Cumulative Contents, 1983

Total Page:16

File Type:pdf, Size:1020Kb

Cumulative Contents, 1983 Cumulative Contents, 1983 Volume 47, No.1 January 1983 I STEEL, G.G., COURTENAY, V.D. & OXFORD LYMPHOMA GROUP. Prognostic PECKHAM, M.J. The response to chemotherapy factors in non-Hodgkins lymphoma: The of a variety of human tumour xenografts. importance of symptomatic stage as an adjunct to the Kiel histopathological classification. 15 STRUCK, R.F., DYKES, D.J., CORBETT, T.H., SULING, W.J. & TRADER, M.W. 103 TRENT, J.M., DAVIS, J.R. & DURIE, B.G.M. Isophosphoramide mustard, a metabolite of Cytogenetic analysis of leukaemic colonies from ifosfamide with activity against murine tumours acute and chronic myelogenous leukaemia. comparable to cyclophosphamide. Ill CHILD, J.A., CRAWFORD, S.M., NORFOLK, 27 MUINDI, J.R.F., NEWELL, D.R., SMITH, I.E. D.R., O'QUIGLEY, J., SCARFFE, J.H. & & HARRAP, K.R. Pentamethylmelamine STRUTHERS, L.P.L. Evaluation of serum beta (PMM): Phase I clinical and pharmacokinetic 2-microglobulin as a prognostic indicator in studies. myelomatosis. 35 FORD, C.H.J., NEWMAN, C.E., JOHNSON, 115 EL-DEEB, B.B., BURNS, S., ROBINSON, R., J.R., WOODHOUSE, C.S., ROWLAND, G.F., HAMMOND, E.M. & MANN, J.R. Serum SIMMONDS, R.G. & REEDER, T.A. dopamine-,B-hydroxylase in children with Localisation and toxicity study of a vindesine neuroblastoma. anti-CEA conjugate in patients with advanced cancer. 123 BINDON, C., CZERNIECKI, M., RUELL, P.. EDWARDS, A., McCARTHY, W.H.. 43 EMBLETON, M.J., ROWLAND, G.F., HARRIS, R. & HERSEY, P. Clearance of rates SIMMONDS, R.G., JACOBS, E., MARSDEN, and systematic effects of intravenously C.H. & BALDWIN, R.W. Selective cytotoxicity administered Interleukin 2 (IL2) containing against human tumour cells by a vindesine- preparations in human subjects. monoclonal antibody conjugate. 135 SIKORA, K., ALDERSON, T. & ELLIS, J. 51 BEN-HUR, E., SHAW, J.J. & BLEEHEN, N.M. Human hybridomas from patients with malignant Enhancement of thermal killing by polyamines V. disease. The response of EMT6 multicellular tumour spheroids versus monolayer cells. 147 VAN DE LINDE, A.W., STREEFKERK, M., SCHUURMAN, H.J., TE VELDE, E.R. & 57 TWENTYMAN, P.R. Modification by WR 2721 KATER, L. Divergence between the occurrence of the response to chemotherapy of tumours and of antibody and cellular immune reactivity to normal tissues in the mouse. cervical carcinoma cell lines in preinvasive and macroinvasive stages of cervical carcinoma. 65 ROJAS, A., STEWART, F.A. & DENEKAMP, J. Interaction of misonidazole and WR-2721. 2. 155 ASTOR, M.B., PARHAM, J.C., HALL, E.J., Modification of tumour radiosensitization. TEMPLETON, M.A. & HARTOG, B. A 3-nitro triazole as a hypoxic cell sensitizer. 73 ANDO, K., PETERS, L.J., HUNTER, N., JINNOUCHI, K. & MATSUMOTO, T. 158 ROSSOWSKI, W. & SAHAI SRIVASTAVA, Inhibition of artificial and spontaneous lung B.I. Ectosialyltransferase activity: a marker for metastases by preirradiation of abdomen II. certain human haematopoietic cells. Target organ and mechanism. 161 WALKER, L.C., TUCKER, D.F. & BEGENT, 81 WEISS, L., HOLMES, J.C. & WARD, P.M. Do R.H.J. Identification of PEG-precipitable serum metastases arise from pre-existing subpopulations factor associated with malignant lymphoma as C- of cancer cells? reactive protein. 