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At least 163 records · Page 9Linked to original sources

PubMed2005

Wilms' tumor: the experience of the pediatric unit of Kasr El-Aini center of radiation oncology and nuclear medicine (NEMROCK).

AIM OF THE WORK: The aim of the present work is to study the treatment results of Wilms' tumor patients who had attended the pediatric unit of Kasr El-Aini center of radiation oncology and nuclear Medicine (NEMROCK) from January 1994 to January 2001. PATIENTS AND METHODS: Sixty-two new Wilms' tumor patients attended the clinic (NEMROCK) from January 1994 until January 2001. The diagnosis was confirmed pathologically. Stage I included 22 cases, stage II 17 cases, stage III 16 cases, and stage IV included 4 cases, whereas stage V included only 3 cases. Stage I cases received 6 months of vincristine and dactinomycin. Stage II with favorable histology (FH) received 1 year of vincristine and dactinomycin. Stage III and IV received 1 year of vincristine, dactinomycin and doxorubicin. Abdominal radiation therapy, 1080cGY, was given in case of tumor spillage during surgery either to the involved flank or the whole abdomen depending on whether contamination was limited to the flank only or the whole abdomen. In addition, radiation was given to metastatic sites in stage IV. Stages II, III, IV with unfavorable histology (UH) received 1 year of dactinomycin, vincristine, doxorubicin and cyclophosphamide in addition to radiation therapy. Stage V cases were diagnosed by surgical biopsy and were managed according to stage and pathology. RESULTS: Forty patients (64.5%) had favorable histology while twenty-two patients (35.5%) had unfavorable histology. The 4-year overall survival rate was 70.1%. Stage I, II, and stages III+IV+V with favorable histology had a 4-year overall survival of 82.3%, 56% and 41%, respectively. Stages I to IV with unfavorable histology had a 4- year survival of 65.7%. CONCLUSION: Multivariate analysis revealed that stage and residual disease after surgery significantly affected overall survival; while histopathology and stage affected significantly disease-free survival. Moreover, our study revealed that residual disease after surgery affected significantly the incidence of local recurrence and distant metastases.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Tumor necrosis factor and cytotoxic agents. Effect on squamous carcinoma lines.

The cytotoxicity of dactinomycin (actinomycin D), doxorubicin hydrochloride (Adriamycin), cisplatin, fluorouracil, and methotrexate alone and in combination with recombinant human tumor necrosis factor (rHuTNF) on human squamous cell carcinoma lines was studied by an MTT proliferation assay. The rHuTNF alone caused no inhibition after 24 to 72 hours. All lines investigated showed a dose-dependent response to dactinomycin and doxorubicin. Potentiation of dactinomycin and doxorubicin cytotoxicity occurred with four of six cell lines following incubation of rHuTNF and the drug. No synergistic effect on cytotoxicity was seen with rHuTNF and any chemotherapeutic agent on two cell lines. The addition of rHuTNF did not augment the cytotoxic effect seen with cisplatin, methotrexate, or fluorouracil on any cell line. These results show that rHuTNF can enhance the cytotoxic effect of certain chemotherapeutic agents on squamous cell lines in vitro.

Antineoplastic Agents↗

PubMed1995

Adult Wilms' tumor. Report of two cases and review of the literature.

BACKGROUND: Wilms' tumor is rare in adults. The recommended treatments for patients with Stage II adult Wilms' tumor with favorable histology (FH) nephroblastomas are conflicting. METHODS: Two patients with Stage II, favorable histology, adult nephroblastomas are described. Current treatment modalities are discussed and the literature is reviewed. RESULTS: The first patient, a 52-year-old woman, probably had a late local relapse of a Wilms' tumor 21 years after nephrectomy because of a renal tumor originally diagnosed as reticular sarcoma. In this case, a recurring or an extrarenal Wilms' tumor should have been considered. After the tumor was removed, the patient received adjuvant chemotherapy with dactinomycin and vincristine and was disease free 44 months after diagnosis. The Wilms' tumor in the second patient, a 33-year-old woman, was discovered accidentally and classified as Stage II/FH based on preoperative biopsy. She was treated with radical nephrectomy and adjuvant chemotherapy with dactinomycin and vincristine. This patient was disease free 24 months after surgery. CONCLUSIONS: Surgery and two-drug chemotherapy with dactinomycin and vincristine is suggested for patients with Stage II adult Wilms' tumor with FH nephroblastomas.

