Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two schedules of cis-dichlorodiammineplatinum(II) (cis-platinum) were evaluated for therapeutic efficacy and toxicity in children with malignant diseases resistant to standard therapy. Initially, cis-platinum was given as a rapid iv bolus injection at a dose of 15 mg/m2/day for 5 days every 3 weeks. The second schedule of cis-platinum was a dose of 1 mg/kg/week administered as an 8-hour infusion with mannitol. furosemide, and hydrating fluids. Using the daily schedule, no responses were seen among 23 children with acute lymphatic leukemia and only eight responses were noted among 47 children with solid tumors. Using the weekly schedule, three responses were noted among 25 children with solid tumors. Responses were observed in seven children with neuroblastoma, two with osteosarcoma, one with embryonal testicular carcinoma, and one with an endodermal sinus tumor. With one exception (a 4-year-old child with neuroblastoma), all responses were of short duration. The most common side effects with both schedules were nausea and vomiting which were usually controlled with antiemetics. The dose-limiting toxicity, especially on the 5-day schedule; was renal function impairment. Only one child who received cis-platinum weekly as an 8-hour infusion with diuresis had elevation of the serum creatinine level. Protocols are being initiated to determine the therapeutic effectiveness and toxicity of combination therapy with cis-platinum in children with neuroblastoma and osteosarcoma.
 ...
PMID:Evaluation of cis-dichlorodiammineplatinum(II) in children with advanced malignant diseases: Southwest Oncology Group Studies. 29 82

During the past 3 years, eight hospitals and one cooperative study group have reported their initial clinical results with cis-dichlorodiammineplatinum (II). The most popular clinical schedule was 15-25 mg/m2/day for 5 days repeated every 3-4 weeks. Almost all patients had extremely advanced disease. Of 323 patients in whom response could be evaluated, there were 12 complete responses, 25 partial responses (greater than 50% decrease in tumor size), and 23 improvements (greater than 50% decrease in tumor size) for a 19% overall response rate. The tumor most sensitive to cis-dichlorodiammineplatinum (II) was testicular carcinoma in which seven complete responses, three partial responses, and three improvements were observed in 16 patients treated at Roswell Park Memorial Institute. Other sensitive tumors were lymphoma (63% response and improvements), squamous cell carcinoma of the head and neck (41% response and imporvements), and ovarian carcinoma (40% response and improvements). Complete responses were also seen in one patient with thyroid carcinoma and two with bladder carcinoma, while partial remissions were recorded in two patients with breast carcinoma and one patient each with acute myelogenous leukemia, endometrial carcinoma, renal carcinoma, malignant thymoma, neuroblastoma, adenocarcinoma of the lung, and an undifferentiated tumor of unknown origin. Five major types of toxicity were encountered: gastrointestinal, hematopoietic, immunosuppressive, otologic, and renal, with the last two generally the most serious. Serial audiometry testing can generally warn of the otologic toxicity and thus prevent permanent acoustic damage. Renal toxicity, which is similar to that seen with heavy-metal poisoning, appears to be dose related, cumulative, and only partly reversible, thus, severely limiting the repeated administration of cis-dichlorodiammineplatinum (II). Recent laboratory studies suggest that combination chemotherapy with this drug may be rewarding. Studies of this nature should be pursued along with attempts to find more effective less toxic platinum compounds.
 ...
PMID:Review of the current clinical status of platinum coordination complexes in cancer chemotherapy. 110 40

Four newly-established human tumor cell lines, have been irradiated at dose rates of 150 and 3.2 cGy/min to compare their capacity to repair radiation damage. They included a neuroblastoma, a germ-cell carcinoma of the testis, a large cell carcinoma of the lung, and a carcinoma of the cervix. The four lines varied in their sensitivity to high dose-rate irradiation, with the neuroblastoma being most radiosensitive and the lung and cervix tumors the most radioresistant. The extent of dose sparing associated with lowering the dose rate to 3.2 cGy/min was similar in three of the lines but somewhat greater in the case of the cervix carcinoma cell line. The presence of non-toxic concentrations of the poly(ADP-ribose) transferase inhibitor, 3-aminobenzamide (3-AB), enhanced the response of 3 of the 4 tumors to irradiation; it failed to modify the sensitivity of a lung carcinoma cell line. The extent of sensitization was generally similar at high and low dose rate. Measurement of poly(ADP-ribose) transferase activity in control and irradiated cells showed the neuroblastoma cells to contain much higher initial levels than the other three lines but there were no significant differences in the extent of stimulation in enzyme levels after irradiation. Survival curves obtained at low dose-rate help define the initial slope of the acute curve and it appears that 3-AB may exert a differential effect among human tumors in modifying this component.
 ...
PMID:Differential radiosensitization by the poly(ADP-ribose) transferase inhibitor 3-aminobenzamide in human tumor cells of varying radiosensitivity. 313 29

