Disease relevance of Adriblastina

• Like DOX-induced venous reactions, ESO complications resolved spontaneously after several hours and did not predispose patients to skin ulceration or subsequent general hypersensitivity reactions [1].
• N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (Dox) has already shown clinical activity in breast cancer patients [2].
• In the M5076 reticulosarcoma DeDXR was equally effective with DXR, whereas the latter was more active on the PRSCT-5 prostate tumor [3].
• Cytotoxicity of the DOX containing starlike HPMA copolymer was determined on an A2780 human ovarian carcinoma cell line and compared with DOX-containing linear HPMA copolymers [4].
• In the present studies, we attempted to inhibit gammaGT activity in human hepatoblastoma (HepG2) cells to examine whether the administration of gammaGT inhibitors, acivicin (AC) and 1,2,3,4-tetrahydroisoquinoline (TIQ) influences cell proliferation and enhances cytostatic action of doxorubicin (DOX) and cisplatin (CP) on HepG2 cells [5].

Psychiatry related information on Adriblastina

• Time-response studies showed that the cytotoxic effects of Pro are increased for 3 days in human tumor cells, whereas VCR, Dox and 5-Fu showed decreased cytotoxic action after 24 h [6].

High impact information on Adriblastina

• These findings indicate that treatment with etoposide, Ara-C, or doxorubicin up-regulates DR5 levels in a p53-independent manner and sensitizes human acute leukemia cells to Apo-2L-induced apoptosis [7].
• This study suggests the combination of CDDP and Dox is highly effective in BC and SC cancers of the skin and by itself can produce long unmaintained remissions, but when combined with a second modality of therapy, it is capable of producing not only long unmaintained CRs but probable cures in the majority of pts [8].
• CONCLUSIONS: FLIP, an inhibitor of apoptosis induced by cytokines of TNF family, contributes at least partly to Dox-induced sensitization to Fas-mediated apoptosis in cardiac myocytes [9].
• Both of N-acetylcysteine (NAC) and the combination of superoxide dismutase and catalase restored the decreased FLIP in Dox-treated cardiac myocytes to the basal level [9].
• We investigated the molecular mechanism by which Dox sensitizes cardiac myocytes to Fas-induced apoptosis [9].

Chemical compound and disease context of Adriblastina

• METHODS: The pharmacokinetics and metabolism of IF and also of doxorubicin (DOX) were determined in patients receiving IF/DOX neoadjuvant chemotherapy for the treatment of advanced breast cancer [10].
• AIM: To investigate the antiproliferative effect of paeonol (Pae) used alone or in combination with chemotherapeutic agents [cisplatin (CDDP), doxorubicin (DOX) and 5-fluorouracil (5-FU)] on human hepatoma cell line HepG(2) and the possible mechanisms [11].

Biological context of Adriblastina

• FZ was able to reverse dox intracellular tolerance of C6 0.5 cells and to restore dox accumulation at the IC50 to the level observed in sensitive cells [12].
• 4. The negative inotropism of 30-100 microM DOX, EPI, or MEN 10755 correlated with cellular levels of both alcohol metabolites (r=0.88, P<0.0001) and carbonyl anthracyclines (r=0.79, P<0.0001) [13].
• DNA damage induced by DOX was not predictive of cytotoxicity [10].
• Coordinately, cell growth inhibition induced by amrubicin and amrubicinol, but not that induced by DXR, was antagonized by ICRF-193 [14].
• Analog AN-207, formed by linking 2-pyrrolino-DOX to [D-Lys6]LH-RH, and analog AN-152, produced by conjugation of DOX to the same carrier, given i.p. as a single injection or repeatedly 2 days apart at their maximum tolerated doses (MTDs) resulted in a 89-93% inhibition of tumor growth [15].

Anatomical context of Adriblastina

• By confocal microscopy, the subcellular distribution of Ann was identical in sensitive and resistant cells, localizing mostly in the perinuclear structures, while that of Dox was exclusively nuclear in sensitive cells and nuclear and in the cell membrane in resistant cells [16].
• FZ was able, at a relatively high concentration (30 microM), to completely restore dox sensitivity in both cell lines [12].
• As compared with Dox, both Ann and L-Ann induced 3 times more DNA double- and single-strand breaks in KB cells [17].
• The DX content was not modified by amiodarone in the other organs studied (heart, lung, spleen and pancreas) [18].
• Unlike DOX, flavopiridol (FL) did not protect HCT116 cells [19].

Associations of Adriblastina with other chemical compounds

• In addition, we designed and synthesized a highly active derivative of DOX, 2-pyrrolino-DOX (AN-201), which is 500-1000 times more potent than DOX in vitro [20].
• The CDDP resistant tumours were not cross-resistant in vivo to L-PAM, BCNU and Dox, which had been active in vitro, nor to tallimustine, which had been cross-resistant in vitro [21].
• Moreover, we have recently found that an HPMA conjugate containing a combination of both Dox and the aromatase inhibitor aminoglutethimide (AGM) shows significantly increased anti-tumour activity in vitro [2].
• In experiments on isolated guinea pig heart, which is considered a highly predictive model of acute anthracycline cardiotoxicity in humans, 4'-deoxy-DXR was found to be significantly less cardiotoxic than DXR [22].
• 4'-deoxydoxorubicin (4'-deoxy-DXR), a new doxorubicin (DXR) analogue with interesting antineoplastic activity, was tested for its cardiotoxicity in guinea pigs and humans [22].

Gene context of Adriblastina

• DOX-containing cytotoxic LHRH analog AN-152 is scheduled for clinical phase I/IIa trials in patients with advanced ovarian and breast cancers in 2005 [20].
• We thus demonstrate that ectopic expression of Daxx substantially increases the rate of apoptosis upon incubation with death receptor agonists such as Fas and TRAIL as well as upon incubation with the cytotoxic drug doxorubicin (DOX) [23].
• We have tried to elucidate TNF signaling in FLC/DOX [24].
• Instead, p53-dependent activation and apoptosis were not only induced by PFTalpha itself but were also enhanced by a combination of PFTalpha with UVB or Dox [25].
• Certain cytokines might be capable of bypassing this process and here we report on the in vitro effects of Tumor Necrosis Factor alpha, (TNF) on a MDR variant (FLC/DOX) of Friend leukemia [24].

Analytical, diagnostic and therapeutic context of Adriblastina

• To test the efficacy of targeted chemotherapy based on LHRH analogs, we recently developed a cytotoxic analog of LHRH, designated AN-152, which consists of [D-Lys6]LHRH covalently linked to one of the most widely used chemotherapeutic agents, doxorubicin (DOX) [20].
• These models were subdivided into four subgroups randomly: Doxorubicin (DOX)-treated group, TAM-treated group, DOX and TAM group and control group [26].
• Moreover, the correlation between DOX sensitivity and P-glycoprotein expression was assessed by flow cytometry [27].
• Preliminary data indicated a lower percentage of EKG abnormalities in comparison not only with DXR but also with other anthracycline analogues [22].
• Doxorubicin (DOX) was introduced into the starlike HPMA copolymer to evaluate its potential as a drug delivery system [4].

References