Adult↗

PubMed1993

Regulation of chicken Hsp70 and Hsp90 family gene expression by transforming growth factor-beta 1.

Transforming growth factor-beta 1 (TGF beta) is a regulator of protein synthesis in cultured chicken embryo cells (CEC). Preceding a gradual increase in overall protein synthesis, members of the Hsp70 family (Hsp70, Hsc70, and Grp78) and the Hsp90 family (90-2 and 90-3) of molecular chaperones are induced rapidly and represent a new class of TGF beta-inducible proteins (I.M. Takenaka and L.E. Hightower, J. Cell. Physiol., 152:568-577, 1992). Herein, 32P-labeled cDNA probes encoding Hsc70 and Hsp90 were used to show that levels of the corresponding mRNAs increased as a fraction of total RNA and in polysomes within five hours of treatment of CEC with TGF beta. This cytokine did not increase rates of hsc70 and hsp90 gene transcription as measured by run-on transcription assays of isolated nuclei. However, the Hsp RNA inductions were inhibited by dactinomycin, indicating a requirement for newly synthesized RNA. Both Hsc70 and Hsp90 mRNAs had relatively short half-lives, measured by Northern blot analyses of dactinomycin chases, which were not altered substantially in TGF beta-treated cells. In contrast, Hsp mRNA half-lives increased in heat shocked CEC exposed to dactinomycin during recovery, revealing a difference in regulation of these genes in stressed cells compared with TGF beta-treated cells. Our results support the conclusion that hsc70 and hsp90 gene expression is regulated posttranscriptionally in TGF beta-treated CEC, and the mechanism likely involves a nuclear event such as increasing the half-lives of nuclear RNA transcripts, processing, or transport into the cytoplasm.

Animals↗

PubMed1991

Germ cell tumors in children: gonadal and extragonadal.

Sixty-three pediatric patients with germ cell tumors are presented with details of symptoms, histological findings, staging, serological markers, treatment, and response to therapy. The primary sites were: ovarian 32, testicular 17, presacral 7, mediastinal 3, intraabdominal 2, vaginal 1, and right inguinal canal 1. These patients were treated with T2 (sequential use of dactinomycin, doxorubicin, vincristine, and cyclophosphamide, with or without radiation), T6 (combination chemotherapy with cyclophosphamide, bleomycin, dactinomycin, doxorubicin, methotrexate, vincristine), or VAB treatment protocols (velban, dactinomycin, bleomycin, cisplatin). The cure rate for stage I ovarian and testicular germ cell tumors was 100%; for stage III, all primary sites, 82% and for stage IV, all primary sites, 75%. Histology was prognostic in ovarian tumors of the immature malignant teratoma type; the neural type immature teratoma, grades II and III, had the worst prognosis. Initial debulking surgery in combination with chemotherapy and radiation plays an important role in germ cell tumors. Stages II, III, and IV germ cell tumors require aggressive treatment with surgery, radiation, and chemotherapy. For stage I patients, with primary ovarian malignant tumor, cure with surgery alone can be achieved in 50% of the cases and in testicular tumors in about 70% of the patients. For those with stage I and elevated serological markers, it is feasible to follow these markers and give no treatment until there is evidence of persistent elevation or a rise in titers after an initial fall. In those without elevated serological markers, one should take into consideration the size of the tumor and the histological type before taking the "wait and see" approach. These stage I tumors are highly curable when they first present but, if allowed to recur, chemotherapy may not offer the patient such a favorable response and cure rate.

