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  • 1
    Electronic Resource
    Electronic Resource
    Loss of Cannabinoid-Stimulated Guanosine 5′-O-(3-[35S]Thiotriphosphate) Binding Without Receptor Down-Regulation in Brain Regions of Anandamide-Tolerant Rats (2000)
    Oxford UK : Blackwell Science Ltd.
    Journal of neurochemistry 75 (2000), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The endogenous cannabinoid anandamide has been reported toproduce well-defined behavioral tolerance, but studies on the possiblemechanisms underlying this process are few and often contradictory. Thepresent study was designed to survey the cellular events involved inanandamide tolerance, in terms of the effects on receptor number, couplingwith G proteins, and activation of the cyclic AMP (cAMP) cascade. Chronictreatment of rats with anandamide (20 mg/kg i.p. for 15 days) resulted inbehavioral tolerance without any change in cannabinoid receptor binding in thebrain regions studied (striatum, cortex, hippocampus, and cerebellum),suggesting that receptor down-regulation was not involved in the developmentof anandamide behavioral tolerance. In contrast, prolonged exposure toanandamide significantly reduced agonist-stimulated guanosine5′-O-(3-[35S]thiotriphosphate) binding in the sameareas, with losses of 〉50%, suggesting that receptor desensitization may bepart of the molecular mechanism underlying this tolerance. Finally, concerningthe cAMP cascade—the most well-known intracellular signaling pathwaysactivated by CB1 receptors—in the brain regions from ratstolerant to anandamide, we found no alteration in cAMP levels or in proteinkinase A activity. We propose that anandamide, unlikeΔ9-tetrahydrocannabinol and other cannabinoids, does notalter the receptor system at multiple levels but that desensitization of theCB1 receptor might account for behavioral tolerance to thedrug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2000.0752478.x
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  • 2
    Electronic Resource
    Electronic Resource
    Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: Are all CMFs alike? (1998)
    Springer
    Annals of oncology 9 (1998), S. 489-493 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant chemotherapy ; breast cancer ; CMF ; radiotherapy ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The first reported effective adjuvant combination regimen for patients withoperable breast cancer comprised oral cyclophosphamide (C) days 1–14with intravenous methotrexate (M) and fluorouracil (F) on days 1 and 8,repeated every 28 days (’classical‘ CMF). These drugs have since beenextensively used with or without endocrine therapies and/or other cytotoxics,as well as with radiation therapy to the chest wall yielding conflictingresults. Although doses and schedules have varied widely, the combination ofthese three drugs has been generically referred to as CMF. Evidence existsthat reducing the dose and/or altering the schedule of CMF (’modified‘ CMF)have compromised its efficacy in metastatic breast cancer. Reduction belowstandard dose of a similar regimen also gave inferior results in the adjuvantsetting. In fact, the recently reported improved outcome of adding radiationtherapy to CMF was only demonstrated in comparisons with a ’modified‘ CMF.Furthermore, trials in women with estrogen receptor-positive breast cancer,which did not demonstrate any significant benefit for the addition of adjuvantCMF to tamoxifen compared with tamoxifen alone, also used ’modified‘ CMF.Therefore, adherence to the ’classical‘ dose and schedule is recommended whenCMF is used in adjuvant therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008236502420
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  • 3
    Electronic Resource
    Electronic Resource
    Oesophageal cancer treatment: Studies, strategies and facts (1998)
    Springer
    Annals of oncology 9 (1998), S. 951-962 
    Details
    ISSN: 1569-8041
    Keywords: Barrett's oesophagus ; multimodality treatment ; oesophageal cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Esophageal cancer is among the ten most frequent cancers in the world. Once diagnosis is established prognosis is poor with five-year survival rates below 10%. Over the last few years, the evidence – base for treatment of oesophageal cancer has changed with the publication of several important articles in this field. This article reviews these and other relevant publications with focus on current evidence which holds potential for an improvement in survival in oesophageal cancer patients. Prevention and early detection represent the mainstay in the ongoing struggle to improve prognosis, which is most stringently linked to tumor stage. Other efforts have been dedicated to optimise surgical treatment, radiotherapy and chemotherapy and to discover the most efficient combinations of these treatment modalities. Strong but not unanimous evidence in favour of a multimodality approach with chemoradiotherapy followed by surgery has accumulated in recent years, and confirmatory trials are presently ongoing. A pathological complete response to chemoradiotherapy has been identified to significantly enhance survival. Among the strategies to achieve higher response rates, variations in the administration of the most commonly used drugs rather than higher drug and radiation dosages seem promising. Occult lymphatic spread has been recognised as a major source of recurrence and has been successfully targeted by three field surgical dissection and extended field radiotherapy. In search of the optimal treatment for patients with oesophageal cancer, a variety of different tracks are being pursued. This review outlines and analyses current treatment approaches and investigates how recent advances may impact on patient management.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008273110272
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  • 4
    Electronic Resource
    Electronic Resource
    Assessment of response in primary chemotherapy for breast cancer (1998)
    Springer
    Annals of oncology 9 (1998), S. 1140-1141 
    Details
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008425205941
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  • 5
    Electronic Resource
    Electronic Resource
    Primary chemotherapy in operable breast cancer with favorable prognostic factors: A pilot study evaluating the efficacy of a regimen with a low subjective toxic burden containing vinorelbine, 5-fluorouracil and folinic acid (FLN) (1999)
    Springer
    Annals of oncology 10 (1999), S. 993-996 
    Details
