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2. Real-world experience of second-line axitinib in metastatic renal cell carcinoma: analysis of the Swedish population.

Author

Jakobsson, Maria, Strambi, Angela, Nilsson, Fredrik, Arpegård, Johannes, and Dalén, Johan

Abstract

Aim: Assess the time-to-treatment discontinuation (TTD) and overall survival (OS) in a Swedish metastatic renal cell carcinoma (mRCC) nationwide cohort who received second-line axitinib. Methods: Retrospective analysis of 110 patients with mRCC treated with second-line axitinib in Sweden (2012–2019). Patients included in the study received axitinib after mainly first-line sunitinib or pazopanib. Results: The median (95% CI) TTD of patients who received second-line axitinib was 5.2 (3.7–6.1) months with 6 (5.5%) patients still receiving treatment at the time of analysis. Median (95% CI) OS was 12.2 (7.7–14.2) months. Conclusion: The results are consistent with previous findings in mRCC and add to the evidence demonstrating efficacy of second-line axitinib, after failure of a prior anti-angiogenic therapy in a real-world setting. Clinical Trial Registration:NCT04669366 (ClinicalTrials.gov) Article highlights The aim of this study was to assess the time-to-treatment discontinuation (TTD) and overall survival (OS) in a Swedish metastatic renal cell carcinoma (mRCC) national cohort who received second-line axitinib. A retrospective analysis of patients with mRCC treated with second-line axitinib in Sweden (2012–2019). A total of 110 patients with mRCC received second-line treatment with axitinib in the full population; 53 patients received first-line sunitinib, 53 patients received first-line pazopanib and the remaining four patients received another permitted first-line treatment. The median (95% CI) TTD in patients who received second-line axitinib was 5.2 (3.7–6.1) months with 6 (5.5%) patients still receiving treatment at the time of analysis. The median OS (95% CI) for all patients who received second-line axitinib was 12.2 (7.7–14.2) months; 28 (25.5%) patients remained censored at the time of analysis. The results are consistent with previous findings in mRCC and add to the evidence demonstrating efficacy of second-line axitinib, after failure of a prior anti-angiogenic therapy in a real-world setting. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Relationship between the excited state relaxation paths of Rhodopsin and Isorhodopsin

Author

Strambi, Angela, Coto, Pedro B., Frutos, Luis Manuel, Ferre, Nicolas, and Olivucci, Massimo

Subjects
Excited state chemistry -- Research, Quantum theory -- Research, Rhodopsin -- Chemical properties, Rhodopsin -- Structure, Chemistry
Abstract

The pigment Isorhodopsin, an analogue of the visual pigment Rhodopsin, is examined by using quantum-mechanical/molecular-mechanics computations that is based on an ab initio multiconfigurational quantum chemical treatment. The results have shown that Rhodopsin and Isorhodopsin have relaxed along a common excited-state potential energy valley starting from opposite ends.

Published
2008

12. EGFR-Targeted Magnetic Nanovectors Recognize, in Vivo, Head and Neck Squamous Cells Carcinoma-Derived Tumors

Author

Colecchia, David, primary, Nicolato, Elena, additional, Ravagli, Costanza, additional, Faraoni, Paola, additional, Strambi, Angela, additional, Rossi, Matteo, additional, Doumett, Saer, additional, Mosconi, Elisa, additional, Locatelli, Erica, additional, Comes Franchini, Mauro, additional, Balzi, Manuela, additional, Baldi, Giovanni, additional, Marzola, Pasquina, additional, and Chiariello, Mario, additional

Published
2017
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17. Protein Influence on Electronic Spectra Modeled by Multipoles and Polarizabilities

Author

Söderhjelm, Pär, Husberg, Charlotte, Strambi, Angela, Olivucci, Massimo, Ryde, Ulf, Söderhjelm, Pär, Husberg, Charlotte, Strambi, Angela, Olivucci, Massimo, and Ryde, Ulf