Bleomycin (Blenoxane) and cisplatin (Platinol) are two anticancer drugs with activity for head and neck tumors. Introduced into clinical use in the past ten years, bleomycin is used primarily in the chemotherapy of squamous cell carcinomas, lymphomas, and testicular carcinoma, while cisplatin is effective against testicular and ovarian carcinoma, head and neck cancer, bladder cancer, and neuroblastoma. Bleomycin is rapidly excreted renally (T 1/2 beta = 2-4 hr) although enzymatic inactivation also occurs in many tissues. Cisplatin is nonenzymatically converted to highly protein-bound metabolites, which then undergo renal elimination, but total body clearance occurs much more slowly than with bleomycin (T 1/2 beta = 40-50 hr). Both agents have acute and chronic toxicities; the acute toxicities are generally reversible but cause a great deal of patient discomfort, while the chronic toxicities are often irreversible and dose-limiting. For bleomycin, the acute toxicities are mucocutaneous and pyretic, while severe nausea and vomiting represent the major acute toxicities of cisplatin therapy. Cumulative dose-related pulmonary toxicity is the most serious chronic toxicity of bleomycin. The clinical, radiographic, and pathologic presentations are nonspecific, although identification of high-risk patients may be possible with serial pulmonary function tests. Cumulative nephrotoxicity occurs with cisplatin use and its incidence and severity can be reduced by maintaining adequate hydration and diuresis during and following administration of the drug.
 ...
PMID:Clinical pharmacology of bleomycin and cisplatin. 617 47

Bleomycin (Blenoxane) and cisplatin (Platinol) are two anticancer drugs, with activity for head and neck tumors, that were introduced into clinical use in the past ten years. Bleomycin is used primarily in the chemotherapy of squamous cell carcinomas, lymphomas, and testicular carcinoma, while cisplatin possesses significant activity against testicular and ovarian carcinoma, head and neck cancer, bladder cancer, and neuroblastoma. Bleomycin is rapidly excreted renally (terminal phase half-life = 2-4 h), although enzymatic inactivation also occurs in many tissues. Cisplatin is nonenzymatically converted to highly protein bound metabolites, which then undergo renal elimination, but total body clearance occurs much more slowly than with bleomycin (terminal phase half-life = 40-50 h). Both agents have acute and chronic toxicities; the acute toxicities are generally reversible but cause a great deal of patient discomfort, while the chronic toxicities are often irreversible and dose-limiting. For bleomycin, the acute toxicities are mucocutaneous are pyretic; severe nausea and vomiting represents the major acute toxicity of cisplatin therapy. Cumulative dose-related pulmonary toxicity is the most serious chronic toxicity of bleomycin. The clinical, radiographic, and pathologic presentations are nonspecific, although identification of high risk patients may be possible with serial pulmonary function tests. Cumulative nephrotoxicity occurs with cisplatin use, and its incidence and severity can be reduced by maintaining adequate hydration and diuresis during and following administration of the drug.
 ...
PMID:Clinical pharmacology of bleomycin and cisplatin. 617 75

The nude mouse human tumor-bearing system is a useful model for studying the efficacy of new drugs against human tumors. A panel of six selected human tumor heterotransplants was used to assess the activity of m-AMSA. No effect was seen against malignant schwannoma, malignant lymphoma, liposarcoma, neuroblastoma, or malignant melanoma. A testicular carcinoma appeared to respond to m-AMSA: however, statistical evaluation demonstrated that this was not significant. No evidence was found to support the use of m-AMSA as a sensitizing agent for radiation.
 ...
PMID:Evaluation of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA, NSC 249992) on human tumors in nude mice. 689 75

Etoposide is a semisynthetic podophyllotoxin derivative with a broad spectrum of antitumor activity and a relatively high therapeutic index. The synergism in animal with cis-platinum, cyclophosphamide, BCNU, and cytosinarabinoside is interesting for combination regimen. Mechanisms of action are inhibition of nucleoside transfer and of DNA and RNA synthesis, single stranded breaks, inhibition of protein synthesis and of microtubular assembly. While in lower concentrations etoposide is acting cell-cycle-dependent with accumulation of cells in the G2-phase it has, in high concentrations, also a cellcycle-phase-unspecific lethal effect. Most suitable is the oral and i.v. application of etoposide in fractionated doses of 80--120 mg/m2 on 3--5 consecutive days and repetition after 21 [14--28] days. Side effects are dose-limiting bone marrow toxicity, nausea, vomiting, fever, hypotension, phlebitis, mucositis, neuropathy, cardiotoxicity, alopecia. Etoposide is one of the most active single agents in small-cell bronchus carcinoma with a remission rate of 37% (10% CR), and is very active in NHL (36%), testicular carcinoma (37%), AMML (35%), choriocarcinoma (35%), and neuroblastoma (29%). The role of etoposide in combination with other active drugs in these tumors is currently investigated in bronchus and testicular carcinoma and NHL, where etoposide will belong to the drugs of the first choice in the future.
 ...
PMID:[Etoposide VP 16--213)--a podophyllotoxinderivative with high antitumor activity (author's transl)]. 703 50