Disease relevance of cyclophosphamide

• Toxicity was severe and dose-related, with the maximum tolerated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m2 [1].
• Systemic manifestations of this vasculitis improved under corticosteriods and cyclophosphamid therapy, a treatment that did not influence either the very high level of anti-myeloperoxidase antibodies or the ventilatory impairment [2].
• Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline [3].
• In contrast, B1R mRNA was not detected in control rat urinary bladder; however, following acute (24 h) and chronic (8 day) CYP-induced cystitis in the rat, B1R mRNA was detected throughout the bladder [4].
• RESULTS: Before administration of DSG, patients had experienced an average of 6.6 relapses (range: 3-12) under an average of 5.4 (range: 2-11) different therapeutic approaches, which included CYC in all cases [5].
• The DNA repair enzyme XRCC1 is a potential treatment predictor for the outcome and survival of anthracycline and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive breast cancer [6].
• MMF, in combination with prednisolone, can induce remission in patients with relapses of AAV intolerant to cyclophosphamide [7].
• Granulocyte macrophage colony-stimulating factor-secreting pancreatic cancer cell lines CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity in patients with advanced pancreatic cancer [8].
• Our data strongly support the use of a combination of cyclophosphamide and AdIL-12 as a novel therapeutic strategy against colorectal carcinoma [9].

High impact information on cyclophosphamide

• Unless CP was administered before the adoptive transfer of TIL, therapy with IL-2 and TIL in these B mice was ineffective in the absence of demonstrable T lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)[10]
• Split femurs from rats given cyclophosphamide (CY) and killed at regular intervals condition media that affect DNA synthesis in a fashion similar to that of HSA-HIA in the rats' sera [11].
• These results suggest that acrolein has a diminished role in mediating the cytogenetic and cytotoxic effects of CP [12].
• The combination of CY and ABMFPP also showed a synergistic anti-P388 leukemia effect which appeared to be related to the initial reduction of the tumor burden by CY and the marked augmentation of the cytotoxicity of both natural killer cells and macrophages by ABMFPP [13].
• These results strongly suggest that the antitumor effect of ABMFPP alone or in combination with CY is at least in part mediated through its augmentation of natural killer cell and/or macrophage activities [13].

Chemical compound and disease context of cyclophosphamide

• Chemical cystitis was induced by cyclophosphamide (CYP) which is metabolized to acrolein, an irritant eliminated in the urine [14].
• So in this study, we examined the effects of the anticancer drugs ADM, CDDP, CPM, MTX and VCR on osteosarcoma cells in vitro [15].
• Adult male rats were treated daily for 18 days with endoxan in doses of 4 mg/kg of body weight or testosterone in doses 2.5 mg per rat [16].
• In this study we monitored pulmonary and cardiac function in 39 patients affected by advanced Hodgkin's disease (stage II B-III and IV) with mediastinal involvement and submitted to an intensive chemotherapy regimen (epirubicin, vincristine, ciclophosphamide, and etoposide) followed by involved field irradiation [17].
• Experiments were run to determine the effect of oral gavage treatment with the cyclopentane influenza virus neuraminidase inhibitor peramivir (BCX-1812, RWJ-270201) in influenza A (H1N1) virus-infected mice that had their immune system suppressed by cyclophosphamide (CP) therapy or in severe combined immune deficient (SCID) mice [18].

Biological context of cyclophosphamide

• When MISO was given as a series of small doses by repeat injection over an 8 h period, in order to stimulate human pharmacokinetics, it significantly enhanced the action of Cy in the SA F tumour [19].
• These results indicate that COX-1 may be involved in modulating the threshold for activating the micturition reflex in the normal rats and also demonstrates that inhibition of COX-2 prevents or reverses the urodynamic changes associated with bladder inflammation induced either by surgery, LPS or CYP treatments [20].
• D5 exposure did not modulate humoral immunity, while the internal control, CYP, produced the expected suppression of the AFC response [21].
• CDDP at 10 microM, CPM at 7.5 microM, ADM at 20 microM and VCR at 150 microM caused 80% cell death of HOS cells after 12 h [15].
• In contrast to their anticlastogenic efficacy neither of the vitamins displayed any significant anti-SCE effect, nor were they active in affecting the inhibition of cell proliferation caused by TR or CP [22].

