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4. Ex Vivo Vascular Imaging and Perfusion Studies of Normal Kidney and Tumor Vasculature.

Author

Hultborn, Ragnar, Weiss, Lilian, Tveit, Egil, Lange, Stefan, Jennische, Eva, Erlandsson, Malin C., and Johansson, Martin E.

Subjects
*RESEARCH funding, *BARIUM sulfate, *IMMUNOHISTOCHEMISTRY, *RENAL cell carcinoma, *PERFUSION, *TUMORS, *MICROSCOPY, *VASCULAR diseases, *KIDNEYS
Abstract

Simple Summary: Organs as well as cancer require a supply of nutrients and oxygen and removal of waste products. These tasks are carried out by the vascular system. Knowledge of the vascular properties in organs and tumors is key for understanding normal and abnormal function. For cancer, vascular function is also highly relevant to understand response to treatment, metastasis, and tumor progression. In this study, we use various techniques to characterize the vascular tree and flow in kidneys with kidney cancer. We connected kidneys to a perfusion system and used barium sulphate contrast to visualize the vascular architecture contact microangiography. Immunohistochemistry was used to visualize the vessels in relation to perfusion. The vascular resistance was measured using the radioactive microspheres and in cases that were feasible, we used micro-CT to characterize the vascular tree. This work aims to suggest the use of these techniques for any organ or tumor available for ex vivo perfusion. This work describes a comprehensive study of the vascular tree and perfusion characteristics of normal kidney and renal cell carcinoma. Methods: Nephrectomy specimens were perfused ex-vivo, and the regional blood flow was determined by infusion of radioactive microspheres. The vascular architecture was characterized by micronized barium sulphate infusion. Kidneys were subsequently sagitally sectioned, and autoradiograms were obtained to show the perfusate flow in relation to adjacent contact X-ray angiograms. Vascular resistance in defined tissue compartments was quantified, and finally, the tumor vasculature was 3D reconstructed via the micro-CT technique. Results show that the vascular tree of the kidney could be distinctly defined, and autoradiograms disclosed a high cortical flow. The peripheral resistance unit of the whole perfused specimen was 0.78 ± 0.40 (n = 26), while that of the renal cortex was 0.17 ± 0.07 (n = 15 with 114 samples). Micro-CT images from both cortex and medulla defined the vascular architecture. Angiograms from the renal tumors demonstrated a significant vascular heterogeneity within and between different tumors. A dense and irregular capillary network characterized peripheral tumor areas, whereas central parts of the tumors were less vascularized. Despite the dense capillarity, low perfusion through vessels with a diameter below 15 µm was seen on the autoradiograms. We conclude that micronized barium sulphate infusion may be used to demonstrate the vascular architecture in a complex organ. The vascular resistance was low, with little variation in the cortex of the normal kidney. Tumor tissue showed a considerable vascular structural heterogeneity with low perfusion through the peripheral nutritive capillaries and very poor perfusion of the central tumor, indicating intratumoral pressure exceeding the perfusion pressure. The merits and shortcomings of the various techniques used are discussed. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Swedish Public Health Agency reporting has distorted mortality rates for the unvaccinated and the vaccinated

Author

Littorin, Nils, Stahel, Anette, Engwall, Ann-Cathrin, Hultborn, Ragnar, Blomberg, Sture, Weiss, Lilian, Lundström, Niklas, Klanger, Boris, Dusceac, Dinu, Hartmann-Petersen, Susanna, Jonsson, Bo, Wiedemann, Anna Maria, Nilson, Roger, Liljedahl, Anne, Hellmundt, Ludwig, Yderberg, Nina, Åsberg, Hanna, Pilgram, Constanze, Ljungfelt, Carina, Krüger, Ute, Olsson Vallander, Karin, Höglund, Ida, Palmlöf, Lisa, Slotte, Delia, Andersson, Margareta, Burling, Magnus, Mattson, Sara, Kaminer, Arnaldo, Wadenbäck, Johan, Littorin, Nils, Stahel, Anette, Engwall, Ann-Cathrin, Hultborn, Ragnar, Blomberg, Sture, Weiss, Lilian, Lundström, Niklas, Klanger, Boris, Dusceac, Dinu, Hartmann-Petersen, Susanna, Jonsson, Bo, Wiedemann, Anna Maria, Nilson, Roger, Liljedahl, Anne, Hellmundt, Ludwig, Yderberg, Nina, Åsberg, Hanna, Pilgram, Constanze, Ljungfelt, Carina, Krüger, Ute, Olsson Vallander, Karin, Höglund, Ida, Palmlöf, Lisa, Slotte, Delia, Andersson, Margareta, Burling, Magnus, Mattson, Sara, Kaminer, Arnaldo, and Wadenbäck, Johan

