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1. |
Endocrine tumors of the gastrointestinal tract: systemic treatment |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 503-519
Kjell Öberg,
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摘要:
Neuroendocrlne gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, In most patients, tumor growth Is rather slow, and even In advanced metastatlc disease, there Is very little Impairment of the general well-being of the Individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptlde hormones which may be factors In some clinical conditions e.g. carclnold, Zolllnger-Ellison and hypoglycemlc syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrlne tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always In parallel. Systemic treatment of neuroendocrlne tumors mainly consists of chemotherapy, Interferon and somatostatln analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocln with 5-fluorouracll or adrlamycln. This combination produces biochemical responses In up to 60% of patients with endocrine pancreatic tumors; the results In carclnold patients are very poor and response rates are ≤0%. Alpha-lnterferon (IFNa) produces biochemical responses In approximately 50% of patients with malignant carclnoid tumors, significant reductions In tumor size In 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatln analogs have only been used clinically within the last 10 years, but produce symptomatic Improvement in 70% of cases, biochemical responses In 40-60%, but rarely produce any significant reduction In tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carclnold patients both perland intra-operatlvely. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasolntest- Inal peptlde-produclng tumors, benefit most from this type of treatment. Recently, a combination of IFN-a and a somatostatln analog has showed an additive effect of these two drugs. The side effects of streptozotocln and 5- fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction Is impaired renal function. The adverse reactions to IFN-a are mainly flu-like symptoms, fatigue, mild Impairment of liver and bone marrow function and autoimmune reactions In 15% cases. Somatostatln analog treatment causes a low frequency of adverse reactions, those which do occur Include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms. At present, the majority of treatment Is to control the disease. Therapies to cure patients with advanced stages of neuroendocrlne tumors have yet to be established.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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2. |
Phase I clinical trial of ormaplatin (tetraplatin, NSC 363812) |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 520-526
Timothy O'Rourke,
Geoffrey Weiss,
Pamela New,
Howard Burris,
Gladys Rodriguez,
John Eckhardt,
Joanne Hardy,
John Kuhn,
Suzanne Fields,
Gary Clark,
Daniel Von Hoff,
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摘要:
Ormaplatin Is a platinum analog that was developed because of an altered toxlclty profile and non-cross resistance to clsplatln In both In vitro and in vivo models. To determine the toxlcltles and maximum tolerated dose of ormaplatin on a dally times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days at nine dose levels ranging from 1.0 to 15.0 mg/m2/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelosuppresslon were moderate and not dose-llmlting. Dosellmltlng neurotoxlclty, consisting of a sensory peripheral neuropathy, was seen In all five patients who received cumulative doses greater than or equal to 165 mg/m2. This neurotoxlclty was symptomatic In all patients and caused significant functional Impairment In four patients with Inability to walk In two patients. A sensitive atomic absorption spectroscopy analysis performed for one patient at the 13.0 mg/m2/day dose level showed a Cpmu of 163 ng/ml and a t1/2of 10.9 mln for free platinum. A phase II dose could not be determined due to the onset of peripheral neuropathy at low cumulative doses and not at absolute dose levels.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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3. |
A dosing scheme for carboplatin in adult cancer patients based upon pre-infusion renal function and platelet count |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 527-532
Reginald Fish,
Michael Shelley,
Huw Griffiths,
Malcolm Mason,
Malcolm Adams,
Keith James,
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摘要:
The most important risk factors for the development of carboplatin-lnduced thrombocytopenia are total dose, glomerular filtration rate (GFR) and pre-infusion platelet count (Po). Pharmacoklnetlc and toxiclty data from 23 patients with ovarian or testicular cancer were combined with published values from four other centers and the relationships between plasma clearance of ultrafilterable platinum and GFR, and between percentage reduction In platelet count and area under the plasma platinum curve were determined. The scatter in the data was estimated and used in a Monte-Carlo computer simulation to derive the following five-level dosing scheme.The scheme Is based on 5% of patients Incurring grade IV thrombocytopenia. Using this scheme, the majority of patients with ovarian or testicular cancer receiving carboplatin will be given an Initial dose of 900 mg.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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4. |
