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12. p53 protein expression in squamous cell carcinoma of the vulva

Author

Scheistroen, Marit, Trope, Claes, Pettersen, Erik O., and Nesland, Jahn M.

Subjects
Squamous cell carcinoma -- Prognosis, Vulvar cancer -- Prognosis, Tumor suppressor genes -- Health aspects, Gene expression -- Health aspects, Health
Published
1999

14. Malignant melanoma of the vulva: evaluation of prognostic factors with emphasis on DNA ploidy in 75 patients

Author

Scheistroen, Marit, Trope, Claes, Kaern, Janne, Pettersen, Erik O., Abeler, Vera M., and Kristensen, Gunnar B.

Subjects
Vulvar cancer -- Prognosis, Melanoma -- Prognosis, Ploidy -- Usage, Health
Abstract

Background. To the authors' knowledge, the potential prognostic value of DNA ploidy in vulvar melanoma has not been evaluated in previous series. Methods. Clinical data and follow-up information were retrieved from the hospital records of 75 patients treated from 1956 to 1987. Histopathologic specimens were reviewed for histologic type, depth of invasion, vessel invasion, and ulceration. Flow cytometric DNA measurements were performed on paraffin embedded samples. Results. Forty-three patients had International Federation of Gynecology and Obstetrics Stage I disease, 14 Stage II, 8 Stage III and 10 Stage IV. Sixty-five patients were treated by surgery, six by radiotherapy, and four patients with advanced disease received no therapy. The surgical procedure was local excision in 17 patients, vulvectomy in 22, and radical vulvectomy with inguinal lymph node dissection in 26. Five- and 10-year corrected survival rates were 46% and 37%, respectively. Recurrences were seen in 43 (66%) of the patients treated by surgery. Independent prognostic factors for corrected survival in the entire group of 75 patients were inguinal lymph node metastases (P = 0.016), angioinvasion (P = 0.027), tumor localization to clitoris, and multifocal tumors (P = 0.043). For the 65 patients treated by surgery, independent prognostic factors for disease free survival were angioinvasion (P < 0.001), age at diagnosis (P = 0.003), DNA ploidy (P = 0.004), and ulceration (P = 0.027). The independent prognostic factors for long term survival were tumor localization to clitoris.(P = 0.018), DNA ploidy (P = 0.045), and inguinal lymph node involvement (P = 0.053). Radical surgery did not improve disease free or long term survival. Conclusions. DNA ploidy is an independent factor that predicts prognosis in patients with vulvar melanoma, and should be considered together with previously known factors. Radical surgery does not improve prognosis and is not recommended when the inguinal lymph nodes are clinically negative.

Published
1995

16. Flow cytometric DNA ploidy and S-phase heterogeneity in advanced ovarian carcinoma

Author

Koern, Janne, Trope, Claes G., Kristensen, Gunnar B., and Pettersen, Erik O.

Subjects
Flow cytometry -- Diagnostic use, Ploidy, Ovarian cancer -- Genetic aspects, Health
Abstract

Background. The prognostic significance of flow cytometric DNA ploidy and S-phase fraction (SPF) in ovarian cancer has been controversial. In the current study, the authors analyzed tumor heterogeneity in respect to DNA index DI and SPF. Methods. Flow cytometric variation in DI and SPF among representative fresh tumor material from the primary tumor, metastasis, and malignant effusions from the same patient was analyzed. Results. One hundred thirty-two samples from 47 patients were analyzed, and 119 samples from 42 patients were evaluable. Stable DI between different samples was found in 34 patients, whereas heterogeneity was found in 8 patients (19%). The metastases showed stable DNA content. The malignant effusion samples often lacked tumor cells. The representative ones were often DNA diploid. In 21% of the aneuploid samples, the SPF could not be analyzed. In 38% of the aneuploid samples, the stem line constituted less than 15% of measured nuclei. In these samples, a negative correlation between SPF and percentage of aneuploid cells was found, making SPF unreliable. Correct SPF measurement was thus possible in only 41% of the aneuploid samples, and in these tumors, SPF values varied considerably among different samples from the same patient, illustrated by a median SPF difference of 11% (range, 0-28%). Conclusions. Tumor DI heterogeneity existed in 19% of tumors. SPF depended on the amount of aneuploid cells in case of small stem lines and varied considerably, making its use as a prognostic factor doubtful. To ensure that all tumor stem lines are represented, at least two biopsy specimens from any solid tumor should be analyzed. Cancer 1994; 73:1870-7. Key words: ovarian carcinoma, tumor heterogeneity, DNA ploidy, S-phase fraction.

