摘要:

This article reviews the current general approach to the biochemical diagnosis and the treatment of pituitary tumors with special reference to medical treatment with dopamine agonists and somatostatin analogs. Dopamine agonists are the treatment of choice in patients with prolactin producing tumors. Octreotide is a major advance in the adjunctive treatment of growth hormone producing tumors. Trans-sphenoidal surgical decompression remains the primary treatment modality in gonadotrofinomas, clinically non-functioning pituitary tumors and thyroid stimulating hormone (TSH) producing tumors. Adrenocorticotrophin (ACTH) producing tumors are treated primarily by selective adenomectomy. The biochemical diagnosis of Cushing's syndrome is complex. Bilateral inferior petrosal sinus sampling for ACTH measurement is highly reliable in the differential diagnosis of ACTH dependent Cushing's syndrome, but needs expertise.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Interferon (IFN) related neurotoxicity includes somnolence and confusion, fatigue, lethargy, psychiatric symptoms, conceptual disorganization, neurological deficits, cortical blindness, coma and, rarely, death. The neurologic syndromes seem to be more common In elderly patients, following intramuscular or intravenous administration, at higher doses or frequent injections of IFN-α and in primary renal cell carcinoma. The duration of the treatment was not strongly related to neurotoxicity. Computed tomography findings were non-specific and included atrophy or periventricular lucencies. Electroencephalograph studies demonstrated a generalized increase in slow wave activity which returned to normal after cessation of treatment. Behavioral and mental changes in patients treated with IFN are warning signs, and indicate the need to withdraw treatment.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