Structure-activity studies on 2-aryl-4H-3, 1 -benzoxazin-4-ones |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 533-538
John Hadfleld,
Vasilios Pavlidis,
Alan McGown,
Caroline Whltworth,
Philip Perry,
Brian Fox,
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摘要:
Eight benzoxazin-4-ones related In structure to NSC 341964 (1) have been tested for cytotoxlclty In two different cell systems. Two of the benzoxazln-4-ones (3 and 10) showed good cytotoxlclty (ID50=9.9 and 8.9 µM) In P388 cells. The nltrobenzoxazln-4-one (10) caused a significant alteration in cell cycle distribution when administered to P388 cells and was an inhibitor of porcine pancreatic elastase. Structure-activity relationships are discussed.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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5. |
Pharmacokinetic studies on Elobromol in children with brain tumors |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 539-547
Christine Paál,
Valéria Erdélyl-Tóth,
Éva Pap,
Csllla Csáki,
Thomas Ferencz,
Dezsõ Schuler,
Joseph Borsl,
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摘要:
Systemic pharmacoklnetlcs of high dose (500 mg/m2), orally administered Elobromol (dibromodulcltol, DBD) were studied In 16 chemotherapeutlc courses administered to five patients. Cerebrosplnal fluid (CSF) DBD levels were also analyzed In two patients. Bromoepoxydulcitol (BED), dlanhydrodulcltol (DAD) are cytotoxlc, whereas bromoanhydrodulcKol (BAD) and anhydroepoxydulcltol (AED) are Inactive metabolites detectable during the blotransformatlon of DBD. The HPLC method, developed by our team, is suitable for the determination of both DBD and its main metabolites (DAD and BAD). Our publication Is the first In the literature to describe the pharmacokinetic properties of these three hexitol derivatives in pediatric patients. With the exception of one patient, concentration time curves were analyzed by the one-compartment model. From 30 mln following administration, DBD was detectable in all plasma samples for at least 12 h; its concentration, however, was usually undetectable by 24 h. Though highly variable In value, DAD concentrations were detectable during all but one of the therapeutic courses. The following peak concentrations were observed: DBD=3.46-30.63 µM, DAD== 1.70-6.17 µM and BAD=0-5.63 µM. The correlation of AUCBAD and AUCDBD values were exponential up to 200 µM h with no additional increase detectable above this limit: the distribution of AUCBAD and AUCDBD was described by a maximum curve. The possibility of enterohepatlc reclrculation could not be excluded for any of the compounds studied. Each of the three hexitol derivatives was detectable in CSF even if the concentration of the Individual metabolite remained undetectable In plasma. DBD CSF concentrations were almost constant in the period from 2.5 to 8 h following administration. Due to rising DAD concentrations, however, the value of the CSF/plasma concentration ratio was >1. The cumulation of the Inactive BAD metabolite In CSF was also significant.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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6. |
Antiproliferative effects of sodium butyrate in adriamycin-sensitive and -resistant human cancer cell lines |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 548-556
Dominique Fagot,
Christine Buquet-Fagot,
François Lallemand,
Jan Mester,
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摘要:
The proliferation of the MCF7 and MCF7-A (adrlamyclnresistant) and KB-3-1 and KB-A (adrlamycln-resistant) cell lines was arrested by sodium butyrate (NaBut) at 1 mM or higher concentrations. In the MCF7 and MCF7-A cell lines, an accumulation In the d phase was observed, whereas the KB-3-1 and KB-A cell lines accumulated In both G1and G2/M phases. The level of the mRNA coded by the 'early G1'/gene c-myc was high In all these cell lines, and was only transiently decreased by NaBut treatment. The 'late' mRNA coding for the proliferating cell nuclear antigen (PCNA) was also strongly expressed In all the cell lines studied; Incubation with NaBut caused a decrease of the PCNA mRNA In the MCF7 and MCF7-A cells but not In the KB-3-1 and KB-A cells. The antl-oncoproteln p105RB was undetectable In the MCF7 and MCF7-A cells, while the KB-3-1 as well as KB-A cells contained a high level of this protein. Neither the content nor the apparent state of phosphorylatlon of the RB protein were affected by incubation (up to 48 h) with NaBut.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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7. |
Topoisomerase ll-dependent novel antitumor compounds merocil and merodantoin induce apoptosis in Daudi cells |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 557-566
Kirpal Gulliya,
Burchard Franck,
Udo Schneider,
Radhakant Sharma,
Lauren Arnold,
James Matthews,
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摘要:
Three photoproducts of merocyanlne 540 have been Isolated, chemically characterized and synthesized. Two of these photoproducts, merocil and merodantoin, show significant antitumor activity in vitro and in vivo while demonstrating minimal toxlclty to normal cells and tissues. Treatment of lymphoma cells with these compounds resulted In a rapid decline In macromolecular synthesis, DNA fragmentation Inhlbltable by actlnomycln D and cyclohexlmlde, and a marked rise In Intracellular calcium. In vitro analysis revealed that activity of these compounds Is dependent on topoisomerase II. These results are discussed In terms of the novel class of topoisomerase ll-dependent compounds for potential use In chemotherapy.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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8. |
Chemopreventive action by an extract from Ocimum sanctum on mouse skin papillomagenesis and its enhancement of skin glutathione S-transferase activity and acid soluble sulfydryl level |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 567-572
Ritu Prashar,
Ashok Kumar,
S Banerjee,
AR Rao,
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摘要:
We report the chemopreventive property of an ethanollc extract of the leaves of Ocimum sanctum (a traditional medicinal plant) on 7,12-dlmethylbenz[a]anthracene Induced skin papillomagenesis In male Swiss albino mice. A significant reduction In the values of tumor Incidence, average number of tumors per tumor bearing mice and the cumulative number of paplllomas was observed In mice treated topically with the leaf extract of O. sanctum at either the perMnltlatlonal, post-lnltlatlonal stages or continuously at perl- and post-lnltlatlonal stages of papillomagenesis as compared to the corresponding control group. Topical application of Ocimum leaf extract for 15 days resulted In significant 2-fold elevation of reduced glutathione content In the skin of mice (p<0.05). Similarly, glutathione S-transferase activity was also observed to be significantly elevated by 25% compared with the control group (p<0.05) following Ocimum extract treatment.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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9. |
Pharmacokinetics of hydroxyurea in nude mice |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 573-578
Carla Van Den Berg,
John McGill,
John Kuhn,
Julianna Walsh,
Pearl De La Cruz,
Karen Davidson,
Geoffrey Wahl,
Daniel Von Hoff,
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摘要:
Extrachromosomal DNA is the predominant form of gene amplification In human tumors. Hydroxyurea (HU) concentrations of 100-150 IAM have been promising In vitro for extrachromosomal DNA elimination. The study objective was to determine the HU dose-concentration relationship in nude mice with HU doses from 0 to 200 mg/kg. For HU t1/2determination, mice were Injected with HU 100 mg/kg. A plasma concentration of 159 p.M was achieved and a t1/2of 11.3 mln determined. Based on these findings, In vivo elimination studies will require frequent administration of HU to maintain plasma concentrations from 100 to 150 µM.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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10. |
Liposome encapsulated vincristine: preclinical toxicologic and pharmacologic comparison with free vincristine and empty liposomes in mice, rats and dogs |
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Anti-Cancer Drugs,
Volume 5,
Issue 5,
1994,
Page 579-590
Peter Kanter,
Gary Klaich,
Gary Bullard,
John King,
Marcel Bally,
Lawrence Mayer,
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摘要:
A preclinical toxicology study of liposome encapsulated vincristine, free vincristine and empty liposomes was carried out In mice and dogs by single and multiple (dally for 5 days) intravenous Injection. Single and multiple dose Intravenous Injection studies In mice showed the encapsulated form of vincristine to be less toxic than free vincristine. Empty liposomes Injected Intravenously Into dogs were without significant toxlclty. In dogs, the toxlcltles seen with llposomal vincristine were qualitatively similar to those of free vincristine with only minor quantitative differences. The principal toxiclties of free and llposomal vincristine in dogs were anorexia, weight loss, pyrexla, myelosuppresslon and gastrointestinal toxlcity. After single high doses of either formulation gastrointestinal toxlcity was the dose-llmlting toxlcity, while either hematologlc or gastrointestinal toxiclty was dose limiting after multiple dose administration of either drug. Histopathologlc lesions of Importance were bone marrow atrophy, necrosis and atrophy of the lymphoprollferatlve tissues, necrosis of gastrointestinal tract mucosa, liver and pancreas, and hemorrhage. Distribution studies in rats showed significantly higher vincristine levels In serum, spleen, liver, trachea, jejunum, cerebrum, lung, Ischiatic nerve and heart, and significantly lower levels In colon, stomach, salivary gland, thymus esophagus and pancreas after Injection of the liposomeassoclated agent. No toxlcltles were seen that should preclude safe clinical trial of llposomal vincristine in man.
ISSN:0959-4973
出版商:OVID
年代:1994
数据来源: OVID
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