Published
1994

17. Aneuploidy in benign tumors and nonneoplastic lesions of musculoskeletal tissues

Author

Alho, Antti, Skjeldal, Sigmund, Pettersen, Erik O., Melvik, Jan E., and Larsen, Tove E.

Subjects
Aneuploidy -- Research, Muscle diseases -- Genetic aspects, Cancer -- Genetic aspects, Flow cytometry -- Diagnostic use, Health
Abstract

Background. Aneuploidy in DNA flow cytometry (FCM) of musculoskeletal tumors is generally considered to be a sign of malignancy. Previously, giant cell tumor of the bone has been reported to contain aneuploid (near0diploid) DNA stemlines. Otherwise, only sporadic cases have been reported. The authors wanted to study the relationships among DNA FCM, histology, and clinical course of nonmalignant musculoskeletal lesions. Methods. Twenty-eight histologically benign tumors and seven nonnepolastic lesions were subjected to DNA FCM. After tissue preparation mechanically and with ribonuclease and trypsin, the isolated nuclei were stained with propidium iodine using chicken and rainbow trout erythrocytes as controls. In the DNA FCM histograms, ploidy and cell cycle fractions were determined using a computerized mathematical model. The histologic diagnoses were made without knowledge of the DNA FCM results. Results. Aneuploidy was found in eight lesions. A shoulder in the diploid peak, suggesting a diploid and a near-diploid population, was found in DNA histograms of a condensing osteitis of the clavicle (a benign inflammatory process) and of a giant cell tumor of bone. The latter lesion also had a tetraploid population. Six benign tumors--two enchondromas, one osteochondroma, one subcutaneous and one intramuscular lipoma, and a calcifying aponeurotic fibroma--showed clear aneuploidy with separate peaks. The S-phase fraction was less than 10% in all cases. The highest aneuploid population, DNA index = 1.70, in a subcutaneous lipoma, was small, with an undetectable S phase. Despite nonradical operations in seven lesions, no recurrences were observed during a median follow-up of 49 months (range, 28--73 months). Conclusions. Small aneuploid populations with low DNA synthetic activity may be compatible with a benign histologic picture and uneventful clinical course of the musculoskeletal lesion. Cancer 1994; 73:1200--5.

Published
1994

19. Rheological characterization of an injectable alginate gel system

Author

Larsen, Benjamin E, Bjørnstad, Jorunn, Pettersen, Erik O, Tønnesen, Hanne H, and Melvik, Jan E

Abstract

Background This work investigates a general method for producing alginate gel matrices using an internal mode of gelation that depends solely on soluble alginate and alginate/gelling ion particles. The method involves the formulation of two-component kits comprised of soluble alginate and insoluble alginate/gelling ion particles. Gelling kinetics, elastic and Young’s moduli were investigated for selected parameters with regard to soluble alginate guluronate content, molecular weight, calcium or strontium gelling ions and alginate gelling ion particle sizes in the range between 25 and 125 micrometers. Results By mixing the two components and varying the parameters mentioned above, alginate gel matrices with tailor-made viscoelastic properties and gelling kinetics were obtained. Final gel elasticity depended on alginate type, concentration and gelling ion. The gelling rate could be manipulated, e.g. through selection of the alginate type and molecular weight, particle sizes and the concentration of non-gelling ions. Conclusions Formulations of the injectable and moldable alginate system presented have recently been used within specific medical applications and may have potential within regenerative medicine or other fields.