Adolescent↗

PubMed1977

Focal chemotherapy of brain tumours using semipermeable membranes.

Semipermeable silastic rubber membranes can be used to diffuse focally a variety of chemicals including antitumour drugs. Of the eight drugs tested, in vitro tests showed the best diffusion with dactinomycin, mithramycin, and oncovin, and the poorest diffusion with bleomycin, fluorouracil, and thiotepa. Biological testing was performed with mithramycin, dactinomycin, and oncovin using tissue cultures of human glioblastoma and subcutaneous implants of mouse ependymoblastoma. All three drugs caused rapid tissue culture cell death with direct injection, and impeded tumour growth when given intraperitoneally. Dactinomycin by silastic diffusion proved more effective than mithramycin against tissue cultures, but neither drug had a significant effect against local tumours treated with implanted drug capsules. Silastic diffusion of oncovin reduced tumour sizes significantly ipsilateral to the implant, compared to contralateral implants and to untreated controls.

Animals↗

PubMed1975

[Possibilities and limits of pre-therapeutic neoplasm sensitivity cytostatics tests under short-term conditions].

The following cytostatic agents were tested for activity in vivo and in vitro inWalker carcinosarcoma 256 of the rat: cyclophosphamide, triaziquon, 5-fluorouracil, methotrexate, adriamycin, dactinomycin, daunorubicin, hydroxyurea, procarbazin and vincritine. With the exception of vincristine, the results of therapy in vivo could be predicted by using a rapid in vitro test system. This involved, for cyclosphosphamide, triaziquon, adriamycin, and daunorubicin, the measurement of 3H-uridine or 3H-thymidine incorporation. The activities of methotrexate and 5-fluorouracil could be determined from 3H-deoxyuridine incorporation and that of dactinomycin from 3H-uridine incorporation. The results of short-term tests (uring adriamycin, daunorubicin, and dactinomycin) in roughly 100 human tumors were compared with data in the literature on therapy with the same cytostatic agents. Good agreement was found between the results of in vitro tests and the literature data on clinical therapy.

Animals↗

PubMed1991

High-risk metastatic gestational trophoblastic disease. A new dose-intensive, multiagent chemotherapeutic regimen.

Dose-intensive, multiagent chemotherapy for the treatment of high-risk gestational trophoblastic disease has evolved as the treatment of choice for these patients. High-dose methotrexate in combination with etoposide, dactinomycin, vincristine and cyclophosphamide (EMA-CO) has now been demonstrated to be superior to the traditional methotrexate, dactinomycin, cyclophosphamide chemotherapy in patients with prognostic scores of greater than or equal to 8. An attempt was made to improve upon the EMA-CO regimen by increasing the dose intensity of etoposide and adding cisplatin to the high-dose methotrexate, etoposide and dactinomycin. That regimen was used on four patients with ultra-high-risk gestational trophoblastic disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1983

Binding of selected drugs to a "treated" inline filter.

The binding of several drugs to an inline i.v. filter that had been treated to inhibit drug-binding was studied. Solutions of mithramycin, vincristine sulfate, digitoxin, insulin, dactinomycin, and nitroglycerin in both 5% dextrose injection and 0.9% sodium chloride injection were allowed to flow through an i.v. administration set containing a 0.22-micron cellulose ester filter that had been treated with a proprietary agent. Actual administration conditions were simulated by using drug concentrations and flow rates commonly employed in clinical practice. The amount of each drug retained by the filter was determined by assaying aliquots of the solutions sampled before and after the solution passed through the filter membrane. In a second experiment, drug binding to the filter membrane was measured by incubating small pieces of the treated membrane in drug solutions and determining concentrations periodically until equilibrium was reached. Untreated filter membrane pieces were used as a control. In the experiment simulating actual i.v. administration, cumulative binding of mithramycin, vincristine sulfate, dactinomycin, and nitroglycerin to the treated filter was less than 6% of the initial dose infused; approximately 8-12% of the initial amounts of digitoxin and insulin were bound to the filter. In the equilibrium binding studies, the untreated filters bound twice as much digitoxin, 5-7 times as much mithramycin, vincristine sulfate, and dactinomycin, and 20 times as much insulin as the treated filters. The amount of nitroglycerin bound to the treated and untreated filters was not substantially different. Insulin had a greater binding tendency in 5% dextrose injection than in 0.9% sodium chloride injection in both experiments regardless of the filter treatment. Treatment of a cellulose ester i.v. filter with the proprietary agent used in this study facilitates drug delivery through this filter.

