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11. Bonomi, P. D., Finkelstein, D. M., Ruckdeschel, J. C., Blum, R. H., Green, M. D., Mason, B., Hahn, R., Tormey, D. C., Harris, J., Comis, R., and Glick, J. Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. J. Clin. Oncol., 7: 16021613, 1989. Schiller, J. H., Cleary, J., and Johnson, D. Lung cancer: review of the ECOG experience. Oncology, 54: 353362, 1997. Schwartz, G. N., Pendyala, L., Kindler, H., Meropol, N., Perez, R., Raghavan, D., and Creaven, P. The clinical development of paclitaxel and the paclitaxel carboplatin combination. Eur. J. Cancer, 34: 1543 1548, Belani, C. P. Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer. Oncology, 12: 74 79, Schiller, J. H. Role of taxanes in lung-cancer chemotherapy. Cancer Investig., 16: 471 477, Belani, C. P., Natale, R. B., Lee, J. S., Socinski, M., Robert, F., Waterhouse, D., Rowland, K., Ansari, R. Lilenbaum, R., and Sridhar, K. Randomized phase III trial comparing cisplatin etoposide versus carboplatin paclitaxel in advanced and metastatic non-small cell lung cancer NSCLC ; . Proc. Am. Soc. Clin. Oncol., 17: 455a, 1998. Kelly, K., Crowley, J., Bunn, P. A., Livingston, R. B., and Gandara, D. R. A randomized phase III trial of paclitaxel plus carboplatin PC ; versus vinorelbine plus cisplatin VC ; in untreated advanced non-small cell lung cancer NSCLC ; : A Southwest Oncology Group SWOG ; trial. Proc. Am. Soc. Clin. Oncol., 18: 461A, 1999. Nitschke, R., Smith, E. I., Altshuler, G., Altmiller, D., Shuster, J., Green, A., Castleberry, R., Hayes, F. A., Golembe, B., and Ducos, R. Postoperative treatment of nonmetastatic visible residual neuroblastoma: a Pediatric Oncology Group study. J. Clin. Oncol., 9: 11811188, 1991. McWilliams, N. B., Hayes, F. A., Green, A. A., Smith, E. I., Nitschke, R., Altshuler, G. A., Shuster, J. J., Castleberry, R. P., and Vietti, T. J. Cyclophosphamide doxorubicin vs. cisplatin teniposide in the treatment of children older than 12 months of age with disseminated neuroblastoma: a Pediatric Oncology Group randomized Phase II study. Med. Pediatr. Oncol., 24: 176 180, Chen, A. R. High-dose therapy with hematopoietic rescue for children with solid tumors. In: M. C. Perry and D. Whippen eds. ; , American Society of Clinical Oncology Educational Book, 33rd Annual Meeting, pp. 144 153. Alexandria, VA: American Society of Clinical Oncology, 1997. 21. Haase, G. M., Perez, C., and Atkinson, J. B. Current aspects of biology, risk assessment, and treatment of neuroblastoma. Semin. Surg. Oncol., 16: 91104, 1999. Denekamp, J. Vascular attack as a therapeutic strategy for cancer. Cancer Metastasis Rev., 9: 267282, 1990. Kohn, E. C., and Liotta, L. A. Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res., 55: 1856 1862, Chabner, B. A., Boral, A. L., and Multani, P. Translational research: walking the bridge between idea and cure--seventeenth Bruce F. Cain memorial award lecture. Cancer Res., 58: 4211 4216, Pham, C. D., Roberts, T. P., van Bruggen, N., Melnyk, O., Mann, J., Ferrara, N., Cohen, R. L., and Brasch, R. C. Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor. Cancer Investig., 16: 225230, 1998. Prewett, M., Huber, J., Li, Y., Santiago, A., O'Connor, W., King, K., Overholser, J., Hooper, A., Pytowski, B., Witte, L., Bohlen, P., and Hicklin, D. J. Antivascular endothelial growth factor receptor fetal liver kinase 1 ; monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res., 59: 5209 5218, Benjamin, L. E., Goliganin, D., Itin, A., Pode, D., and Keshet, E. Selective ablation of immature blood vessels in established human.
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A retirement party is being organised for Malcolm Aiken, MRPharmS, admissions tutor at the University of Brighton School of Pharmacy and Biomolecular Sciences, at the Mezz restaurant, Lewes Road, Brighton on 30 September. A portfolio of memories is also being organised. For details, or to contribute to the portfolio or the fund for leaving gifts, contact the pharmacy school office on 01273 642014 e-mail PabsSchoolOffice brighton.ac.