Published
2015

20. Preface

Author

Giacomello, Alessandro, Peters, G. J., Eriksson, Staffan, De Abreu, Ronney, Kristensen, T., Munch-Petersen, B., Vincenzetti, S., Cambi, A., Neuhard, J., Garattini, E., Vita, A., Oka, J., Matsumoto, A., Hosokawa, Y., Inoue, S., Allegrini, S., Johnson, R. B., Fiol, C. J., Eriksson, S., Fabianowska-Majewska, K., Wasiak, T., Duley, J., Simmonds, A., Bretner, M., Felczak, K., Poznański, J., Dzik, J. M., Golos, B., Jarmuła, A., Rode, W., Kulikowski, T., Codacci-Pisanelli, G., Pinedo, H. M., Noordhuis, P., van Groeningen, C. J., van der Wilt, C. L., Franchi, F., Hatse, S., Balzarini, J., De Clercq, E., Marinello, E., Rosi, F., Dispensa, E., Mangiavacchi, P., Riario-Sforza, G., Agostinho, A. B., Smolenski, R. T., Müller, Mathias M., Roch-Ramel, F., Guisan, B., Diezi, J., Tavenier, M., Skladanowski, A. C., de Abreu, R. A., de Jong, J. W., Åmellem, Øystein, Löffler, Monika, Pettersen, Erik O., Boulieu, R., Lenoir, A., Bertocchi, M., Mornex, J. F., Makarewicz, W., Spychala J., Mitchell B. S., Barankiewcz J., Góra-Tybor, Joanna, Robak, Tadeusz, Spasokukotskaja T., Sasvári-Székely M., Piróth Zs., Kazimierczuk Z., Staub M., Keuzenkamp-Jansen, C W, De Abreu, R A, Bökkerink, J P M, Trijbels, J M F, Eriksson S., Warzocha, K., Krykowski, E., Góra-Tybor, J., Fronczak, A., Robak, T., Minelli, A., Moroni, M., Monacelli, N., Mezzasoma, I., Amici, A., Emanuelli, M., Raffaelli, N., Ruggieri, S., Magni, G., Carta, M. C., Mattana, A., Poddie, F., Sgarrella, F., Tozzi, M. G., Veerman, G., Ruiz van Haperen, V. W. T., van Moorsel, C. J. A., Pesi, R., Baiocchi, C., Camici, M., Ipata, P. L., Kozłowska, M., Świerczyński, J., Smoleński, R. T., Jastorff, B., Messina, E., Savini, F., Procopio, A., Giacomello, A., Wielgus-Kutrowska, B., Kulikowska, E., Wierzchowski, J., Bzowska, A., Shugar, D., Fairbanks, Lynette D, Ruckemann, Katarzyna, Simmonds, H Anne, Kaletha, K., Szymańska, G., Thebault, M., Raffin, J. P., Le Gal, Y., Griesmacher, Andrea, De Abreu, Ronney A., Zych, M., Ruckemann, K., Jagodzinski, P., Kochan, Z., Stolk, J., Boerbooms, A., De Abreu, R., de Koning, D., van de Putte, L., Fiorini, M., Bazzichi, L., Bertolini, G., Martini, C., Ciompi, M. L., Lucacchini, A., Pizzichini, M., Terzuoli, L., Arezzini, L., Fe, L., Pagani, R., Miscetti, P., Allegrucci, C., Sebesta, I., Duley, J. A., Simmonds, H. A., Gross, M., Salerno, C., Stone, T. W., Van den Berghe, G., Valik, Dalibor, Jones, James D., Guerranti, R., Fè, L., Sforza, G. Riario, Knecht, Wolfgang, Grein, Klaus, Lodi, R., Iotti, S., Barbiroli, B., Bonin, B., Chantin, C., Bory, C., Micheli, V., Jacomelli, G., Morozzi, G., Fioravanti, A., Marcolongo, R., Pompucci, G., Peters G J, Noordhuis P, Komissarov A, Holwerda U, Kok R M, Van Laar J A M, Van der Wilt C L, Van Groeningen C J, Pinedo H M, Perrett, David, Jacobsson, Bengt, Sisto A., Iezzi A., Di Carlo M., Pizzigallo E., Akhondzadeh, S., MacGregor, D. G., Ogilvy, H. V., Zoref-Shani, E., Brosh, S., Sidi, Y., Bromberg, Y., Sperling, O., van Gennip, A. H., Abeling, N. G. G. M., Stroomer, A. E. M., van Lenthe, H., Bakker, H. D., van Kuilenburg, A. B. P., Connolly, G. P., Abbott, N. J., Lilling, G., Gozes, I., Vreken, P., Meinsma, R., de Ahreu, R. A., Diasio, R. B., Albin, N., Johnson, M. R., Shahinian, H., Wang, K., Gathof, B. S., Rocchigiani, M., Puig, J. G., Mateos, F., Sestini, S., Krijt, J., Shin, Y., Gresser, U., Costa, A., Maximova, N., Andolina, M., Paci, M., Carrozzi, M., Osbich, A., Durighello, M., Cavalli, F., Geatti, O., Zammarchi, E., Morgan, Gareth, Webster, A. D. B., Slavin, S., Naparstek, E., Nagler, A., Acker, M., Cividalli, G., Kapellushnik, Y., Varadi, G., Ben-Yoseph, R., Or, R., Parfenov, V. V., Ignatenko, M. A., Amchenkova, A. M., Narovlyansky, A. N., Spoto, G., Mastropasqua, L., Gizzi, F., Arduini, A., Del Gallo, P., Ciancaglini, M., Gallenga, P. E., Šebesta, I., Zeman, J., Crifò, C., Di Vito, M., Lomonte, A., Gerber, G., Carlucci, F., Tabucchi, A., Vannoni P., Di Pietro M. C., Vincent, M. F., Bontemps, F., Boer, P., Rötzer, E., Ehrmann, D., Empl, W., Bride, M. B. Mc, Ogg, C. S., Cameron, J. S., Moro, F., Rigden, S., Rees, L., Hoff, W. Van't, Raman, V., Palmieri, P., Mastropierro, G., Albertazzi, A., Rucci, C., Darlington, L. G., Cotton, S. R., de Gorter, J. J., Lawrence, E. S., Petrie, A., Sarsam, R. P., Semple, M. J., Warburton, E. A., Quaratino, C. P., Talone, L., Di Sciascio, N., Hrebíček, M. H., Poupětová, H., Ledvinová, J., Elleder, M., Vondrák, K., Rees, P. C., Wonke, B., Thein, S. L., Clegg, J. B., Marlewski, M., Pennelli, A., Di Marzio, M., Angelini, G., Sabatino, G., de Koning, P., Kerstens, P., de Graaf, R., Hayek, G., and Cardona, F.

