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12 results on '"Selander, K S"'

1. CD73 regulates zoledronate-induced lymphocyte infiltration in triple-negative breast cancer tumors and lung metastases

Author

Petruk, N. (Nataliia), Siddiqui, A. (Arafat), Tadayon, S. (Sina), Määttä, J. (Jorma), Mattila, P. K. (Pieta K.), Jukkola, A. (Arja), Sandholm, J. (Jouko), Selander, K. S. (Katri S.), Petruk, N. (Nataliia), Siddiqui, A. (Arafat), Tadayon, S. (Sina), Määttä, J. (Jorma), Mattila, P. K. (Pieta K.), Jukkola, A. (Arja), Sandholm, J. (Jouko), and Selander, K. S. (Katri S.)

Abstract

Introduction: Bisphosphonates (BPs) are bone-protecting osteoclast inhibitors, typically used in the treatment of osteoporosis and skeletal complications of malignancies. When given in the adjuvant setting, these drugs may also prevent relapses and prolong overall survival in early breast cancer (EBC), specifically among postmenopausal patients. Because of these findings, adjuvant nitrogen-containing BPs (N-BPs), such as zoledronate (ZOL), are now the standard of care for high-risk EBC patients, but there are no benefit-associated biomarkers, and the efficacy remains low. BPs have been demonstrated to possess anti-tumor activities, but the mechanisms by which they provide the beneficial effects in EBC are not known. Methods: We used stably transfected 4T1 breast cancer cells together with suppression of CD73 (sh-CD73) or control cells (sh-NT). We compared ZOL effects on tumor growth and infiltrating lymphocytes (TILs) into tumors and lung metastases using two mouse models. B cell depletion was performed using anti-CD20 antibody. Results: Sh-CD73 4T1 cells were significantly more sensitive to the growth inhibitory effects of n-BPs in vitro. However, while ZOL-induced growth inhibition was similar between the tumor groups in vivo, ZOL enhanced B and T lymphocyte infiltration into the orthotopic tumors with down-regulated CD73. A similar trend was detected in lung metastases. ZOL-induced tumor growth inhibition was found to be augmented with B cell depletion in sh-NT tumors, but not in sh-CD73 tumors. As an internal control, ZOL effects on bone were similar in mice bearing both tumor groups. Discussion: Taken together, these results indicate that ZOL modifies TILs in breast cancer, both in primary tumors and metastases. Our results further demonstrate that B cells may counteract the growth inhibitory effects of ZOL. However, all ZOL-induced TIL effects may be influenced by immunomodulatory characteristics of the tumor.

Published
2023

7. Immortalization of osteoclast precursors by targeting Bcl -XL and Simian virus 40 large T antigen to the osteoclast lineage in transgenic mice.

Author

Hentunen, T A, primary, Reddy, S V, additional, Boyce, B F, additional, Devlin, R, additional, Park, H R, additional, Chung, H, additional, Selander, K S, additional, Dallas, M, additional, Kurihara, N, additional, Galson, D L, additional, Goldring, S R, additional, Koop, B A, additional, Windle, J J, additional, and Roodman, G D, additional

Published
1998
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8. Characteristics of clodronate-induced apoptosis in osteoclasts and macrophages.

Author

Selander, K S, Mönkkönen, J, Karhukorpi, E K, Härkönen, P, Hannuniemi, R, and Väänänen, H K

Abstract

Bisphosphonates (BPs), such as clodronate and pamidronate, are inhibitors of bone resorption and are used on a widespread basis in the treatment of hyper-resorptive bone diseases. At the cellular level, BPs inhibit osteoclasts, but the precise molecular mechanisms are unclear. BPs have also been shown to affect the survival of macrophages, cells ontogenetically related to osteoclasts. We show that both clodronate and pamidronate induce apoptosis in isolated osteoclasts. Clodronate, when administered in liposomes, also induced apoptosis in rat peritoneal macrophages in vitro and in liver macrophages of mice in vivo but not in murine macrophage-like RAW-264 cells. The subcellular localization and staining intensity of Bcl-2, an anti-apoptotic protein known to protect several cell types against drug-induced apoptosis, were similar in RAW-264 and peritoneal macrophage cells, as revealed by immunofluorescence. The clodronate-induced apoptotic pathway was further characterized in isolated osteoclasts cultured on glass coverslips through the use of clodronate-containing liposomes and several inhibitors of the apoptotic cascade. None of the agents tested could totally prevent clodronate-induced osteoclast death. Partial protection was, however, obtained by the addition of staurosporine or homocysteine. The results suggest that primarily cytoplasmic, protein kinase C-activated mechanisms are involved in the execution of clodronate-induced apoptosis of osteoclasts.

