The literature on pelvic rhabdomyosarcoma is reviewed and the current approach to treating this cancer using multimodal therapy is discussed.
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PMID:Genital rhabdomyosarcoma: current management and review of the literature. 351 19

Seventy-nine patients with rhabdomyosarcoma (RMS) received treatment at the National Cancer Center Hospital between 1962 and 1985. The patients ranged in age from 4 months to 74 years with a median age of 6 years. Forty-six patients were male and 33 were female. The primary tumor site of RMS was the same as in the previous report. The head and neck region was the most frequent site (40.5%), followed by the extremities (34.1%), genitourinary region (15.2%), trunk (5.1%) and retroperitoneum (5.1%). Histologic types were embryonal RMS in 45 patients, alveolar RMS in 23 patients, pleomorphic RMS in 8 patients and unclassified RMS in 3 patients. As of October 1985, 14 of the 79 patients were still alive. Between 1962 and 1971, 38 patients were not treated by any protocol. After 1972, 41 patients received treatment using a 3 stage-related, multiple-modality program. In the first protocol, chemotherapy consisted of Vincristine, Cyclophosphamide, and Actinomycin-D, and 1 of 18 patients have survived more than 5 years. The cumulative 5-year survival rate of the first protocol was 11.1%. In the second treatment program, which involved Adriamycin in addition to the 3 drugs cited above, 4 of 23 patients have survived more than 5 years. The cumulative 5-year survival rate, 33.2%, was very improved.
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PMID:[Treatment of rhabdomyosarcoma at the National Cancer Center Hospital]. 359 4

Adolescent and young adult patients with pelvic sarcomas continue to have a poor prognosis with standard combination chemotherapy and local irradiation. In addition to a significant risk of local failure, these patients are at high risk for systemic relapse. Twenty-three consecutive patients with Ewing's sarcoma, alveolar rhabdomyosarcoma, undifferentiated sarcoma, or malignant peripheral neuroepithelioma originating in the pelvis were treated with short, intensive combined modality therapy. This approach integrates 5 cycles of VADRIAC chemotherapy (Vincristine, Adriamycin, Cyclophosphamide) with high dose irradiation to the primary lesion (55-60 Gy) and sites of gross metastatic disease (45-50 Gy). Following achievement of a complete response, intensification therapy consisting of total body irradiation (TBI) (8.0 Gy), high dose VADRIAC chemotherapy, and autologous bone marow transplantation is given. All therapy is completed within 6-7 months. No maintenance chemotherapy is given; no surgery is intended. Of the twenty-three patients with pelvic sarcomas treated on this combined modality protocol, 22 achieved a complete remission. Local control was achieved and maintained in all twenty-three patients. With a median follow-up of 21 months since initiation of treatment, there have been nine relapses (all systemic). Seven relapses occurred among the thirteen patients who presented with overt metastatic disease and the other two relapses were among the ten patients with localized disease at presentation. All seven metastatic patients who relapsed have died, whereas both of the relapsed localized patients remain alive. Acute and late toxicities have been acceptable using this aggressive combined modality approach. Induction chemotherapy had a significant impact on reduction of the typically large (greater than 10 cm diameter) soft tissue mass associated with these pelvic tumors, thus facilitating achievement of local control by high dose irradiation. Of 18 patients with measureable soft tissue tumor, all experienced a partial response (greater than 50% reduction in size) following the initial two cycles of chemotherapy given prior to local irradiation. In conclusion, this short, intensive chemoradiotherapeutic regimen is highly effective in controlling the primary lesion (100% local control) and inducing a complete response in a high proportion (96%) of these high risk pediatric and young adult patients with pelvic sarcomas. The role of TBI as "systemic" adjuvant therapy to control micrometastatic disease is discussed as still under investigation.
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PMID:Treatment of pelvic sarcomas in adolescents and young adults with intensive combined modality therapy. 367 16

A case of childhood laryngeal rhabdomyosarcoma is described with a 42 month follow-up and with no evidence of recurrent disease. Treatment included partial excision, postoperative radiotherapy, and chemotherapy with vincristine, actinomycin D, and Cytoxan. Normal laryngeal function has been maintained. Earlier modes of therapy would probably have included total laryngectomy. Recent advances in the combined therapy of childhood rhabdomyosarcoma are reviewed. Resulting cure rates approach 100 per cent in favorable cases. The concept of limited surgical therapy is discussed and is applied to this case.
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PMID:Combination therapy for laryngeal rhabdomyosarcoma. 616 51

The outlook for children with rhabdomyosarcoma has change significantly in these last years. With an adeguate combined modality therapy more than 50% of these children may be cured. The results of the IRS-I indicate that the 3 year relapse-free survival rates are 85% for patients in group I 70% for those in group II, 45% for those in group III and 15% for those in group IV. In addition to the clinical group other significant prognostic factors are histologic cell type (alveolar, unfavorable) and primary site (disease in extremities and in retroperitoneal area, unfavorable). The chemiotherapy must be used in all patients for 12-24 months. The effective drugs are VCR, ACT-D, CTX, ADR combined in different schedules. It has been demonstrated that the effective doses of radiotherapy range from 4000 to 5000 rad and that radiotherapy may be omitted in patients in group I. Now a less aggressive surgical procedures may be employed, and patients with primary tumor in the orbit or in the pelvic organs may be cured saving the eye, or the bladder, the vagina and the uterus.
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PMID:[Rhabdomyosarcoma: therapeutic results and prospectives]. 654 8