91 LEONARD, R.C.F., CUZICK, J., 165 BOOK REVIEWS MACLENNAN, I.C.M., VANHEGAN, R.I., MACKIE, P.H., McCORMICK, C.V. & 167 ANNOUNCEMENTS Volume 47, No. 2 February 1983 175 IJIRI, K. & POTTEN, C.S. Response of 269 SECRETO, G., RECCHIONE, C., intestinal cells of differing topographical and CAVALLERI, A., MIRAGLIA, M. & DATI, V. hierarchical status to ten cytotoxic drugs and five Circulating levels of testosterone, 17f,-oestradiol sources of radiation. luteinising hormone and prolactin in postmenopausal breast cancer 187 TWENTYMAN, P.R. & WORKMAN, P. An patients. investigation of the possibility of 277 TOMLEY, F.M., ARMSTRONG, S.J., MAHY, chemosensitization by clinically achievable B.W.J. & OWEN, L.N. Reverse transcriptase concentrations of misonidazole. activity and particles of retroviral density in cultured canine lymphosarcoma supernatants. 195 MURRAY, D. & MEYN, R.E. Enhancement of the DNA cross-linking activity of melphalan by 285 MOLE, R.H., PAPWORTH, D.G. & CORP, misonidazole in vivo. M.J. The dose-response for X-ray induction of myeloid leukaemia in male CBA/H mice. 205 MORGAN, D., FRESHNEY, R.I., DARLING, J.L., THOMAS, D.G.T. & CELIK, F. Assay of 293 TISDALE, M.J. & BRENNAN, R.A. Loss of anticancer drugs in tissue culture: cell cultures of acetoacetate coenzyme A transferase activity in biopsies from human astrocytoma. tumours of peripheral tissues. 215 EVANS, B.D., SMITH, I.E. & MILLAR, J.L. High dose cyclophosphamide treatment of human oat cell xenografts in immune deprived mice. Short Communications 221 SILVESTRINI, B., HAHN, G.M., CIOLI, V. & 299 MORIYAMA, S., KAWAOI, A. & HIROTA, N. DE MARTINO, C. Effects of lonidamine alone Gamma-glutamyl transpeptidase in putative or combined with hyperthermia in some precancerous thyroid lesions of rats treated with experimental cell and tumour systems. diisopropanolnitrosamine. 303 PINKERTON, C.R. Is folate absorption 233 HASTINGS, R.J. & FRANKS, L.M. Cellular impaired by high dose methotrexate? heterogeneity in a tissue culture cell line derived from a human bladder carcinoma. 307 MCCLUSKEY, D.R., ROY, A.D., ABRAM, W.P. & MARTIN, W.M.C. T lymphocyte subsets 245 KERR, K.M., ROBERTSON, A.M.G. & in the peripheral blood of patients with benign LAMB, D. In vitro thymidine labelling of human and malignant breast disease. pulmonary neoplasms. 311 SWERDLOW, A.J. Epidemiology of melanoma 253 SMEDLEY, H.M., FINAN, P., LENNOX, E.S., of the eye in the Oxford region, 1952-1978. RITSON, A., SIKORA, K. TAKEI, F. & WRAIGHT, P. Localisation of metastatic carcinoma by a radio-labelled monoclonal Letter to the Editor antibody. 315 KAY, H.E.M. Planning and comparisons in 261 CASTAGNETTA, L., LO CASTO, M., clinical trials. MERCADANTE, T., POLITO, L., COWAN, S. & LEAKE, R.E. Intra-tumoural variation of 319 BOOK REVIEWS oestrogen receptor status in endometrial cancer. 323 ANNOUNCEMENTS Volume 47, No.3 March 1983 327 HABESHAW, J.A., BAILEY, D., STANSFELD, 361 JONES, D.H., BLEEHEN, N.M., SLATER, A.G. & GREAVES, M.F. The cellular content of A.J., GEORGE, P.J.M., WALKER, J.R. & non Hodgkin lymphomas: Comprehensive analysis DIXON, A.K. Human lymphoblastoid interferon using monoclonal antibodies and other surface in the treatment of small cell lung cancer. marker techniques. 