This prospective, non-randomized study was designed to evaluate the quality of life (QOL) of cancer patients receiving new cytoxic therapy. QOL was measured using a linear analog self assessment scale (LASA). Cancer patients who received a phase I agent (n= 45) had no significant changes in any of the Individual QOL variables, overall QOL (p= 0.77) or performance status (p= 0.08) following one course of phase I therapy. However, patients who were not eligible for entry on a phase I protocol and who received supportive care (n= 10) experienced significant decreases in overall QOL (p= 0.02) and performance status (p= 0.003) after 1 month of follow-up. This pilot study suggests that participation in phase I trials does not adversely affect one's QOL.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Combinations of drugs are used clinically for the therapeutic advantages they may provide over single agents. We have studied the cytotoxic interaction between four ether phospholipids ET-18-OCH3, BM 41.440, BN 52205 and BN 52211, and several chemotherapeutic drugs (ADM, CDDP, VLB, VP-16, MMC, BLM and MTX) on two human tumor cell lines, A427 (lung) and HT29 (colon). We have used the MTT colorimetric assay to evaluate growth Inhibition and performed isobologram analysis on the IC50data. For both cell lines a synergistic effect has been found between each of the four ether phospholipids in association with CDDP and ADM. In both cell lines only BM 41.440 and BN 52211 act synergistically with VLB while, in A427 cells, only BN 52205 behaves similarly with MMC. These results show that a positive interaction exists between ether phospholipids, spindle poisons and DNA-Interactive drugs.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Methotrexate (MXT) distribution in serum, testicle and epididymis after administration into the tunica vaginalis cavity or intravenously was studied in 36 dogs. The dogs were divided Into two equal groups: (I) an intratunical group In which 20 mg MXT solution was injected into the tunica vaginalis sac of each dog and (2) a parenteral group in which the same MXT dose was administered intravenously. The MXT concentration in serum, testicle and epididymis was determined 2, 4 and 24 h after MXT administration. Clinical and histologic examination of the tunica vaginalis was performed weekly for four consecutive weeks. The intratunical route, in contrast to the parenteral route, achieves a high MXT level in the testicle and epididymis with a low serum level, resulting in low toxicity and high drug efficacy. This route may therefore be suitable for a more effective treatment of testicular and epididymal lesions, notably malignant tumors.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Epirubicin is usually administered in combination with other cytotoxics. Few pharmacological studies address whether relevant clinical Interactions occurin vitrobetween these drugs. This study Investigated whether epirubicin interacted with other cytotoxics or anti-emetics. The following drugs were prepared at pharmacological concentrations, etoposide (200 μg/ml), 5-fluorouracil (120 μg/ml), cisplatin (100 μg/ml), vincristine (100 μg/ml) and cyclophosphamide (1 μ/ml) respectively were admixed with epirubicin (1 μg/ml). Epirubicin was analysed by high performance liquid chromatography using in-line UV and fluorescence detectors. Experiments were performed in quadruplicate. No significant interactions were noted. The experiments were repeated for stemetil and maxoion. Maxoion did not interact with epirubicin but stemetil produced an interfering peak in the assay. We conclude that interaction studies are an Important step In the workup of chemotherapy regimens.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The present work reports the modulation of immuno-competent cell functions by two aza alkyl phospholipids (AAP), BN 52205 and BN 52211. Each compound was compared with 1-O-octadecyl-2-O-rac-glycero-3-phosphocholine (ET-18-OCH3) and/or three drugs used for cancer treatment, i.e. cisplatyl (CIS), 5-fluorouracil (5-FU) and cytosine arabinoside (ARA-C). Interleukin (IL)-1 release from P388D1 cells was increased 2-fold in the presence of 5/μg/ml BN 52205 or BN 52211. However, these stimulations were lower than those obtained with ARA-C, 5-FU and CIS. Compared with ET-18-OCH3, CIS and 5-FU, BN 52205 and BN 52211 were more efficient in increasing tumor necrosis factor production induced by lipopolysaccharide (LPS) from human monocytes.In vitro, all compounds exhibited similar activity in enhancing IL-6 production from human monocytes stimulated with LPS, with the exception of 5-FU and CIS that were inactive. At 20 mg/kg (i.v.), a peak of IL-6 production was reached 2 h after injection of ET-18-OCH, [>1280 U/ml (n= 4,p< 0.001) versus 3.5±0.2U/ml (n= 7)], whereas BN 52211 induced a maximum of IL-6 production after 4 h (77±27 U/ml,n= 5,p< 0.001). BN 52205 induced peaks of IL-6 production after 3 and 6 h (90 ± 62 and 68 ± 35 U/ml, respectively,p< 0.001,n= 4). The proliferation of rat splenocytes was abolished in the presence of BN 52205 and BN 52211 at 10 μg/ml, corresponding to only a partial reduction of IL-2 production at the same concentration. The production of interferon-γ was stimulated 6− to 10-fold in the presence of 1–5 μg/ml BN 52205, BN 52211 and ARA-C. BN 52211 and BN 52205 were also potent enhancers of IL-3 production, whereas 5-FU and ARA-C were inhibitory. These results indicate that in addition to a direct antitumoral effect, AAP may also exhibit immunomodulatory activity bothin vitroandin vivo.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Eight cytostatic clavines were investigated for mutagenicity inSalmonella typhlmurium(reversion of thehisstrains TA98, TA100, TA102 and TA1537), directly and in the presence of a mammalian xenobiotlc metabolizing system, S9 (NADPH-fortified postmitochondrial fraction of liver homogenate from Aroclor 1254-treated rats). Four compounds (festuclavine, 17-bromofestuclavine, 1-allyl-elymoclavine and 1-methyllysergol methyl ether) were direct mutagens, whose activity was enhanced in the presence of S9. The other compounds (1-cyclopentyl-festuclavine, 13-bromo-1-cyclopropylmethylfestuclavine, 6-cyano-1-propyl-6-norfestuclavine and 6-allyl-1-propyl-6-norfestuclavine) showed mutagenic effects only in the presence of S9, as previously observed with other clavines (agroclavine and its 1-propyl and 1-pentyl derivatives). Thus, all investigated clavines may be metabolized to mutagenic products by mammalian enzymes. Bacteriotoxic activities did not correlate with mutagenic activities. The bacteriotoxicity of several clavines was reduced in the presence of S9. The results are discussed with regard to the potential therapeutic use of clavine alkaloids as antimicrobial and antineoplastic agents.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effect of the combination of adriamycin (ADM) with the anti-inflammatory drug rhein (RH) on the membrane redox activity In human glioma cells was investigated. RH, although less effective than ADM, Inhibits ferricyanide reduction by human glioma cells in a dose-dependent manner as well as ferricyanide-induced proton release. The inhibition of the plasma membrane redox system might represent a further mechanism by which RH, other than ATP depletion, affects cell survival. The analysis of the interaction between ADM and RH, performed with the isobolar method, demonstrates a strong synergic response, probably due to an effect on different sites of action. The synergism of the ADM-RH association allows us to achieve a pre-established extent of inhibition with ADM concentrations much lower than with ADM alone. RH might, therefore, represent a very useful tool to improve the therapeutic index of ADM and to lower its general toxicity.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The oncosuppressive effect of melatonin on 9,10-dlmethyl-1,2-benzanthracene (DMBA) induced rat mammary tumorigenesis led us to assess its possible modulatory influence on representative hepatic and mammary drug metabolizing enzymes in DMBA treated female Holtzman rats, reared in short and long photoperiods. Melatonin treated rats in either photoperiod showed a significant induction in hepatic and mammary levels of glutathione (GSH) and cytosolic activities of glutathione S-transferase (GST) when compared with the corresponding controls, along with a significant drop In hepatic microsomal contents of cytochromesb5and P450. This induction of GSH and GST, and depletion of cytochromesb5and P450 by melatonin may possibly be related to its anticarcinogenic potential in this tumor model.

ISSN:0959-4973    

出版商:OVID    

年代:1992

数据来源: OVID