A case report of a Stage III botryoid rhabdomyosarcoma of the nasopharynx associated with a six-and-a-half-year survival is presented. Treatment consisted of surgery, radiotherapy (6,000 rads TCT) to the nasopharynx and maxillary sinuses bilaterally, and six cycles of polychemotherapy with Vincristine, Adriamycin, Cyclophosphamide and DTIC, without major loss of function or cosmetic deformity. The histology of the lesion is discussed with reference to recent classification and prognosis. The authors suggest that the histological type and prognosis of rhabdomyosarcoma of the nasopharynx in children may be better correlated in future studies.
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PMID:Botryoid rhabdomyosarcoma of the nasopharynx. 686 97

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood with a dismal prognosis, highlighting the need for novel treatment strategies. Here, we identify a novel synthetic lethal interaction between the histone deacetylase inhibitor (HDACI) SAHA and anticancer drugs in RMS cells. Importantly, SAHA significantly increases chemotherapeutic drug-induced apoptosis in both embryonal and alveolar RMS cell lines, including several anticancer agents that are used in the clinic for the treatment of RMS such as Doxorubicin, Etoposide, Vincristine and Cyclophosphamide. Calculation of combination index (CI) reveals that the interaction of SAHA and Doxorubicin or Etoposide is synergistic. Mechanistically, SAHA causes acetylation of histone H3 protein in RMS cells, indicating that SAHA alters the chromatin context. Also, cotreatment with SAHA and Doxorubicin changes the ratio of pro- and antiapoptotic Bcl-2 proteins with downregulation of Mcl-1 and Bcl-xL, dephosphorylation of Bcl-2 and upregulation of BimEL, thus shifting the balance towards apoptosis. Consistently, SAHA and Doxorubicin cooperate to stimulate activation of Bax and Bak, caspase activation and caspase-dependent apoptosis. Overexpression of Bcl-2 significantly rescues SAHA/Doxorubicin-mediated apoptosis, underscoring the requirement of the mitochondrial apoptotic pathway for the synergistic induction of apoptosis by SAHA and Doxorubicin. Caspase-dependent apoptotic cell death is confirmed by the use of the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk), which significantly decreases SAHA/Doxorubicin-triggered apoptosis. In conclusion, these findings demonstrate that the HDACI SAHA represents a promising strategy to prime RMS cells for chemotherapy-induced apoptosis and warrants further investigation in combination regimens.
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PMID:Chemosensitization of rhabdomyosarcoma cells by the histone deacetylase inhibitor SAHA. 2481 95

Paratesticular embryonal rhabdomyosarcoma (RMS) is a rare tumor arising from the mesenchymal tissues of the spermatic cord, epididymis, testis and testicular tunics. We report three cases of adult paratesticular RMS, two embryonic and one pleomorphic rhabdomyosarcoma. All the patients underwent diagnostic orchidectomy. The work up investigations revealed lung metastases. Chemotherapy with Ifosfamide and Doxorubicin was used in two cases, whereas Vincristin-Actinomycin D and Cyclophosphamide was received in one case. An objective partial response was reported in 2 cases, with complete response in one case. Paratesticular RMS is a rare and aggressive tumor. Because of the absence of protocols designed specifically for adult patients, it is necessary to follow therapeutic guidelines in pediatric protocols.
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PMID:Para testicular rhabdomyosarcoma in adults: three case reports and review of literature. 2587 Jul 34

Rhabdomyosarcoma (RMS) is a common soft-tissue sarcoma in childhood with a poor prognosis, highlighting the need for new treatment strategies. Here we identify a synergistic interaction of the second-generation histone deacetylase inhibitor (HDACI) JNJ-26481585 and common chemotherapeutic drugs (i.e. Doxorubicin, Etoposide, Vincristine, Cyclophosphamide and Actinomycin D) to trigger apoptosis in RMS cells. Importantly, JNJ-26481585/Doxorubicin cotreatment also significantly suppresses long-term clonogenic survival of RMS cells and tumor growth in vivo in a preclinical RMS model. Mechanistically, JNJ-26481585/Doxorubicin cotreatment causes upregulation of the BH3-only proteins Bim and Noxa as well as downregulation of the antiapoptotic proteins Mcl-1 and Bcl-xL. These changes in the ratio of pro- and antiapoptotic Bcl-2 proteins contribute to JNJ-26481585/Doxorubicin-mediated apoptosis, since knockdown of Bim or Noxa significantly inhibits cell death. Also, JNJ-26481585 and Doxorubicin cooperate to stimulate activation of Bax and Bak, which is required for JNJ-26481585/Doxorubicin-induced apoptosis, since silencing of Bax or Bak protects against apoptosis. Consistently, overexpression of Bcl-2 significantly reduces JNJ-26481585/Doxorubicin-mediated apoptosis. JNJ-26481585/Doxorubicin cotreatment leads to caspase activation and caspase-dependent apoptosis, since the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) rescues cells from apoptosis. In conclusion, the second-generation HDACI JNJ-26481585 cooperates with chemotherapeutics to engage mitochondrial apoptosis in RMS cells, demonstrating that JNJ-26481585 represents a promising strategy for chemosensitization of RMS.
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PMID:JNJ-26481585 primes rhabdomyosarcoma cells for chemotherapeutics by engaging the mitochondrial pathway of apoptosis. 2647 75


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