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Etoposide and topoisomerase II inhibition for aggressive prostate cancer: Data from a translational study
No full textBackground: Etoposide phosphate (VP-16) is a topoisomerase 2 (TOP2) inhibitor that demonstrated activity in patients with metastatic castration-resistant prostate cancer (mCRPC). We investigated the sensitivity of prostate cancer (PCa) cells (LNCaP, 22Rv1, PC3, DU145, PDB and MDB) to VP-16 and the possible relationship between VP-16 activity and TOP2 expression. The activity of VP-16 was compared with that of docetaxel, enzalutamide and olaparib. The prevalence and clinical significance of TOP2 genetic and transcriptomic alterations was also explored in mCRPC. Methods: Cell cultures and crystal violet cell proliferation assays were performed. Specific antibodies were used in western blots analyses of cell protein extracts. Datasets were analyzed in cBioportal. Results: VP-16 was active in all PCa cell lines analyzed and demonstrated increased activity in PC3 and DU145 cells. VP-16 was more cytotoxic compared to the other treatments, except for LNCaP and 22Rv1, which were more sensitive to docetaxel. Maintenance of antiandrogen treatment in MDB and PDB increased sensitivity to VP-16, docetaxel and enzalutamide. TOP2A was found overexpressed in 22Rv1, DU145 and PC3, whereas TOP2B was overexpressed in 22Rv1 and PDB. In the mCRPC datasets analysis, TOP2A mRNA overexpression was associated with worse patients’ prognosis, with the molecular features of neuroendocrine prostate cancer (NEPC) and with lower androgen receptor (AR) score. Patients overexpressing TOP2A mRNA were more likely to harbor RB1 loss. Conclusions: Specific subpopulations of patients with aggressive variant prostate cancer (AVPC) could benefit from VP-16 treatment. TOP2A overexpression, rather than TOP2B, might be a good biomarker to predict response to VP-16
Medical Liability in Cancer Care During COVID-19 Pandemic: Heroes or Guilty?
No full textBackground: The COVID-19 outbreak rapidly became a public health emergency affecting particularly the frail category as cancer patients. This led oncologists to radical changes in patient management, facing the unprecedent issue whether treatments in oncology could be postponed without compromising their efficacy. Purpose: To discuss legal implications in oncology practice during the COVID-19 pandemic. Perspective: Treatment delay is not always feasible in oncology where the timing often plays a key role and may impact significantly in prognosis. During the COVID-19 pandemic, the oncologists were found between the anvil and the hammer, on the one hand the need to treat cancer patients aiming to improve clinical benefits, and on the other hand the goal to reduce the risk of COVID-19 infection avoiding or delaying immunosuppressive treatments and hospital exposure. Therefore, two rising scenarios with possible implications in both criminal and civil law are emerging. Firstly, oncologists may be “accused” of having delayed or omitted the diagnosis and/or treatments with consequent worsening of patients' outcome. Secondly, oncologists can be blamed for having exposed patients to hospital environment considered at risk for COVID-19 transmission. Conclusions: During the COVID-19 pandemic, clinical decision making should be well-balanced through a careful examination between clinical performance status, age, comorbidities, aim of the treatment, and the potential risk of COVID-19 infection in order to avoid the risk of suboptimal cancer care with potential legal repercussion. Moreover, all cases should be discussed in the oncology team or in the tumor board in order to share the best strategy to adopt case by case
A large SEER- based study of survival trends in patients with de novo metastatic prostate cancer
No full textComments on “Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476)
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Antiangiogenic tyrosine kinase inhibitors and immunotherapy as first-line treatment for metastatic renal cell carcinoma: is there an increased risk of hypothyroidism?
No full textEFFICACY AND SAFETY OF SUNITINIB AND EVEROLIMUS AS FRONTLINE TREATMENT FOR NON-CC-RCC: A POOLED-ANALYSIS FROM RANDOMIZED TRIALS
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Real-world survival improvements in patients with newly diagnosed metastatic prostate cancer treated in the United States
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