Abstract

We have developed automatic methods to calculate multipoles and anisotropic polarizabilities for all atoms and bond centers in a protein and to include such a model in the calculation of electronic properties at any level of quantum mechanical theory. This approach is applied for the calculation of the electronic spectra of retinal in rhodopsin at the CASPT2//CASSCF level (second-order multiconfigurational perturbation theory) for the wild-type protein, as well as two mutants and isorhodopsin in QM/MM structures based on two crystal structures. We also perform a detailed investigation of the importance and distance dependence of the multipoles and the polarizabilities for both the absolute and the relative absorption energies. It is shown that the model of the surrounding protein strongly influences the spectrum and that different models give widely different results. For example, the Amber 1994 and 2003 force fields give excitation energies that differ by up to 16 kJ/mol. For accurate excitation energies, multipoles up to quadrupoles and anisotropic polarizabilities are needed. However, interactions with residues more than 10 A from the chromophore can be treated with a standard polarizable force field without any dipoles or quadrupoles.

Published
2009

21. EGFR-Targeted Magnetic Nanovectors Recognize, in Vivo, Head and Neck Squamous Cells Carcinoma-Derived Tumors

Author

Pasquina Marzola, Mario Chiariello, Saer Doumett, Mauro Comes Franchini, Angela Strambi, David Colecchia, Elena Nicolato, Matteo Rossi, Erica Locatelli, Costanza Ravagli, Manuela Balzi, Paola Faraoni, Giovanni Baldi, Elisa Mosconi, Colecchia, David, Nicolato, Elena, Ravagli, Costanza, Faraoni, Paola, Strambi, Angela, Rossi, Matteo, Doumett, Saer, Mosconi, Elisa, Locatelli, Erica, Comes Franchini, Mauro, Balzi, Manuela, Baldi, Giovanni, Marzola, Pasquina, and Chiariello, Mario

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, magnetite, medicine.drug_class, EGFR, Cell, Monoclonal antibody, HNSCC, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, In vivo, Drug Discovery, medicine, Carcinoma, Epidermal growth factor receptor, Receptor, biology, business.industry, Kinase, nanoparticle, Drug Discovery3003 Pharmaceutical Science, Organic Chemistry, medicine.disease, In vitro, targeting delivery systems, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, biology.protein, nanoparticles, business, targeting delivery system
Abstract

Head and neck squamous cell carcinomas (HNSCC) are a diverse group of tumors with high morbidity and mortality that have remained mostly unchanged over the past decades. The epidermal growth factor receptor (EGFR) is often overexpressed and activated in these tumors and strongly contributes to their pathogenesis. Still, EGFR-targeted therapies such as monoclonal antibodies and kinase inhibitors have demonstrated only limited improvements in the clinical outcome of this disease. Here, we take advantage of the extraordinary affinity of EGF for its cognate receptor to specifically target magnetite-containing nanoparticles to HNSCC cells and mediate, in vitro, their cellular upload. On the basis of this, we show efficient accumulation, in vivo, of such nanoparticles in subcutaneous xenograft tumor tissues in sufficient amounts to be able to mediate visualization by magnetic resonance imaging. Overall, our EGF-coated nanosystem may warrant, in the near future, novel and very efficient theranostic approaches to HNSCC.

Published
2017
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22. MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors

Author

Angela Strambi, Mario Chiariello, Mario Acunzo, Matteo Rossi, Federica Sasdelli, Gennaro Ilardi, Giovanni Nigita, Stefania Staibano, Angela Celetti, David Colecchia, Carlo M. Croce, Rossi, Matteo, Colecchia, David, Ilardi, Gennaro, Acunzo, Mario, Nigita, Giovanni, Sasdelli, Federica, Celetti, Angela, Strambi, Angela, Staibano, Stefania, Croce, Carlo Maria, and Chiariello, Mario