Adsorption↗

PubMed1977

Effect of inline filtration on the potency of drugs administered intravenously.

The binding of cephalothin sodium, phenobarbital sodium, dexamethasone sodium phosphate, isoproterenol hydrochloride, digoxin, dactinomycin and phenytoin sodium to three intravenous inline filters--a 5-micrometer stainless steel depth filter, a 0.2-micrometer cellulose ester membrane and a 0.2-micrometer polycarbonate membrane--was studied. The experiments were conducted simulating inline i.v. filtration of these drugs in three i.v. solutions--lactated Ringer's, 5% dextrose and normal saline. Cephalothin was assayed colorimetrically, phenobarbital and phenytoin spectrophotometrically, and the other drugs by radiotracer technique. Binding of the drugs to the filter was found to be insignificant from a therapeutic standpoint, except for dactinomycin which bound to the 0.2-uicrometer filters. The binding of dactinomycin was approximately 13% of the amount administered through cellulose ester and polycarbonate membranes, respectively. The binding occurred during the initial period of filtration of the drug solution. It was concluded that inline filtration of drugs administered in relatively high does should not present any problem concerning the reduction of the therapeutic potency because of filtration.

Cephalothin↗

PubMed1994

Management and outcome of inoperable Wilms tumor. A report of National Wilms Tumor Study-3.

METHODS: The authors reviewed 131 children enrolled in National Wilms Tumor Study-3 (NWTS-3) who received preoperative treatment for tumors unable to be resected at surgery or judged inoperable by imaging evaluation. Preoperative biopsies were performed on 103 patients. Patients were assigned a pretreatment stage: stage II (11 patients), stage III (39 patients), stage IV (66 patients), and unknown (15 patients). The chemotherapy regimen included dactinomycin and vincristine (81 patients), dactinomycin, vincristine, and doxorubicin (30 patients), dactinomycin, vincristine, doxorubicin, and cyclophosphamide (10 patients), and other (8 patients). Preoperative radiation therapy was started concurrently with chemotherapy (27 patients) or because of lack of response (14 patients). Two patients were given preoperative irradiation without chemotherapy. RESULTS: Response to therapy was assessed after the first trial of chemotherapy. Partial responses were noted in 110 patients (85%), 3 had complete responses, 13 had no response or progression of disease, and 5 patients were not able to be evaluated. There were no significant differences in preoperative response to the different chemotherapy regimens. Median time interval from diagnosis to nephrectomy was 58.5 days. When compared with NWTS-3 patients not receiving preoperative treatment, survival was reduced for patients treated preoperatively (88% vs. 74%, respectively, 4-year survival), which was only partially explained by differences in stage distribution. Median duration of follow-up was 5.9 years. Lack of response to the preoperative treatment was associated with a poor prognosis. Eight children died before removal of the primary tumor. All eight had either progressive disease or no response to the preoperative treatment. CONCLUSIONS: The use of preoperative treatment can facilitate subsequent surgical resection in selected patients with inoperable Wilms tumors. Although these very large tumors--judged unable to be resected--have a somewhat worse prognosis, nephrectomy was completed in 93% of patients after preoperative treatment. However, preoperative treatment will lead to less accurate surgical and pathologic staging, and undertreatment should be avoided in these high-risk patients.