19. Szanto, A., Narkar, V., Shen, Q., Uray, I.P., Davies, P.J. and Nagy, L. 2004 ; Retinoid X receptors: X-ploring their patho ; physiological functions. Cell Death Differ., 11 Suppl. 2 ; , S126S143. 20. Huang, J., Powell, W.C., Khodavirdi, A.C., Wu, J., Makita, T., Cardiff, R.D., Cohen, M.B., Sucov, H.M. and Roy-Burman, P. 2002 ; Prostatic intraepithelial neoplasia in mice with conditional disruption of the retinoid X receptor alpha allele in the prostate epithelium. Cancer Res., 62, 48124819. 21. Li, M., Indra, A.K., Warot, X., Brocard, J., Messaddeq, N., Kato, S., Metzger, D. and Chambon, P. 2000 ; Skin abnormalities generated by temporally controlled RXRalpha mutations in mouse epidermis. Nature, 407, 633636. 22. Li, M., Chiba, H., Warot, X., Messaddeq, N., Gerard, C., Chambon, P. and Metzger, D. 2001 ; RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations. Development, 128, 675688. 23. Mao, G.E., Reuter, V.E., Cordon-Cardo, C., Dalbagni, G., Scher, H.I., DeKernion, J.B., Zhang, Z.F. and Rao, J. 2004 ; Decreased retinoid X receptor-alpha protein expression in basal cells occurs in the early stage of human prostate cancer development. Cancer Epidemiol. Biomarkers Prev., 13, 383390. 24. Li, H., Kolluri, S.K., Gu, J. et al. 2000 ; Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science, 289, 11591164. 25. Heyman, R.A., Mangelsdorf, D.J., Dyck, J.A., Stein, R.B., Eichele, G., Evans, R.M. and Thaller, C. 1992 ; 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell, 68, 397406. 26. de Urquiza, A.M., Liu, S., Sjoberg, M., Zetterstrom, R.H., Griffiths, W., Sjovall, J. and Perlmann, T. 2000 ; Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science, 290, 21402144. 27. Lengqvist, J., Mata De Urquiza, A., Bergman, A.C., Willson, T.M., Sjovall, J., Perlmann, T. and Griffiths, W.J. 2004 ; Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain. Mol. Cell. Proteomics, 3, 692703. 28. Goldstein, J.T., Dobrzyn, A., Clagett-Dame, M., Pike, J.W. and DeLuca, H.F. 2003 ; Isolation and characterization of unsaturated fatty acids as natural ligands for the retinoid-X receptor. Arch Biochem. Biophys, 420, 185193. 29. Khuri, F.R., Rigas, J.R., Figlin, R.A. et al. 2001 ; Multi-institutional phase I II trial of oral bexarotene in combination with cisplatin and vinorelbine in previously untreated patients with advanced non-small-cell lung cancer. J. Clin. Oncol., 19, 26262637. 30. Lemotte, P.K., Keidel, S. and Apfel, C.M. 1996 ; Phytanic acid is a retinoid X receptor ligand. Eur. J. Biochem., 236, 328333. 31. Kitareewan, S., Burka, L.T., Tomer, K.B. et al. 1996 ; Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR. Mol. Biol. Cell, 7, 11531166. 32. Kolluri, S.K., Corr, M., James, S.Y., Bernasconi, M., Lu, D., Liu, W., Cottam, H.B., Leoni, L.M., Carson, D.A. and Zhang, X.K. 2005 ; The R-enantiomer of the nonsteroidal antiinflammatory drug etodolac binds retinoid X receptor and induces tumor-selective apoptosis. Proc. Natl Acad. Sci. USA, 102, 25252530. 33. Prufer, K. and Barsony, J. 2002 ; Retinoid X receptor dominates the nuclear import and export of the unliganded vitamin D receptor. Mol. Endocrinol., 16, 17381751. 34. Lin, X.F., Zhao, B.X., Chen, H.Z., Ye, X.F., Yang, C.Y., Zhou, H.Y., Zhang, M.Q., Lin, S.C. and Wu, Q. 2004 ; RXR acts as a carrier for TR3 nuclear export in a 9-cis retinoic acid-dependent manner in gastric cancer cells. J. Cell Sci., 117, 56095621. 35. Dufour, J.M. and Kim, K.H. 1999 ; Cellular and subcellular localization of six retinoid receptors in rat testis during postnatal development: identification of potential heterodimeric receptors. Biol. Reprod., 61, 13001308. 36. Boulogne, B., Levacher, C., Durand, P. and Habert, R. 1999 ; Retinoic acid receptors and retinoid X receptors in the rat testis during fetal and postnatal development: immunolocalization and implication in the control of the number of gonocytes. Biol. Reprod., 61, 15481557. 37. Katagiri, Y., Takeda, K., Yu, Z.X., Ferrans, V.J., Ozato, K. and Guroff, G. 2000 ; Modulation of retinoid signalling through NGF-induced nuclear export of NGFI-B. Nat. Cell Biol., 2, 435440. 38. Casas, F., Daury, L., Grandemange, S., Busson, M., Seyer, P., Hatier, R., Carazo, A., Cabello, G. and Wrutniak-Cabello, C. 2003 ; Endocrine regulation of mitochondrial activity: involvement of truncated RXRalpha and c-ErbA alpha1 proteins. FASEB J., 17, 426436.