Subjects
embryonal carcinoma, 0301 basic medicine, p53, Male, Transcriptional Activation, autophagy, DNA damage, Mice, Nude, Endogeny, Apoptosis, Biology, Malignant transformation, 03 medical and health sciences, Mice, Downregulation and upregulation, Testicular Neoplasms, medicine, Biomarkers, Tumor, Tumor Cells, Cultured, Animals, Humans, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, embryonal carcinomas, Cell growth, Cell Cycle, Cell cycle, Neoplasms, Germ Cell and Embryonal, medicine.disease, Xenograft Model Antitumor Assays, Up-Regulation, 030104 developmental biology, MAP kinases, Oncology, Immunology, Cancer research, MAP kinase, Female, Germ cell tumors, Tumor Suppressor Protein p53, Research Paper
Abstract

Germ cell tumors (GCT) are the most common malignancies in males between 15 and 35 years of age. Despite the high cure rate, achieved through chemotherapy and/or surgery, the molecular basis of GCT etiology is still largely obscure. Here, we show a positive correlation between MAPK15 (ERK8; ERK7) expression and specific GCT subtypes, with the highest levels found in the aggressive embryonal carcinomas (EC). Indeed, in corresponding cellular models for EC, MAPK15 enhanced tumorigenicity in vivo and promoted cell proliferation in vitro, supporting a role for this kinase in human GCT. At molecular level, we demonstrated that endogenous MAPK15 is necessary to sustain cell cycle progression of EC cells, by limiting p53 activation and preventing the triggering of p53-dependent mechanisms resulting in cell cycle arrest. To understand MAPK15-dependent mechanisms impinging on p53 activation, we demonstrate that this kinase efficiently protects cells from DNA damage. Moreover, we show that the ability of MAPK15 to control the autophagic process is necessary for basal management of DNA damage and for tumor formation controlled by the kinase. In conclusion, our findings suggest that MAPK15 overexpression may contribute to the malignant transformation of germ cells by controlling a "stress support" autophagic pathway, able to prevent DNA damage and the consequent activation of the p53 tumor suppressor. Moreover, in light of these results, MAPK15-specific inhibitors might represent new tools to enhance the therapeutic index of cytotoxic therapy in GCT treatment, and to increase the sensitivity to DNA-damaging drugs in other chemotherapy-resistant human tumors.

Published
2016
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23. First-line sunitinib treatment modification in patients with mRCC: nationwide analysis of the Swedish population.

Author

Jakobsson M, Nilsson F, Strambi A, Arpegård J, and Dalén J

Subjects
Humans, Sweden epidemiology, Female, Male, Middle Aged, Retrospective Studies, Aged, Adult, Antineoplastic Agents therapeutic use, Antineoplastic Agents administration & dosage, Aged, 80 and over, Treatment Outcome, Drug Administration Schedule, Sunitinib therapeutic use, Sunitinib administration & dosage, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell pathology, Kidney Neoplasms drug therapy, Kidney Neoplasms mortality, Kidney Neoplasms pathology
Abstract

Aim: Assess first-line sunitinib dosing for treatment of metastatic renal cell carcinoma in Swedish clinical practice (2006-2019). Materials & methods: Retrospective analysis of three sunitinib dosing regimens: 2-weeks on, 1-week off (2:1 Start); standard 4-weeks on, 2-weeks off (4:2) and 4:2 start with switch to 2:1 (2:1 Switch). Results: Time-to-treatment discontinuation (95% CI) differed significantly ( p  < 0.001): 6.2 (5.6-7.2), 13.9 (8.1-20.6) and 4.6 (4.3-5.6) months for 2:1 Start ( n  = 320), 2:1 Switch ( n  = 71) and 4:2 ( n  = 704), respectively. Overall survival (95% CI) differed significantly ( p  < 0.001): 21.8 (18.1-26.1), 32.2 (25.1-48.3) and 13.5 (12.3-15.8) months for 2:1 Start ( n  = 320), 2:1 Switch ( n  = 71) and 4:2 ( n  = 704), respectively. Conclusion: Alternative dosing does not compromise clinical efficacy and may provide advantages in terms of improved treatment outcomes. However, due to the changing treatment patterns during this long-term study, and the absence of patient risk category data, caution is required when interpreting the main outcomes.

Published
2024
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