Child, Preschool↗

PubMed1980

Bioassay of antibiotics in body fluids from patients receiving cancer chemotherapeutic agents.

Patients receiving antitumor chemotherapy are at increased risk of developing nosocomial infections, and the antibacterial therapy of such infections is often monitored by bioassay. The effect of antitumor agents on seven bioassay procedures using strains of Sarcina, Klebsiella, Clostridium, Pseudomonas, Staphylococcus aureus, and S. epidermidis or Bacillus was evaluated. The minimum inhibitory concentrations of six antitumor drugs, cytarabine, dactinomycin, doxorubicin, 5-fluorouracil, methotrexate, and vinblastine, determined for each of the test organisms, showed that 5-fluorouracil, dactinomycin, and doxorubicin are used at blood levels sufficient to interfere with bioassay procedures. The other drugs have minimum inhibitory concentrations as much as 100 times the expected blood levels. Antibiotic (gentamicin, kanamycin, cephalothin, and carbenicillin) recovery experiments in the presence of therapeutic levels of antitumor agents showed no in vitro inactivation of antibiotic. However, at low cephalothin concentrations (less than 20 microgram/ml) in the presnce of 5-fluorouracil, bioassay results were in error by as much as 100%. The data indicate that bioassay procedures for the determining of antibacterial drug levels may need to be modified for those patients receiving antitumor therapy with 5-fluorouracil, doxorubicin, or dactinomycin.

Anti-Bacterial Agents↗

PubMed1988

Update in cancer chemotherapy: genitourinary tract cancer, Part 7: Gestational trophoblastic neoplasms.

Part 7 of an update of the state of the art of cancer chemotherapy of the genitourinary tract is directed to the treatment of gestational trophoblastic neoplasms. Chemotherapy is the cornerstone of treatment for gestational trophoblastic neoplasms, as these tumors are generally highly curable with chemotherapy.In early stage disease, 40 percent of cases are cured with hysterectomy. In low-risk cases, single-agent methotrexate or dactinomycin provides cure rates of over 90 percent. In high-risk disease sequential methotrexate/dactinomycin, methotrexate plus dactinomycin plus cyclophosphamide or chlorambucil, or methotrexate plus 6-mercaptopurine, or a combination protocol consisting of cyclophosphamide, hydroxyurea, dactinomycin, methotrexate, vincristine (VCR), folinic acid, and doxorubicin (CHAMOCA) produce complete remission rates in 70 to 80 percent of patients. Newer studies are under way with etoposide (VP16), cisplatin, and investigational agents to determine whether better chemotherapy regimens can be developed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

[Action of unithiol on the toxic effect of antitumor preparations].

The effect of unitiol treatment on the toxicity of dactinomycin, 5-fluorouracil, bleomycetin and vincristine was studied in CBA mice. Unitiol treatment was shown to decrease the acute toxicity of dactinomycin and involves a lower loss of body weight. Also, it reduced dactinomycin hemotoxicity which was assessed on the basis of leukocyte count in peripheral blood. Conversely, unitiol potentiated the acute toxic effect of 5-fluorouracil, bleomycetin and vincristine which was matched by body weight loss following treatment with cytostatic drugs. The results point to a wide range of the biological effects of unitiol.

Animals↗

PubMed1992

Tumor necrosis factor and chemotherapeutic agents. Potentiation of cytotoxicity with interferon gamma.

This study examined combinations of the recombinant human cytokines, tumor necrosis factor alpha and interferon gamma, with doxorubicin and dactinomycin as well as other drugs on six squamous cell carcinoma cell lines of head and neck origin using the 3(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide proliferation assay. Interferon gamma significantly enhanced the cytotoxicity of tumor necrosis factor alpha with dactinomycin on all six cell lines investigated, while in four of six cell lines the cytotoxicity of tumor necrosis factor alpha with doxorubicin was significantly augmented by interferon gamma. Additional experiments showed no effect with either cytokine in combination with cisplatin, fluorouracil, methotrexate, or etoposide. These data demonstrate that human recombinant cytokines in concert with certain drugs improve in vitro cytotoxicity and may have a potential for improving in vivo therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1975

Single and combination chemotherapy for primary murine bladder cancer.