367 BURTIN, C., NOIROT, C., PAUPE, J. & 353 TESTORELLI, C., CANTI, G., FRANCO, P., SCHEINMANN, P. Decreased blood histamine GOLDIN, A. & NICOLIN, A. Serotherapy of levels in patients with solid malignant tumours. L 1210 murine leukaemia-reasons for ineffectiveness of in vivo treatment by L. 1 monoclonal antibody. Short Communications 373 BRATTAIN, M.G., MARKS, M.E., 419 ROHATINER, A.Z.S., PRIOR, P.F., BURTON, McCOMBS, J., FINELY, W. & BRATTAIN, A.L., SMITH, A.T., BALKWILL, F.R. & D.E. Characterisation of human colon carcinoma LISTER, T.A. Central nervous system toxicity of cell lines isolated from a single primary tumour. interferon. 383 BIGGAR, R.J., CURTIS, R.E., HOFFMAN, D. 423 JEHN, U., KERN, D., WACHHOLZ, K. & & FLANNERY, J.T. Second primary HOLZEL, D. Prognostic value of in vitro growth malignancies following salivary gland cancers. pattern of colony forming cells in adult acute leukaemia. 387 DURAND, R.E. Radioprotection by WR-2721 in vitro at low oxygen tensions: Implications for its 429 MILLER, W.R., STURGEON, C.M. & mechanism of action. WALKER, R.A. Carcinoembryonic antigen (CEA) in explants of human breast cancer: 393 PHEASANT, A.E., BATES, J., BLAIR, J.A. & Comparison of immunohistochemical detection NAYYIR-MAZHIR, R. Investigations of tissue and release short-term culture. folates in normal and malignant tissues. during 433 MORRIS, I.D. & STEPHEN, T.M. In vitro and 399 SIDEBOTTOM, E. & CLARK, S.R. Cell fusion in vivo interactions of methotrexate and other segregates progressive growth from metastases. antimetabolites with the oestrogen high affinity 407 OOSTERHUIS, J.W., BAGASRA, O., receptors of the rat uterus. KUSHNER, H., FOX, N. & DAMJANOV, I. 439 TERASIMA, T., YASUKAWA, M. & The effects of regional factors on the growth rate KIMURA, M. Development of insusceptibility to and the differentiation of mouse teratocarcinoma. serum factor during the radiation transformation 413 PRIME, S.S., MACDONALD, D.G. & RENNIE, process. J.S. The effect of iron deficiency on experimental 443 BOOK REVIEWS oral carcinogenesis in the rat. 447 ANNOUNCEMENTS Volume 47, No. 4 April 1983 455 VESSEY, M., BARON, J., DOLL, R., 503 BOCIAN, E., LAVERICK, M. & NIAS, A.H.W. McPHERSON, K. & YEATES, D. Oral The mode of action of cis-dichloro-bis contraceptives and breast cancer: Final report of (isopropylamine) trans dihydroxy platinum IV- an epidemiological study. (CHIP) studied by the analysis of chromosome 463 DURBEC, J.P., CHEVILLOTTE, G., BIDART, aberration production. J.M., BERTHEZENE, P. & SARLES, H. Diet, 511 HARLAND, R.N.L., BARNES, D.M., alcohol, tobacco and risk of cancer of the pancreas: A HOWELL, A., RIBEIRO, G.G., TAYLOR, J. & case-control study. SELLWOOD, R.A. Variation of receptor status 471 VAN STEENSEL-MOLL, H.A., in cancer of the breast. VALKENBURG, H.A. & VAN ZANEN, G.E. Incidence of childhood leukaemia in the 517 BARBASON, H., RASSENFOSSE, C. & BETZ, Netherlands (1973-1980). E.H. Promotion mechanism of phenobarbitol and partial hepatectomy in DENA hepato- 477 BLEWITT, R.W., ABBOTT, A.C. & BIRD, C.C. carcinogenesis cell kinetics effect. Mode of cell death induced in human lymphoid cells by high and low doses of glucocorticoid. 527 KOCH, G.L.E. & SMITH, M.J. Concanavalin A 487 acceptor glycoproteins: A new type of marker for GRONOWITZ, J.S., HAGBERG, H., the classification of KALLANDER, C.F.R. & SIMONSSON, B. The tumour cells. use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of Short Communications patients with non-Hodgkin's lymphoma.