Published
2022

19. Intraperitoneal Alpha-emitting Radio Immunotherapy with Astatine-211 in Relapsed Ovarian Cancer; Long-term Follow-up with Individual Absorbed Dose Estimations

Author

Hallqvist, Andreas, primary, Albertsson, Per, additional, Hultborn, Ragnar, additional, Palm, Stig, additional, Bergmark, Karin, additional, Bäck, Tom, additional, Andersson, Håkan, additional, Dahm-Kähler, Pernilla, additional, Johansson, Mia, additional, Lindegren, Sture, additional, Jensen, Holger, additional, and Jacobsson, Lars, additional

Published
2019
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21. Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations

Author

Hallqvist, Andreas, primary, Bergmark, Karin, additional, Bäck, Tom, additional, Andersson, Håkan, additional, Dahm-Kähler, Pernilla, additional, Johansson, Mia, additional, Lindegren, Sture, additional, Jensen, Holger, additional, Jacobsson, Lars, additional, Hultborn, Ragnar, additional, Palm, Stig, additional, and Albertsson, Per, additional

Published
2019
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30. Absorbed Doses and Risk Estimates of 211At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients

Author

Cederkrantz, Elin, primary, Andersson, Håkan, additional, Bernhardt, Peter, additional, Bäck, Tom, additional, Hultborn, Ragnar, additional, Jacobsson, Lars, additional, Jensen, Holger, additional, Lindegren, Sture, additional, Ljungberg, Michael, additional, Magnander, Tobias, additional, Palm, Stig, additional, and Albertsson, Per, additional

Published
2015
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31. Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200

Author

Lindegren, Sture, primary, Andrade, Luciana N. S., additional, Bäck, Tom, additional, Machado, Camila Maria L., additional, Horta, Bruno Brasil, additional, Buchpiguel, Carlos, additional, Moro, Ana Maria, additional, Okamoto, Oswaldo Keith, additional, Jacobsson, Lars, additional, Cederkrantz, Elin, additional, Washiyama, Kohshin, additional, Aneheim, Emma, additional, Palm, Stig, additional, Jensen, Holger, additional, Tuma, Maria Carolina B., additional, Chammas, Roger, additional, Hultborn, Ragnar, additional, and Albertsson, Per, additional

Published
2015
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33. Therapeutic efficacy of α-radioimmunotherapy with different activity levels of the Bi-labeled monoclonal antibody MX35 in an ovarian cancer model.

Author

Gustafsson-Lutz, Anna, Bäck, Tom, Aneheim, Emma, Hultborn, Ragnar, Palm, Stig, Jacobsson, Lars, Morgenstern, Alfred, Bruchertseifer, Frank, Albertsson, Per, and Lindegren, Sture

Subjects
DRUG efficacy, THERAPEUTIC use of monoclonal antibodies, OVARIAN cancer treatment, CANCER cells, INTRAPERITONEAL injections, CANCER treatment
Abstract

Background: The aim of this study was to compare the therapeutic efficacy of two different activity levels of the Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of Bi-MX35, 3 MBq/mL ( n = 20), or 9 MBq/mL ( n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy. Body weight and white blood cell counts were monitored after treatment for possible signs of toxicity. Results: The tumor-free fraction of the animals treated with 3 MBq/mL of Bi-MX35 was 0.55, whereas that of animals treated with 9 MBq/mL of Bi-MX35 was 0.78. The control group treated with unlabeled MX35 had a tumor-free fraction of 0.15. No significant reduction in white blood cell counts or weight loss was observed. Conclusions: Tumor growth after i.p. treatment with Bi-MX35 was significantly reduced compared to treatment with unlabeled MX35. Treatment with 9 MBq/mL of Bi-MX35 resulted in higher tumor-free fraction compared with 3 MBq/mL of Bi-MX35, but this difference was not statistically significant. No signs of toxicity were observed in the treated animals. [ABSTRACT FROM AUTHOR]

Published
2017
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36. Irradiation of myxoid/round cell liposarcoma induces volume reduction and lipoma-like morphology

Author

Engström, Katarina, Bergh, Peter, Cederlund, Claes-Göran, Hultborn, Ragnar, Willen, Helena, Aman, Pierre, Kindblom, Lars-Gunnar, Meis-Kindblom, Jeanne M., Engström, Katarina, Bergh, Peter, Cederlund, Claes-Göran, Hultborn, Ragnar, Willen, Helena, Aman, Pierre, Kindblom, Lars-Gunnar, and Meis-Kindblom, Jeanne M.