Single and combination chemotherapy was evaluated for antitumor activity against N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT)-induced bladder carcinoma in syngeneic mice. Two hundred fifty C3H/He mice having ingested FANFT for 10 months were randomly divided into groups of 30, and the following regimens initiated: cyclophosphamide (Cy), cis-diam-minedichloroplatinum (cis-Pt-II), dactinomycin, adriamycin, Cy plus cis-Pt-II, Cy plus 5-fluorouracil, and Cy plus adriamycin. The drugs were administered for 3 weeks. Each regimen was capable of producing a significant reduction in the mean bladder weight (MBW) when compared to a groups not receiving therapy (108.3 mg). Adriamycin (MBW equal 69.5), dactinomycin (49.6), and cyclophosphamide (42.9) were the best single agents, but the greatest inhibition of tumor growth was achieved by the combination of cyclophosphamide with 5-fluorouracil (38.3) or adriamycin (37.3). These combination chemotherapeutic regimens were able to effect a significant reduction in the number of bladders with Stage C tumors. It is hoped that information gained from this new animal model which allows evaluation of many antitumor drugs within a relatively short period of time will lead to therapeutic trials in patients with locally advanced or metastatic bladder cancer.

Animals↗

PubMed1983

VAB-6 combination chemotherapy in resected stage II-B testis cancer.

Twenty-four patients with resected Stage II-B nonseminomatous germ cell tumors of the testis received adjuvant chemotherapy with the modified VAB-6 regimen for one year. Eighteen patients had nodal category N2B and six nodal category N3 (extranodal extension of tumor). Adjuvant VAB-6 started with two four day inductions at approximately four week intervals. Induction was cyclophosphamide 600 mg/m2 IV, vinblastine 4 mg/m2 IV, dactinomycin 1 mg/m2 IV, bleomycin 30 mg IV on day 1, then bleomycin 20 mg/m2/day by continuous 24 hour infusion for three days, and cis-platinum 120 mg/m2 IV on day 4. Maintenance was vinblastine 6 mg/m2 IV and dactinomycin 1 mg/m2 IV every three weeks. Six patients received a third induction but without bleomycin. All 24 patients remain free of disease with a median follow up of 24 months. Myelosuppression was the major toxicity. Four patients received antibiotics for fever during myelosuppression. In one patient, serum creatinine temporarily rose over 2 mg/dl after cis-platinum. VAB-6 is effective in the prevention of recurrences in resected Stage II-B nonseminomatous germ cell tumors. However, the optimal regimen remains to be defined.

Adolescent↗

PubMed1987

Rhabdomyosarcoma of the uterine cervix. Sarcoma botryoides.

Twenty-one cases of sarcoma botryoides of the uterine cervix, including four previously unreported cases, are reviewed. The age of the patients ranged from 5 months to 48 years, with a peak incidence in the group aged 14 to 18 years. Eighty percent of the patients are alive, with a mean follow-up period of 68 months. Seventy-five percent of the patients had Group I disease, of whom 88% are alive. Eleven of 14 patients (79%) receiving vincristine and dactinomycin based chemotherapy are alive. There were five patients with recurrent disease (24%) of whom two (40%) are alive. The prognosis for cervical sarcoma botryoides is similar to that of other female genital tract embryonal rhabdomyosarcomas. Primary therapy should consist of vincristine and dactinomycin based chemotherapy. Surgery should be guided by the response to initial chemotherapy and should attempt to conserve the function of the bladder, rectum, vagina, and ovaries.

Adolescent↗