Recommended publications
  • Information to Users
    INFORMATION TO USERS This manuscript has been reproduced from the microfihn master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type o f computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand comer and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6” x 9” black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. UMI A Bell & Howell Infomiation Company 300 North Zed) Road, Ann Arbor MI 48106-1346 USA 313/761-4700 800/521-0600 i j DEVELOPMENT OF DRUGS FOR HUMAN PROSTATE CANCER DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Chiung-Tong Chen, M.S.
    [Show full text]
  • Induction of Dormancy in Hypoxic Human Papillomavirus-Positive Cancer Cells
    Induction of dormancy in hypoxic human papillomavirus-positive cancer cells Karin Hoppe-Seylera, Felicitas Bosslera, Claudia Lohreya, Julia Bulkeschera, Frank Röslb, Lars Jansenc, Arnulf Mayerd, Peter Vaupeld, Matthias Dürstc, and Felix Hoppe-Seylera,1 aMolecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany; bViral Transformation Mechanisms (F030), German Cancer Research Center, D-69120 Heidelberg, Germany; cDepartment of Gynecology, Jena University Hospital, D-07743 Jena, Germany; and dDepartment of Radiooncology and Radiotherapy, Mainz University Medical Center, D-55131 Mainz, Germany Edited by Karl Münger, Tufts University School of Medicine, Boston, MA, and accepted by Editorial Board Member Peter K. Vogt December 19, 2016 (received for review September 21, 2016) Oncogenic human papillomaviruses (HPVs) are closely linked to major (17), is considered to play a major role in tumor development and human malignancies, including cervical and head and neck cancers. It progression. Clinically, hypoxia can increase the resistance to is widely assumed that HPV-positive cancer cells are under selection chemotherapy and radiotherapy and is a negative prognostic pressure to continuously express the viral E6/E7 oncogenes, that their marker for many cancers, including HPV-positive tumors (15, 16, intracellular p53 levels are reconstituted on E6/E7 repression, and that 18–20). Notably, although O2 availability is known to affect tumor E6/E7 inhibition phenotypically results in cellular senescence. Here we cell biology (14–16), most functional studies of the HPV E6/E7 show that hypoxic conditions, as are often found in subregions of oncogenes in cervical cancer cells have been performed under cervical and head and neck cancers, enable HPV-positive cancer cells to standard cell culture conditions at 21% O2.
    [Show full text]
  • The Role of Pik3ca in Head and Neck Cancer Progression
    THE ROLE OF PIK3CA IN HEAD AND NECK CANCER PROGRESSION by XI CHEN B.S., The University of Denver, 2010 A thesis submitted to the Faculty of the Graduate School of the University of Colorado in partial fulfillment of the requirements for the degree of Doctor of Philosophy Cancer Biology Program 2016 This thesis for Doctor of Philosophy degree by Xi Chen has been approved for the Cancer Biology Program by Rebecca Schweppe, Chair Mary Rayland Lynn Heasley Heide Ford Maranke Koster Shi-long Lu, Advisor Date: December 16, 2016 ii Xi Chen (Ph.D., Cancer Biology) The Role of PIK3CA in Head and Neck Cancer Progression Thesis directed by Professor Shi-long Lu ABSTRACT Head and neck squamous cell carcinoma (HNSCC) patients have a poor prognosis, with invasion, recurrence and metastasis as major causes of mortality. Currently, effective therapeutic options for advanced HNSCCs are still limited. The phosphatidylinositol 3-kinase (PI3K) pathway regulates a wide range of cellular processes crucial for tumorigenesis, and PIK3CA amplification and mutation are among the most common genetic alterations in HNSCC. Compared to the well- documented roles of the PI3K pathway in cell growth and survival, its roles in tumor invasion, recurrence and metastasis have not been well delineated. Herein, I used a PIK3CA-genetically engineered mouse model (PIK3CA- GEMM) in which PIK3CA is overexpressed in head and neck epithelium to mimic PIK3CA amplification in human HNSCC patients. I found that PIK3CA overexpression increased tumor invasiveness and metastasis by increasing de- differentiation and epithelial-to-mesenchymal transition (EMT), and marked inflammation in tumor stroma.