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5. Robieux I, Sorio R, Galligioni E et al. Pharmacokinetics of vinorelbine in elderly patients with metastatic breast cancer. Ann Oncol 1994; 5 Suppl 8 ; : 58. 6. Colleoni M, Gaion F, Nelli P et al. Weekly vinorelbine in elderly patients with non-small-cell lung cancer. Tumori 1994; 80: 448 Veronesi A, Crivellari D, Magri MD et al. Vinorelbine treatment of advanced non-small-cell lung cancer with special emphasis on elderly patients. Eur J Cancer 1996; 32: 1809 Blum JL, Buzdar AU, Lo Russo et al. A multicenter phase II trial of Xelodae capecitabine ; in paclitaxel-refractory metastatic breast cancer. Proc Soc Clin Oncol 1998; 17: 125a Abstr 476 ; . 9. O'Reilly SM, Moiseyenko V, Talbot DC et al. A randomized phase II study of Xelodae capecitabine ; vs paclitaxel in breast cancer patients failing previous anthracycline therapy. Proc Soc Clin Oncol 1998; 17: 163a Abstr 627 ; . 10. O'Shaughnessy J, Moiseyenko V, Bell D et al. A randomized phase II study of Xelodae capecitabine ; vs CMF as first line chemotherapy of breast cancer in women aged more than 55 years. Proc Soc Clin Oncol 1998; 17: 103a Abstr 398 ; . 11. Khoury P, Villalona-Calero M, Blum J et al. Phase I study of capecitabine in combination with paclitaxel in patients with previously treated metastatic breast cancer. Proc Soc Clin Oncol 1998; 17: 206a Abstr 793 ; . 12. Pronk L, Vasey PA, Sporreboom A et al. A matrix-designed phase I dose-finding and pharmacokinetic study of the combination of Xelodae plus Taxoteree. Proc Soc Clin Oncol 1998; 17: 212a Abstr 816 ; . 13. Dieras V, Extra JM, Bellisant E et al. Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer: results of a phase II study using a sequential group method. J Clin Oncol 1996; 14: 30973104. ` 14. Nole F, De Braud F, Aapro MS et al. Phase I II study of vinorelbine in combination with 5-fluorouracil and folinic acid as first-line chemotherapy in metastatic breast cancer: a regimen with a low subjective toxic burden. Ann Oncol 1997; 8: 865870. Berruti A, Sperone P, Bottini A et al. Phase I study of vinorelbine with protracted fluorouracil infusion as second- or third-line approach for advanced breast cancer patients previously treated with anthracyclines. J Clin Oncol 2000; 18: 33703377. Kattan J, Marwan G, Fadi F et al. Phase I study of vinorelbine and capecitabine combination as first line treatment of metastatic breast cancer. Ann Oncol 2002; 13 Suppl 5 ; : 56 Abstr 201P ; . 17. Welt A, von Minckwitz G, Borquez D et al. Capecitabine in combination with vinorelbine in pretreated patients with metastatic breast cancer--results of an extended phase II study. Ann Oncol 2002; 13 Suppl 5 ; : 56 Abstr 202P.
Mechanisms of action. Their use may allow for novel approaches to second-line chemotherapy for recurrent NSCLC 2, 3 ; . The combination regimens of these agents with a platinum compound are considered as the standard first-line treatment based on results of recent phase III studies 4, 5 ; . Two recent randomized studies have demonstrated that second-line docetaxel prolonged the survival and clinical benefit, as well as improved the quality of life compared with best supportive care 6 ; or monotherapy with vinorelbine or ifosfamide 7 ; . However, these benefits of docetaxel are limited. The most common first-line combined regimen is platinum and taxane paclitaxel or docetaxel ; 4 ; . If taxane is used as the first-line treatment, there is no consensus on the optimum second-line and viracept.