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; breast cancer ; neoadjuvant ; primary chemotherapy ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Biological considerations support the use of primary chemotherapy in operable breast cancer; and despite wide variations of used regimens, clinical studies consistently show a significant tumor response allowing breast conservation in many patients otherwise canditates for mastectomy. We investigated the efficacy and the acceptance of a combination chemotherapy with vinorelbine, 5-fluorouracil and high-dose folinic acid in operable breast cancer with favorable prognostic factors and tested the relationship of hormone receptor status, Ki67, p53, c-erbB2 and bcl-2 with treatment response. Patients and methods: Thirty-nine patients (median age 51 years, range 36–71 years), eight with T1, twenty-eight with T2 and two with T3 lesions, were treated with 5-fluorouracil (350 mg/m2, i.v. on day 1 to 3) preceded by folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine, given on days 1 and 3 at the dose of 20 mg/m2 (FLN regimen). Therapy was administered on an outpatient basis every three weeks. Non responders had surgery after three courses, while complete or partial responders underwent surgery after six courses. All but one were evaluable for response and toxicity. Results: Objective responses were observed in 23 of the 38 evaluable patients (61%; 95% CI: 46%–76%): three complete responses (8%) and 20 partial responses (53%). Fifteen patients (39%) had stable disease, of whom nine (23%) had minor response. None of the patients had disease progression during treatment. Objective responses were significantly associated with no expression of estrogen and/or progesteron receptors and 〉50% decrease in Ki67 after induction chemotherapy. Tolerance was excellent and none of the patients experienced grade 2 alopecia. Conclusions: The ‘moderate’ efficacy of this regimen might be partially due to the selection of patients with high expression of steroid hormone receptors and low proliferation rate, which have an unfavorable impact on response to this chemotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008389106575
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of 2-methyl-4-chlorophenoxyacetic acid on the catalase liver activity of chicken embryos (1988)
    Springer
    Bulletin of environmental contamination and toxicology 40 (1988), S. 263-267 
    Details
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01881049
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  • 7
    Electronic Resource
    Electronic Resource
    Precipitated and spontaneous withdrawal in rats tolerant to anandamide (2000)
    Springer
    Psychopharmacology 149 (2000), S. 121-128 
    Details
    ISSN: 1432-2072
    Keywords: Key words Anandamide ; Behavioral tolerance ; SR141716A ; Precipitated and spontaneous withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: There is evidence that cannabinoids cause tolerance and physical dependence in humans and animals. Objectives: The aim of this work was to study whether the endogenous ligand for the cannabinoid receptor, arachidonylethanolamide (anandamide), induced behavioral tolerance and physical dependence in rats. Methods: Rats were injected with anandamide (20 mg/kg IP) daily for 2 weeks. To assess tolerance, on days 1, 8 and 15 of treatment rats were observed and behavior was tested. Two common methods were employed to assess physical dependence: interruption of anandamide dosing and vehicle substitution or administration of the cannabinoid CB1 receptor antagonist SR141716A (3 mg/kg IP). Results: Full or partial tolerance developed to the classical behavioral effects elicited by the cannabinoids: hypothermia, catalepsy, hypomotility, decrease in stereotypic activity (rearing and grooming) and hindlimb splaying. No tolerance to anandamide was observed for reduced defecation. An abstinence syndrome appeared after abrupt cessation of cannabinoid intake and after withdrawal precipitated by SR141716A; the withdrawal signs were scratching, licking and biting, eating of feces, ptosis, arched back, wet dog shakes, head shakes, myoclonic spasms, writhing, forepaw fluttering, teeth chattering and piloerection. Conclusions: These findings indicate that the endogenous cannabinoid ligand, administered exogenously, induces both tolerance and physical dependence in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900360
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  • 8
    Electronic Resource
    Electronic Resource
    Hepatic toxicity from cyclophosphamide, methotrexate, fluorouracil (cmf regimen) (1999)
    Springer
    Annals of oncology 10 (1999), S. 1394-1395 
    Details
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008356726147
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  • 9
    Electronic Resource
    Electronic Resource
    Incidence of venous thromboembolism in breast cancer patients during chemotherapy with vinorelbine, cisplatin, 5–fluorouracil as continuous infusion (ViFuP regimen): Is prophylaxis required? (2000)
    Springer
    Annals of oncology 11 (2000), S. 117-118 
    Details
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008364801718
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  • 10
    Electronic Resource
    Electronic Resource
    Response to primary chemotherapy in breast cancer patients with tumors not expressing estrogen and progesterone receptors (2000)
    Springer
    Annals of oncology 11 (2000), S. 1057-1059 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; estrogen receptor ; progesterone receptor ; preoperative chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:We recently demonstrated that in premenopausalpatients with estrogen receptors (ER)-absent tumors, early initiation ofsystemic chemotherapy after primary surgery might improve outcome. These dataindicate a different responsiveness to chemotherapy for tumors not expressinghormone receptors. To test this hypothesis we evaluated the responsiveness topreoperative chemotherapy in patients with ER and progesterone receptors(PgR)-absent tumors. Patients and methods:Patients with biopsy-provenT2–T3, N0–2 breast cancertreated at a single institution from January 1995 to August 1999 withpreoperative chemotherapy were retrospectively evaluated. ER and PgR weredetermined immunohistochemically and classified for this purpose as absent(0% of the cells positive) or positive (≥1% of the cells). Results:On 117 evaluable patients 72 had an objective response(61%). A significant difference in response was observed for patientswith ER and PgR absent compared with those with ER and/or PgR-positive tumors(82% vs. 57%,P = 0.03 Fishers's exact test).Pathological complete remission rates were also significantly different in thetwo groups (23% vs. 7%, respectively; P = 0.04). Conclusions:The different degree of response according to hormonereceptors expression supports the hypothesis that tumors not expressing bothER and PgR might represent a different clinical entity in terms ofchemotherapy responsiveness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008334404825
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