Published
1995
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24. Targeting tumour hypoxia to prevent cancer metastasis. From biology, biosensing and technology to drug development: the METOXIA consortium

Author

Pettersen, Erik O., primary, Ebbesen, Peter, additional, Gieling, Roben G., additional, Williams, Kaye J., additional, Dubois, Ludwig, additional, Lambin, Philippe, additional, Ward, Carol, additional, Meehan, James, additional, Kunkler, Ian H., additional, Langdon, Simon P., additional, Ree, Anne H., additional, Flatmark, Kjersti, additional, Lyng, Heidi, additional, Calzada, Maria J., additional, Peso, Luis del, additional, Landazuri, Manuel O., additional, Görlach, Agnes, additional, Flamm, Hubert, additional, Kieninger, Jochen, additional, Urban, Gerald, additional, Weltin, Andreas, additional, Singleton, Dean C., additional, Haider, Syed, additional, Buffa, Francesca M., additional, Harris, Adrian L., additional, Scozzafava, Andrea, additional, Supuran, Claudiu T., additional, Moser, Isabella, additional, Jobst, Gerhard, additional, Busk, Morten, additional, Toustrup, Kasper, additional, Overgaard, Jens, additional, Alsner, Jan, additional, Pouyssegur, Jacques, additional, Chiche, Johanna, additional, Mazure, Nathalie, additional, Marchiq, Ibtissam, additional, Parks, Scott, additional, Ahmed, Afshan, additional, Ashcroft, Margaret, additional, Pastorekova, Silvia, additional, Cao, Yihai, additional, Rouschop, Kasper M., additional, Wouters, Brad G., additional, Koritzinsky, Marianne, additional, Mujcic, Hilda, additional, and Cojocari, Dan, additional

Published
2014
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27. Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies

Author

Ebbesen, Peter, primary, Pettersen, Erik O., additional, Gorr, Thomas A., additional, Jobst, Gerhard, additional, Williams, Kaye, additional, Kieninger, Jochen, additional, Wenger, Roland H., additional, Pastorekova, Silvia, additional, Dubois, Ludwig, additional, Lambin, Philippe, additional, Wouters, Brad G., additional, Van Den Beucken, Twan, additional, Supuran, Claudiu T., additional, Poellinger, Lorenz, additional, Ratcliffe, Peter, additional, Kanopka, Arvydas, additional, Görlach, Agnes, additional, Gasmann, Max, additional, Harris, Adrian L., additional, Maxwell, Patrick, additional, and Scozzafava, Andrea, additional

Published
2009
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30. Targeting tumour hypoxia to prevent cancer metastasis. From biology, biosensing and technology to drug development: the METOXIA consortium.

Author

Pettersen, Erik O., Ebbesen, Peter, Gieling, Roben G., Williams, Kaye J., Dubois, Ludwig, Lambin, Philippe, Ward, Carol, Meehan, James, Kunkler, Ian H., Langdon, Simon P., Ree, Anne H., Flatmark, Kjersti, Lyng, Heidi, Calzada, Maria J., Peso, Luis del, Landazuri, Manuel O., Görlach, Agnes, Flamm, Hubert, Kieninger, Jochen, and Urban, Gerald

Subjects
*METASTASIS, *DRUG development, *TARGETED drug delivery, *BIOSENSORS, *ANTINEOPLASTIC agents, *PROGNOSIS, *PREVENTION
Abstract

The hypoxic areas of solid cancers represent a negative prognostic factor irrespective of which treatment modality is chosen for the patient. Still, after almost 80 years of focus on the problems created by hypoxia in solid tumours, we still largely lack methods to deal efficiently with these treatment-resistant cells. The consequences of this lack may be serious for many patients: Not only is there a negative correlation between the hypoxic fraction in tumours and the outcome of radiotherapy as well as many types of chemotherapy, a correlation has been shown between the hypoxic fraction in tumours and cancer metastasis. Thus, on a fundamental basis the great variety of problems related to hypoxia in cancer treatment has to do with the broad range of functions oxygen (and lack of oxygen) have in cells and tissues. Therefore, activation–deactivation of oxygen-regulated cascades related to metabolism or external signalling are important areas for the identification of mechanisms as potential targets for hypoxia-specific treatment. Also the chemistry related to reactive oxygen radicals (ROS) and the biological handling of ROS are part of the problem complex. The problem is further complicated by the great variety in oxygen concentrations found in tissues. For tumour hypoxia to be used as a marker for individualisation of treatment there is a need for non-invasive methods to measure oxygen routinely in patient tumours. A large-scale collaborative EU-financed project 2009–2014 denoted METOXIA has studied all the mentioned aspects of hypoxia with the aim of selecting potential targets for new hypoxia-specific therapy and develop the first stage of tests for this therapy. A new non-invasive PET-imaging method based on the 2-nitroimidazole [18F]-HX4 was found to be promising in a clinical trial on NSCLC patients. New preclinical models for testing of the metastatic potential of cells were developed, bothin vitro(2D as well as 3D models) and in mice (orthotopic grafting). Low density quantitative real-time polymerase chain reaction (qPCR)-based assays were developed measuring multiple hypoxia-responsive markers in parallel to identify tumour hypoxia-related patterns of gene expression. As possible targets for new therapy two main regulatory cascades were prioritised: The hypoxia-inducible-factor (HIF)-regulated cascades operating at moderate to weak hypoxia (<1% O2), and the unfolded protein response (UPR) activated by endoplasmatic reticulum (ER) stress and operating at more severe hypoxia (<0.2%). The prioritised targets were the HIF-regulated proteins carbonic anhydrase IX (CAIX), the lactate transporter MCT4 and the PERK/eIF2α/ATF4-arm of the UPR. The METOXIA project has developed patented compounds targeting CAIX with a preclinical documented effect. Since hypoxia-specific treatments alone are not curative they will have to be combined with traditional anti-cancer therapy to eradicate the aerobic cancer cell population as well. [ABSTRACT FROM AUTHOR]

Published
2015
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