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1. Rahman ZU, Frye DK, Smith TL, Asmar L, Theriault RL, Buzdar AU, Hortobagyi GN: Results and long-term followup for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy. Cancer, 85: 104-111, 1999. Biganzoli L, Piccart MJ: The bigger the better?. or what we know and what we still need to learn about anthracycline dose per course, dose density and cumulative dose in the treatment of breast cancer. Ann Oncol, 8: 1177-1182, 1997. Riccardi A, Tinelli C, Brugnatelli S, Pugliese P, Giardina V, Giordano M, Danova M, Richetti A, Fava S, Rinaldi E, Fregoni V, Trotti G, Poli A: Doubling the epirubicin dosage in the 5-fluorouracil, epirubicin and cyclophosphamide FEC ; regimen for advanced breast cancer: a prospective, randomized, multicentric study on antitumor effect and life quality. Int J Oncol, 16: 769-776, 2000. Muss HB, Case LD, Richards F 2nd, White DR, Cooper MR, Cruz JM, Powell BL, Spurr CL, Capizzi RL: Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. N Engl J Med, 325: 1342-1348, 1991. Falkson G, Gelman RS, Pandya KJ, Osborne CK, Tormey D, Cummings FJ, Sledge GW, Abeloff MD: Eastern Cooperative Oncology Group randomized trial of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment. J Clin Oncol, 16: 1669-1676, 1998. Alba E, Martin M, Ramos M, Adrover E, Balil A, Jara C, Barnadas A, Fernandez-Aramburo A, Sanchez-Rovira P, Amenedo M, Casado A; Spanish Breast Cancer Research Group: Multicenter randomized trial comparing sequential with concomitant administration of doxorubicin and docetaxel as first-line treatment of metastatic breast cancer: a Spanish Breast Cancer Research Group GEICAM-9903 ; phase III study. J Clin Oncol, 22: 2587-2593, 2004. Hochster HS, Vogel CL, Burman SL, White R: Activity and safety of vinorelbine combined with doxorubicin or fluorouracil as first-line therapy in advanced breast cancer: a stratified phase II study. Oncologist, 6: 269-277, 2001.
Analysis of Tissue Metal Levels Tissue sections of brain, liver, and sciatic nerve were analyzed by inductively coupled plasma-atomic emission spectroscopy ICP-AES ; at the Diagnostic Center for Population and Animal Health at Michigan State University East Lansing, MI ; . Elements determined in this analysis were copper, calcium, iron, and zinc. Individual liver and brain samples were analyzed in duplicate for mineral content and the results reported as one value per individual. One sciatic nerve was taken from each animal and pooled with other members of the same treatment group to provide adequate tissue for ICP-AES analysis; and this resulted in one analysis injected twice per group thus generating two values per group. Brain tissue samples for ICP-AES were approximately 2 mm mid-sagittal slices; liver sections were approximately 1cm3 pieces of tissue; sciatic nerve sections were approximately 15-20 mm lengths of a single nerve and viread.
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Figure C. neoformans cfu after incubation with J774.16 in the presence and absence of monoclonal antibody 2H1 and 5-flucytosine 5-FC ; . P, refers to comparison with the J774.16 group; P2 refers to comparison with the J774.16 + monoclonal antibody 2H1 group; Ps refers to comparison with the J774.16 + 5-flucytosine group.
Pharmacokinetics of vinorelbine are not influenced by the concurrent and vistaril.
Peggs K, Verfuerth S, Mackinnon S. Induction of cytomegalovirus CMV ; -specific T-cell responses using dendritic cells pulsed with CMV antigen: a novel culture system free of live CMV virions. Blood. 2001; 97: 994-1000.
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Shift against lefties L-15 ; , but it's that righty shift that will be killing Hudson's opponents. Two other cards jump out of the pile: Derek Jeter 3 0s, 11 hits, 4 walks, 29 SSN for 19 attempts ; and Jeff Kent 1-0-0-0, 10 hits, 4 walks ; man the middle of the infield and buttress the lineup. Kent came over from Maracaibo, who bludgeoned the league with him all last season. Three other guys are in the lineup to hit for distance. Jason Lane 1-4-5-6, 10 hits, 2 walks ; has a nice singlecolumn card, and bats fifth and sixth all year. Wily Mo Pea 1-1-6-6, 9 hits, 2 walks ; had a card like this last year and barely hit at all. You gotta love the double-1s, though. Ivan Rodriguez 4 0s, 10 hits, 3 31s ; bats ninth all year. Matt Stairs 1-6-6, 9 hits, 5 walks ; probably has a better card than any of these guys, but was denied the magic fourth power number by the Game Company. Still, he bats in the middle of most lineups. The table setters are Luis Castillo 2 0s, 10 hits, 4 walks ; , with a little help from Damian Jackson 2 0s, 10 hits, 3 walks ; . Cory Sullivan 2 0s, 11 hits, 2 walks ; helps out on the boards. There are five regulars with 14 on-base numbers or more, five with four power numbers, three with 11 hits. It does not look like this team will struggle to score runs like last year's outfit.