Anatomical context of cyclophosphamide

• Overexpression of either class 1 or class 3 aldehyde dehydrogenase (ALDH) has been found in cell lines selected for resistance to the oxazaphosphorine (OAP) alkylating anticancer agent cyclophosphamide (CPA) [23].
• In the colony assays, BSO increased the anti-cancer effects of the three chemotherapeutic agents, but did not modify the bone marrow suppression by CYM [24].
• Fos-IR in the spinal cord was not changed in rats receiving chronic CYP treatment (n = 15, 75 mg/kg, i.p., every 3rd day for 2 weeks) [14].
• Bladder afferent cells in the L6-S1 DRG labeled by Fluorogold (40 microliters) injected into the bladder wall did not exhibit NOS-IR in control animals; however, following chronic CYP administration, a significant percentage of bladder afferent neurons were NOS-IR: L6 (19.8 +/- 4.6%) and S1 (25.3 +/- 2.9%) [14].
• In control animals and in animals treated acutely with CYP, only small numbers of NOS-IR cells (0.5-0.7 cell profiles/sections) were detected in the L6-S1 dorsal root ganglia (DRG) [14].

Associations of cyclophosphamide with other chemical compounds

• Functional B1Rs were demonstrated by evoking ATP release and increases in [Ca(2+)](i) in CYP (24 h)-treated cultured rat urothelial cells with a selective B1 receptor agonist (des-Arg(9)-bradykinin) [4].
• A karyometric and stereologic study of the effects of gonadotrophin and testosterone on the interstitial gland of the testis of intact and endoxan treated rats [16].
• Reduced ovarian 32P uptake and a significantly decreased level of total gonadotrophin in the pituitary gland and serum were seen when fish were placed either in a drug concentration that had been found to kill half the fish in 96 h or in a safe concentration of Hexadrin and cythion in aquarium water [25].
• Male Wistar rats were treated with water, cyclophosphamide (CP) 40 mg/kg, and ribavirin 20, 100 and 200 mg/kg (i.p.) for 5 consecutive days at intervals of 24h [26].
• Since in vitro CY is inactive we have used in our experiments NM, a compound structurally and functionally related to phosphoramide mustard, the natural biologically active metabolite of CY [27].
• In 12 of 13 patient samples, increased DNA damage (gammaH2AX) was observed with clofarabine and cyclophosphamide compared with cyclophosphamide alone [28].
• The combination of veliparib with metronomic cyclophosphamide is well tolerated and shows promising activity in a subset of patients with BRCA mutations [29].

Gene context of cyclophosphamide

• In breast cancer, tumor MGMT expression was not predictive of response to CPM [30].
• At day 0 (Cy group), IL-1beta was expressed in selective intraislet macrophages but showed an increase from day 7 onwards in macrophages, a few beta cells, and somatostatin cells [31].
• In the Cy group a proportion of macrophages coexpressed IL-1beta and inducible nitric oxide synthase (iNOS) [31].
• The modifying effects of the aqueous extract of saffron (dried stigmas of Crocus sativus Linn.) on cisplatin (CIS), cyclophosphamide (CPH), mitomycin-C (MMC) and urethane (URE) induced alterations in lipid peroxidation and antioxidant status were investigated in Swiss albino mice [32].
• In ER-positive, premenopausal patients, there were no significant differences in RFS or OS among OVEX + TAM, MMC + CPA, TAM + MMC + CPA arms [33].
• We clarified that the single nucleotide polymorphisms in the promoter region or introns in the CYP2B6 affect the potency of cyclophosphamide activation to 4-hydroxycyclophosphamide [34].

Analytical, diagnostic and therapeutic context of cyclophosphamide

• Myeloablative conditioning (MC) was performed with Bu/cyclophosphamide (Cy)/etoposide (Eto) (n=4), Bu/Cy (n=2), and total body irradiation (TBI)/Cy/Eto (n=1) [35].
• CYP (24 h)-treated rats demonstrated bladder hyperactivity that was significantly reduced by intravesical administration of either B1 (des-Arg(10)-Hoe-140) or B2 (Hoe-140) receptor antagonists [4].
• Before TBI, conditioning chemotherapy consisted of cyclophosphamide (CY) alone (60 mg/kg per day on 2 successive days) in 24 patients, CY combined with other drugs in 6, and combinations without CY in 6 [36].
• Injection of CYP (n = 10, 75 mg/kg, i.p.) 2 hours prior to perfusion (acute treatment) of the animals increased Fos-immunoreactivity (IR) in neurons in the dorsal commissure, dorsal horn, and autonomic regions of spinal segments (L1-L2 and L6-S1) which receive afferent inputs from the bladder, urethra, and ureter [14].
• CY reduces CFU-S numbers, but the fraction synthesizing DNA can be either increased or decreased depending on time after treatment [37].

References