    [Show full text]
  • Combined Inhibition of Mtor and Pikks Exploits Replicative and Checkpoint Vulnerabilities to Induce Death of PI3K-Activated Triple-Negative Breast Cancer Cells
    bioRxiv preprint doi: https://doi.org/10.1101/700625; this version posted July 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Combined inhibition of mTOR and PIKKs exploits replicative and checkpoint vulnerabilities to induce death of PI3K-activated triple-negative breast cancer cells Sameer S. Chopra,1,3,5 Anne Jenney,1,3 Adam Palmer,1,3 Mario Niepel,1,3 Mirra Chung,1,3 Caitlin Mills,1,3 Sindhu Carmen Sivakumaren,2,5 Qingsong Liu,2,5 Jia-Yun Chen,1 Clarence Yapp,1,3 John M. Asara,4 Nathanael S. Gray,2,5 Peter K. Sorger1,3* 1Laboratory of Systems Pharmacology, 2Dept. of Biological Chemistry and Molecular Pharmacology, 3Harvard Ludwig Center, 4Division of Signal Transduction, Beth Israel Deaconess Medical Center, 5Dana-Farber Cancer Institute Harvard Medical School, 200 Longwood Avenue, Boston, MA 02215 *Corresponding: [email protected] Page 1 bioRxiv preprint doi: https://doi.org/10.1101/700625; this version posted July 12, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. SUMMARY Frequent mutation of genes in the PI3K/AKT/mTOR signaling pathway in human cancers has stimulated large investments in therapeutic drugs but clinical successes have been rare.
    [Show full text]
  • Mistletoe Therapy
    The Journal of IHP – Continuing Education SUCCESSFUL COMPLETION OF THE QUESTIONS AT THE END OF THIS PAPER HAS BEEN APPROVED FOR CONTINUING EDUCATION BY THE BDDT-N; 1.0 CREDIT PARENTAL THERAPY AND BY THE CNPBC; ONE CE HOUR. Mistletoe Therapy Improving Outcomes In Complementary Cancer Care By Sarah Vanderheyden, RPN and Heidi Fritz, MA, ND Sarah Vanderheyden, RPN ABSTRACT: 8 Leland Road, London, ON N6K Mistletoe therapy is an herbal medicine best known for its role in complementary 1T1 cancer care. Pioneered by Rudolf Steiner, mistletoe, also known as Viscum album L or European mistletoe, has its roots in anthroposophic medicine; today there is Heidi Fritz, MA, ND a large body of evidence supporting use of mistletoe injection therapy as an Bolton Naturopathic Clinic, adjunctive cancer treatment. Lectins and viscotoxins found in mistletoe appear to 64 King Street West, Bolton, ON, L7E 1C7 www. be responsible for its antitumor and immune stimulating effects. Mistletoe boltonnaturopathic.ca therapy has been investigated for its effects on survival, quality of life, and tolerability of chemotherapy/ side effects associated with chemotherapy. Meta analyses and systematic reviews have demonstrated a survival benefit associated with use of mistletoe injection therapy alongside chemotherapy or as a supportive therapy. There is also a large body of evidence indicating that mistletoe therapy improves quality of life, with improvements in global quality of life as well as symptoms such as fatigue, nausea and vomiting, pain, sleep disturbances, loss of appetite, and constipation found in a preliminary study. Finally, mistletoe therapy appears to reduce side effects of chemotherapy without decreasing its effectiveness.