Injection site reactions: Vinorelbine is a moderate vesicant and can produce extravasation injury eg, considerable irritation, local tissue necrosis and or thrombophlebitis ; . Injection site reactions occur in about one-third of patients, of which 2% were severe. Reactions include erythema, pain at injection site, vein discoloration, localized rash and urticaria. Chemical phlebitis proximal to the injection site has been reported. The occurrence and severity of venous irritation appear to be reduced when vinorelbine is given as a 6-10 minute infusion with a free-flowing IV fluid and 3, 20, 21 Phlebitis occurs in approximately 5-10% of flushing with at least 75-125 mL NS or D5W after administration. patients; however, the frequency of phlebitis was notably greater in clinical trials in which vinorelbine was administered over one hour.4 A heat pad on the distal vein may help to minimize injection site reactions.2 22, 23 Hydrocortisone 100 mg IV may be given prior to vinorelbine if the patient experiences pain on administration. Acute dyspnea and severe bronchospasm occur infrequently. The acute reaction resembles an allergic event 3 and may respond to bronchodilators. Risk factor includes concurrent use of mitomycin. Subacute pulmonary reactions occur within one hour after drug administration and may be characterized by cough, dyspnea, hypoxemia and interstitial infiltration. Subacute pulmonary reactions may respond to corticosteroid therapy. Oxygen may provide symptomatic relief.3, 24 Neuropathy: Mild to moderate peripheral neuropathy paresthesia, hypesthesia ; is the most frequently reported 3 neurologic toxicity and usually reversible on discontinuation of vinorelbine. Cisplatin does not appear to increase the neurotoxic effects of vinorelbine. However, prior treatment with paclitaxel may result in cumulative neurotoxicity.4 Alopecia manifests as gradual hair thinning, but total hair loss is uncommon and voriconazole.
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Combination chemotherapy has been shown to improve overall survival compared with best supportive care in patients with advanced non-small cell lung cancer NSCLC ; . The survival advantage is modest and was initially demonstrated with cisplatin-containing regimens in a large meta-analysis of randomized trials reported in 1995. Newer chemotherapy combinations have been shown to be better tolerated than older cisplatin-based combinations, and some trials have also shown greater efficacy and survival benefits with these newer combinations. Combination chemotherapy is, therefore, the currently accepted standard of care for patients with good performance statuses aged less than 70 years with advanced NSCLC. However, there are limited data from clinical trials to support the use of combination chemotherapy in elderly patients over 70 years of age with advanced NSCLC. Subgroup analyses of large randomized phase III trials suggest that elderly patients with good performance statuses do as well as younger patients treated with combination chemotherapy. There are few randomized trials reported that evaluate chemotherapy in patients aged greater than 70 years only. Based on data from trials performed by an Italian group, single-agent vinorelbine has been shown to have significant activity in elderly patients with advanced NSCLC and to be well tolerated by those patients with Eastern Cooperative Oncology Group performance statuses of two or less, with associated improvements in measures of global health. The Oncologist 2003; 8: 270-277.
2.2. Theorem. If P is poly-bicategory that has tensors, pars and their units, then its objects, 1-cells and 2-cells together with the chosen data form a linear bicategory B in the sense of [6]. Proof. In the one-object case, this is in the original paper on linearly distributive categories [7], and the general proof is essentially the same. We just mention that CQ f cutting appropriate tensor and par links induces poly-2-cells f, g h g, h and CQ f, g h whenever D1 f D0 and D1 g D0 Under the inverse bijections f g, h of and its dual, these yield the "linear distributivities" f g h and vortex.
Prognostic Implications of Abnormalities in Renal Function in Patients With Acute Coronary Syndromes Jassim Al Suwaidi, Donal N. Reddan, Kathryn Williams, Karen S. Pieper, Robert A. Harrington, Robert M. Califf, Christopher B. Granger, E. Magnus Ohman, David R. Holmes, Jr and for the GUSTO-IIb, GUSTO-III, PURSUIT, and PARAGON-A Investigators Circulation 2002; 106; 974-980; originally published online Aug 12, 2002; DOI: 10.1161 01.CIR.0000027560.41358.B3 and vinorelbine.
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