Published
1996

11. Serum TRACP 5b and ICTP as markers of bone metastases in breast cancer.

Author

Korpela J, Tiitinen SL, Hiekkanen H, Halleen JM, Selander KS, Väänänen HK, Suominen P, Helenius H, and Salminen E

Subjects
Adult, Aged, Aged, 80 and over, Alkaline Phosphatase blood, Bone Neoplasms enzymology, Breast Neoplasms enzymology, Breast Neoplasms pathology, Collagen Type I, Cross-Sectional Studies, Female, Humans, Middle Aged, Peptides, Sensitivity and Specificity, Tartrate-Resistant Acid Phosphatase, Acid Phosphatase blood, Biomarkers, Tumor blood, Bone Neoplasms blood, Bone Neoplasms secondary, Breast Neoplasms blood, Isoenzymes blood, Peptide Fragments blood, Procollagen blood
Abstract

Background: The purpose of this cross-sectional study was to evaluate the value of serum tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal telopeptide of type I collagen (ICTP) separately and in combination as markers of bone metastases compared to total alkaline phosphatase (tALP) in breast cancer., Materials and Methods: Two groups of patients were studied, one with verfied bone metastases (N=46) and one without bone metastases (N=141). Bone marker levels were correlated with the presence or absence of bone metastases., Results: Serum TRACP 5b concentrations exhibited the largest area under the receiver-operating characteristics (ROC) curve (AUC=0.845), followed by ICTP (0.818) and tALP (0.814) when all patients were included in the analysis. With the combination of TRACP 5b and ICTP, the AUC increased to 0.881. In multivariate regression analysis, all three markers were significant predictors of bone metastases., Conclusion: Serum TRACP 5b, ICTP and tALP exhibited equal performances in the detection of bone metastases. The combination of TRACP with ICTP did not significantly improve the detection of bone metastases over tALP.

Published
2006

12. Short-term intravenous bisphosphonates in prevention of postmenopausal bone loss.

Author

Heikkinen JE, Selander KS, Laitinen K, Arnala I, and Väänänen HK

Subjects
Absorptiometry, Photon, Calcitriol blood, Calcium urine, Clodronic Acid administration & dosage, Clodronic Acid pharmacology, Collagen blood, Collagen Type I, Creatinine blood, Creatinine urine, Dose-Response Relationship, Drug, Double-Blind Method, Etidronic Acid administration & dosage, Etidronic Acid pharmacology, Female, Femur Neck drug effects, Femur Neck physiology, Follow-Up Studies, Humans, Hydroxyproline urine, Injections, Intravenous, Longitudinal Studies, Lumbar Vertebrae drug effects, Lumbar Vertebrae physiology, Middle Aged, Osteoporosis, Postmenopausal physiopathology, Peptide Fragments blood, Peptides blood, Procollagen blood, Prospective Studies, Bone Density drug effects, Clodronic Acid therapeutic use, Etidronic Acid therapeutic use, Osteoporosis, Postmenopausal prevention & control
Abstract

This study was performed to test the efficacy of short-term intravenous clodronate and etidronate in the prevention of postmenopausal bone loss. Healthy postmenopausal women, exhibiting a decreasing trend in bone mineral density, were randomized to five groups (clodronate at doses of 150, 300, and 600 mg; etidronate at a dose of 300 mg; and a placebo group) of 21-22 subjects. The drugs were administered intravenously three times with 1-week intervals, followed by regular evaluation for up to 24 months. During the first year, 300 mg of clodronate retarded bone loss significantly in the lumbar spine and femoral neck, where significant protection still persisted after 24 months. Other doses of clodronate (150 and 600 mg) were not bone protective. Etidronate (300 mg) retarded bone loss significantly in the lumbar spine up to 24 months, relative to placebo. Serum concentrations of procollagen I carboxy-terminal propeptide and urinary Ca2+ and hydroxyproline excretion decreased in all bisphosphonate groups during the first month after treatment, but the values returned later toward baseline. In the etidronate-group, serum osteocalcin concentrations also decreased significantly during the first 3 months of the study. Otherwise, no uniform serum responses to bisphosphonate-treatment were detected in circulating markers of bone formation, alkaline phosphatase, or osteocalcin. No significant differences in the serum concentrations of cross-linked carboxy-terminal telopeptide of type I collagen were detected between the groups. Patient acceptance of both bisphosphonates was excellent, and no drug-related adverse side effects were detected. These results suggest that infrequently repeated intravenous treatment with bisphosphonates may effectively counteract postmenopausal bone loss.

Published
1997
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