    [Show full text]
  • Inhibition of Calcium-Independent Phospholipase A2 Induces
    INHIBITION OF CALCIUM-INDEPENDENT PHOSPHOLIPASE A2 INDUCES PROSTATE CANCER CELL CYTOSTASIS by BIN SUN (Under the Direction of Brian S. Cummings) ABSTRACT The goal of this work was to identify mechanisms by which inhibition of calcium- independent phospholipase A2 (iPLA2) induces cytostasis in human LNCaP (p53 wild-type and androgen-sensitive) and PC-3 (p53 negative and androgen-insensitive) prostate cancer cells. Both the iPLA2 selective inhibitor bromoenol lactone (BEL) and iPLA2 siRNA induced cytostasis. Cytostasis correlated to a G1/G0 arrest in LNCaP cells and a G2/M arrest in PC-3 cells. In LNCaP cells, G1 arrest was preceded by increases in tumor suppresser protein p53 and p21. In contrast, neither p53 nor p21 was detectable in PC-3 cells, suggesting that BEL activates p21 independently of p53. Further, the iPLA2 selective inhibitor S-BEL had greater affects on cytostasis, phosphorylated (P)-p53 (Ser15), p53 and p21 expression than the iPLA2 inhibitor R- BEL, suggesting that iPLA2 plays more important roles in cytostasis and p53/p21 epxression than iPLA2. BEL decreased cell growth correlated to activation of p38MAPK in both cells. In contrast, BEL only transiently induced ERK in PC-3 cells but not in LNCaP and did not activate JNK in either cell line. Pharmacological inhibition of p38 inhibited BEL-induced increases in P- p53 (Ser15), p53 and p21 as well as G1 arrest in LNCaP cells. BEL treatment also induced reactive species (RS) in PC-3 and LNCaP cells. The antioxidant NAC inhibited BEL-induced RS, p38, p53 and cytostasis in LNCaP cells and attenuated BEL induced RS and cytostasis in PC-3 cells, supporting the hypothesis that RS mediated cytostasis induced by iPLA2 inhibition.
    [Show full text]
  • Prerequisites for the Antitumor Vaccine-Like Effect Of
    Prerequisites for the Antitumor Vaccine-Like Effect of Chemotherapy and Radiotherapy Dalil Hannani, Antonella Sistigu, Oliver Kepp, Lorenzo Galluzzi, Guido Kroemer, Laurence Zitvogel To cite this version: Dalil Hannani, Antonella Sistigu, Oliver Kepp, Lorenzo Galluzzi, Guido Kroemer, et al.. Prereq- uisites for the Antitumor Vaccine-Like Effect of Chemotherapy and Radiotherapy. Cancer Journal, Lippincott, Williams & Wilkins, 2011, 17, 10.1097/PPO.0b013e3182325d4d. hal-02047421 HAL Id: hal-02047421 https://hal.archives-ouvertes.fr/hal-02047421 Submitted on 17 Dec 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Prerequisites for the Antitumor Vaccine-Like Effect of Chemotherapy and Radiotherapy Dalil Hannani, PhD,* †§ Antonella Sistigu, PhD,* †§ II Oliver Kepp, PhD,*þ§ Lorenzo Galluzzi, PhD,*þ§ Guido Kroemer, MD, PhD,*þ¶L**ÞÞ and Laurence Zitvogel, MD, PhD*Þ§ From the *Institut Gustave Roussy, Villejuif, France; †INSERM, U1015, Villejuif, France; ‡INSERM, U848, Villejuif, France; §Universite´ Paris Sud-XI, Villejuif, France; ||Istituto Superiore di Sanita`, Rome, Italy; ¶Metabolomics Platform, Institut Gustave Roussy, Villejuif, France; LCentre de Recherche des Cordeliers, Paris, France; **Pôle de Biologie, Hooˆpital Europe´en Georges Pompidou, Paris, France; ††Universite´ Paris Descartes, Paris, France. Correspondance: Laurence Zitvogel, MD, PhD, INSERM, U1015, Institut Gustave Roussy, F-94805 Villejuif, Paris, France.
    [Show full text]
  • Elucidating Mechanisms of Innate and Acquired Resistance to Pi3ka Inhibition in Head and Neck Squamous Cell Carcinoma Kara M
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository November 2018 Elucidating mechanisms of innate and acquired resistance to PI3Ka inhibition in head and neck squamous cell carcinoma Kara M. Ruicci The University of Western Ontario Supervisor Nichols, Anthony C. The University of Western Ontario Graduate Program in Pathology A thesis submitted in partial fulfillment of the requirements for the degree in Doctor of Philosophy © Kara M. Ruicci 2018 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Oncology Commons Recommended Citation Ruicci, Kara M., "Elucidating mechanisms of innate and acquired resistance to PI3Ka inhibition in head and neck squamous cell carcinoma" (2018). Electronic Thesis and Dissertation Repository. 5788. https://ir.lib.uwo.ca/etd/5788 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected], [email protected]. Abstract The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signalling pathway is aberrantly activated in most head and neck squamous cell carcinomas (HNSCCs). PI3K signalling drives cellular proliferation, protein synthesis and cell survival. Although numerous targeted agents are available to inhibit PI3K signalling, results have been variable and factors influencing response to PI3K inhibition (e.g. genomic aberrations, pathway interconnectivity, acquired drug resistance) are not well defined. In this thesis, we employ a multifaceted approach to elucidate the molecular underpinnings of biomarkers of response and mediators of resistance to PI3K inhibition in HNSCC.