Abstract

The aim of the study was to investigate the clinical and morphological effects of radiotherapy in the treatment of myxoid/round cell liposarcoma (MLS/RCLS). Thirty-three primary and metastatic MLS/RCLS tumours in 15 patients were treated with radiation therapy. Twenty-seven of the 33 tumours were surgically removed after preoperative radiation (34-46 Gy) while six tumours were treated with radiotherapy alone (44-60 Gy). The pretreatment diagnosis was established in all 15 patients based on fine needle aspirates or histological findings. Tumour size was measured by CT or MRI before and after radiotherapy in 30 tumours. Thirteen tumours from 11 patients were genetically characterised before and/or after radiation therapy. Twenty-three of 30 irradiated tumours showed a median reduction in tumour volume of 52% and seven lesions a median progression of 36%. All 27 surgically removed tumours revealed histological features of radiation response. The most striking morphological changes were lipoma-like appearance, paucicellularity and hyalinisation. Twelve of 13 tumours analysed before and/or after radiation therapy showed the FUS-DDIT3 translocation. Radiation therapy of MLS/RCLS induces histopathologic accumulation of mature lipoma-like areas and tumour volume reduction that may facilitate resectability.

Published
2007
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37. TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer

Author

Villman, Kenneth, Sjöström, Johanna, Heikkilä, Reino, Hultborn, Ragnar, Malmström, Per, Bengtsson, Nils-Olof, Söderberg, Martin, Saksela, Eero, Blomqvist, Carl, Villman, Kenneth, Sjöström, Johanna, Heikkilä, Reino, Hultborn, Ragnar, Malmström, Per, Bengtsson, Nils-Olof, Söderberg, Martin, Saksela, Eero, and Blomqvist, Carl

Abstract

The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer. Gene copy number of TOP2A and HER2 were analysed with chromogenic in situ hybridization (CISH) on paraffin-embedded tissue sections from the primary tumour of 85 patients treated with anthracycline containing chemotherapy. TOP2A gene amplification was present in 14 (16%) and HER2 gene amplification in 38 (45%) of the primary tumours. Two of the 14 cases with TOP2A amplification were amplified without concurrent HER2 amplification. Neither TOP2A nor HER2 gene amplification were significantly associated with response to chemotherapy (p = 0.35 and p = 0.49, respectively).

Published
2006
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47. Physical performance, toxicity, and quality of life as assessed by the physician and the patient

Author

Luoma, Minna-Liisa, Hakamies-Blomqvist, Liisa, Sjöström, Johanna, Mouridsen, Henning, Pluzanska, Anna, Malmström, Per, Bengtsson, Nils Olof, Hultborn, Ragnar, Ostenstaad, Björn, Mjaaland, Ingvil, Valvere, Vahur, Wist, Erik, Baldursson, Gudjon, Ahlgren, Johan, Blomqvist, Carl, Luoma, Minna-Liisa, Hakamies-Blomqvist, Liisa, Sjöström, Johanna, Mouridsen, Henning, Pluzanska, Anna, Malmström, Per, Bengtsson, Nils Olof, Hultborn, Ragnar, Ostenstaad, Björn, Mjaaland, Ingvil, Valvere, Vahur, Wist, Erik, Baldursson, Gudjon, Ahlgren, Johan, and Blomqvist, Carl

Abstract

The aim of this study was to study the relationship between physician-assessed quality of life parameters, i.e., toxicity and physical performance, and patients' self-reports of their quality of life (QoL). QoL was assessed at baseline and before each treatment, using the EORTC QLQ-C30. The WHO performance score (PS) and toxicity were assessed in physician interviews. The correlations between the WHO PS and the QLQ-C30 functioning scale scores varied from weak to moderate, depending on the scale. Strongest associations were found in physical-, social-, and role functioning, and in the global QoL. The QLQ-C30 nausea/vomiting and diarrhea scales correlated moderately to corresponding WHO scores. A multiple linear regression analysis was used to analyze the contribution of WHO PS and toxicity variables to the global QoL. The best model explained only 16% of the variance of the global QoL score. The present findings highlight the importance of independent QoL assessments focused on those aspects of QoL not captured in clinical interviews with the physician.

Published
2002

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