    [Show full text]
  • 17-Demethoxygeldanamycin (17AAG, NSC 330507), a Novel Inhibitor of Heat Shock Protein 90, in Patients with Refractoryadvanced Cancers Ramesh K
    Cancer Therapy: Clinical Phase I Pharmacokinetic-Pharmacodynamic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (17AAG, NSC 330507), a Novel Inhibitor of Heat Shock Protein 90, in Patients with RefractoryAdvanced Cancers Ramesh K. Ramanathan,1, 3 Donald L.Trump,1, 3 Julie L. Eiseman,1,4 Chandra P. Belani,1, 3 SanjivS. Agarwala, 1, 3 Eleanor G. Zuhowski,1Jing Lan,1 Douglas M. Potter,2 S. Percy Ivy,5 Sakkaraiappan Ramalingam,1, 3 Adam M. Brufsky,1, 3 Michael K.K.Wong,1, 3 SusanTutchko,1and MerrillJ. Egorin1, 3,4 Abstract Purpose: 17-(Allylamino)-17-demethoxygeldanamycin (17AAG), a benzoquinone antibiotic, down-regulates oncoproteins by binding specifically to heat shock protein 90 (HSP90). We did a phase I study of 17AAG to establish the dose-limiting toxicity and maximum tolerated dose and to characterize17AAG pharmacokinetics and pharmacodynamics. Experimental Design: Escalating doses of 17AAG were given i.v. over1or 2 hours on a weekly  3 schedule every 4 weeks to cohorts of three to six patients. Plasma pharmacokinetics of 17AAGand17-(amino)-17-demethoxygeldanamycin (17AG) were assessed by high-performance liquid chromatography. Expression of HSP70 and HSP90 in peripheral blood mononuclear cells was measured byWestern blot. Results: Forty-five patients were enrolled to 11dose levels between 10 and 395 mg/m2.The maximum tolerated dose was 295 mg/m2. Dose-limiting toxicity occurred in both patients (grade 3 pancreatitis and grade 3 fatigue) treated with 395 mg/m2. Common drug-related toxicities (grade1and 2) were fatigue, anorexia, diarrhea, nausea, and vomiting. Reversible elevations ofliver enzymes occurredin 29.5% of patients. Hematologic toxicity was minimal.
    [Show full text]
  • The Changing Pattern of Management for Hormone-Refractory, Metastatic Prostate Cancer
    Prostate Cancer and Prostatic Diseases (2006) 9, 221–229 & 2006 Nature Publishing Group All rights reserved 1365-7852/06 $30.00 www.nature.com/pcan REVIEW The changing pattern of management for hormone-refractory, metastatic prostate cancer ND James1, D Bloomfield2 and C Luscombe3 1Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK; 2Sussex Oncology Centre, Royal Sussex County Hospital, Brighton, UK and 3Department of Urology, University Hospital of North Staffordshire, Stoke-on-Trent, Staffordshire, UK Prostate cancer responds initially to hormonal manipulation by androgen withdrawal and peripheral androgen blockade. The inevitable progression to a hormone-refractory state is accompanied by an exacerbation of local symptoms and metastatic spread, principally to the bones, which has a considerable impact on quality of life and survival. Treatment of hormone- refractory prostate cancer is palliative, and surgery and radiotherapy are used for the relief of lower urinary tract symptoms and localized painful bony metastases. Systemic treatments are not widely accepted in this setting, but clinical trials have demonstrated the potential for bone targeting agents such as strontium-89 and the bisphosphonates to palliate painful bone metastases and to delay progression in certain settings. Chemotherapy with mitozantrone in combination with steroids has previously been shown to have palliative benefits and to delay progression. The additional costs incurred by the use of chemotherapy or bone-targeting therapies may be offset by gains in overall care with fewer in-patient admissions compared with steroid monotherapy . Recent clinical trials have demonstrated that docetaxel significantly improves patient quality of life, and importantly, increases survival. Future studies investigating the timing of chemotherapy, combinations with existing treatments or other novel therapies are underway.
    [Show full text]
  • The Novel Dual PI3K/Mtor Inhibitor GDC-0941 Synergizes with the MEK Inhibitor U0126 in Non-Small Cell Lung Cancer Cells
    MOLECULAR MEDICINE REPORTS 5: 503-508, 2012 The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells ZU-QUAN ZOU1*, LI-NA ZHANG1*, FENG WANG2, JÉRÔME BELLENGER3, YIN-ZHUO SHEN1 and XIAO-HONG ZHANG1 1Medical School, Ningbo University; 2Clinical Laboratory, Lihuili Hospital, Ningbo 315211, P.R. China; 3UMR 866 Physiopathologie des Dyslipidémies, Faculté des Sciences Gabriel, Université de Bourgogne, Dijon, France Received May 25, 2011; Accepted August 22, 2011 DOI: 10.3892/mmr.2011.682 Abstract. Lung cancer is a malignant disease with poor outcome, witnessed targeted therapy in NSCLC. However, gefitinib, a which has led to a search for new therapeutics. The PI3K/Akt/ specific inhibitor of epidermal growth factor receptor (EGFR) mTOR and Ras/raf/Erk pathways are key regulators of tumor tyrosine kinase, has shown efficacy only in a subgroup of growth and survival. In the present study, their roles were NSCLC patients with EGFR mutations and overexpression. It evaluated by MTT assay, flow cytometry and Western blotting was previously shown that EGFR-independent activation of the in lung cancer cells. We found that a high efficacy of antitumor PI3K/Akt/mammalian target of rapamycin (mTOR) and Ras/ activity was shown with GDC-0941 treatment in two gefitinib- raf/Erk pathways may contribute to the unfavorable treatment resistant non-small cell lung cancer (NSCLC) cell lines, A549 outcome of gefitinib (2). and H460. In addition, H460 cells with activating mutations The PI3K/Akt/mTOR and Ras/raf/Erk signaling pathways of PIK3CA were relatively more sensitive to GDC-0941 than play a key role in cell growth, proliferation and survival in a A549 cells with wild-type PIK3CA.
    [Show full text]
  • Phase I Pharmacokinetic and Pharmacodynamic Study of 17
    VOLUME 23 ⅐ NUMBER 18 ⅐ JUNE 20 2005 JOURNAL OF CLINICAL ONCOLOGY ORIGINAL REPORT Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino, 17-Demethoxygeldanamycin in Patients With Advanced Malignancies Udai Banerji, Anne O’Donnell, Michelle Scurr, Simon Pacey, Sarah Stapleton, Yasmin Asad, Laura Simmons, Alison Maloney, Florence Raynaud, Maeli Campbell, Michael Walton, Sunil Lakhani, Stanley Kaye, Paul Workman, and Ian Judson From the Cancer Research UK Centre for Cancer Therapeutics, The Institute ABSTRACT of Cancer Research; Section of Medi- cine, The Institute of Cancer Research; Purpose The Royal Marsden Hospital, Sutton; To study the toxicity and pharmacokinetic-pharmacodynamic profile of 17-allylamino, 17- Cancer Research UK, Drug Development demethoxygeldanamycin (17-AAG) and to recommend a dose for phase II trials. Office; and Breakthrough Breast Cancer Research Centre, Institute of Cancer Patients and Methods Research, London, United Kingdom. This was a phase I study examining a once-weekly dosing schedule of 17-AAG. Thirty patients with advanced malignancies were treated. Submitted November 30, 2004; accepted January 18, 2005. Results 2 Supported by Cancer Research UK. The highest dose level reached was 450 mg/m /week. The dose-limiting toxicities (DLTs) encountered were grade 3 diarrhea in three patients (one at 320 mg/m2/week and two at 450 Presented in part at the 37th Annual 2 2 Meeting of the American Society of mg/m /week) and grade 3 to 4 hepatotoxicity (AST/ALT) in one patient at 450 mg/m /week. Clinical Oncology, San Francisco, CA, Two of nine DLTs were at the highest dose level. Two patients with metastatic melanoma May 12-15, 2001; 39th Annual Meeting had stable disease and were treated for 15 and 41 months, respectively.
    [Show full text]