A CHANGE OF PERSPECTIVE: CZESŁAW MIŁOSZ’S POETRY AND ITS FIRST RECEPTION
In the criticism and studies of Czesław Miłosz’s work, the cycles “The world (naive poem)” and “Voices of the poor people”, ...from the book Rescue (1945) occupy a place of enormous importance because it opens two lines of the postwar Polish poetry, initiates the so-called polyphony of the Polish author and establishes links with other literary traditions, especially the Anglo-Saxon and T. S. Eliot’s poem The Waste Land. But these elements should not necessarily always be kept in a translation, rather they can lead to other reminiscences. In the article, we study this fenomen based on the theories of Antoine Berman and focused in the first published translation of the Polish author’s poems in Spanish.
In the criticism and studies of Czesaw Mioszs work, the cycles The world (naive poem) and Voices of the poor people, from the book Rescue (1945) occupy a place of enormous importance because it opens ...two lines of the postwar Polish poetry, initiates the so-called polyphony of the Polish author and establishes links with other literary traditions, especially the Anglo-Saxon and T. S. Eliots poemThe Waste Land. But these elements should not necessarily always be kept in a translation, rather they can lead to other reminiscences. In the article, we study this fenomen based on the theories of Antoine Berman and focused in the first published translation of the Polish authors poems in Spanish.
The present mini essay analyses the literary output of Tomasz Różycki, a Polish poet belonging to the middle generation, who occupies now the central position among the poets of his generation. ...Różycki diverges from other poets because of his specific understanding of the poetic tradition and its development in modern times.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Orally administered synthetic cannabinoids (nabilone and dronabinol) have been shown to be superior to dopamine receptor antagonists in preventing ...chemotherapy‐induced nausea and vomiting (CINV).
• There is no information on the tolerability of an acute dose titration of a whole‐plant cannabis‐based medicine (CBM).
• The efficacy of cannibidiol with tetrahydrocannabinol added to the current standard therapy in the control of CINV after moderately emetic cancer chemotherapy (MEC) administration has not been established.
WHAT THIS STUDY ADDS
• This is the first controlled study assessing the tolerability of an acute dose titration of a CBM.
• The results suggest that rapid titration of a CBM appeared to be well tolerated by most patients and efficacious in reducing the incidence of delayed CINV.
AIMS
Despite progress in anti‐emetic treatment, many patients still suffer from chemotherapy‐induced nausea and vomiting (CINV). This is a pilot, randomized, double‐blind, placebo‐controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole‐plant cannabis‐based medicine (CBM) containing delta‐9‐tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV.
METHODS
Patients suffering from CINV despite prophylaxis with standard anti‐emetic treatment were randomized to CBM or placebo, during the 120 h post‐chemotherapy period, added to standard anti‐emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response.
RESULTS
Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period 5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%), due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups.
CONCLUSION
Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial.
There are many levels of lecture of the The Newcomers, a novel by Slovenian writer Lojze Kovačič. The protagonist, Alojz, lives in a fragmented and rootless world, undertaking a physical and ...spiritual journey. The novel, of a clearly autobiographical character, is written in Slovenian, a language that the author learned when he was 12 years old and which he later adopted for his creation. The foreignness of the experience of life is therefore reflected by the exoticism of the language. The article reflects on the technique of transferring this exoticism into the Spanish translation of this novel.
Abstract
Despite the genetic inactivation of
SMARCA4
, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. ...Here, we show that, unlike the cells with activated
MYC
oncogene, cells with
SMARCA4
inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3.
SMARCA4
-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with
SMARCA4
-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating
SMARCA4-
mutant cancer patients.
Prostate cancer (PCa) was the second most frequent cancer and the fifth leading cause of cancer death among men in 2020. The aim of this study was to analyze trends in the incidence, mortality and ...survival of PCa in Girona, Spain, over 25 years.
Population-based study of PCa collected in the Girona Cancer Registry, 1994-2018. Age-adjusted incidence and mortality rates were calculated per 100,000 men-year. Joinpoint regression models were used for trends, calculating the annual percentage changes (APC). Observed and net survival were analyzed using Kaplan-Meier and Pohar-Perme estimations, respectively.
A total of 9,846 cases of PCa were registered between 1994-2018. The age-adjusted incidence and mortality rates were 154.7 (95%CI: 151.7 157.8) and 38.9 (95%CI: 37.3 -40.6), respectively. An increased incidence of 6.2% was observed from 1994 to 2003 (95%CI: 4.4 -8.1), and a decrease of -2.7% (95%CI: -3.5 -;-1.9) between 2003 and 2018. Mortality APC was -2.6% (95%CI: -3.3 --2.0). Five-year observed and net survival were 72.8% (95%CI: 71.8 - 73.7) and 87.2% (95%CI: 85.9 - 88.4), respectively. Five-year net survival increased over time from 72.9% (1994-1998) to 91.3% (2014-2018).
The analyses show a clear reduction in PCa incidence rates from 2003 on, along with an increase in overall survival when comparing the earlier period with more recent years.
The biological effect of oral metronomic vinorelbine (mVNB) alone or in combination with endocrine therapy in patients with hormone receptor-positive (HR+)/HER2-negative breast cancer has been ...scarcely addressed.
Postmenopausal women with untreated stage I-III HR+/HER2-negative breast cancer were randomized (1:1:1) to receive 3 weeks of letrozole (LTZ) 2.5 mg/day, oral mVNB 50 mg 3 days/week, or the combination. The primary objective was to evaluate, within PAM50 Luminal A/B disease, if the anti-proliferative effect of LTZ+mVNB was superior to monotherapy. An anti-proliferative effect was defined as the mean relative decrease of the PAM50 11-gene proliferation score in combination arm vs. both monotherapy arms. Secondary objectives included the evaluation of a comprehensive panel of breast cancer-related genes and safety. An unplanned analysis of stromal tumor-infiltrating lymphocytes (sTILs) was also performed. PAM50 analyses were performed using the nCounter®-based Breast Cancer 360™ gene panel, which includes 752 genes and 32 signatures.
Sixty-one patients were randomized, and 54 paired samples (89%) were analyzed. The main patient characteristics were mean age of 67, mean tumor size of 1.7 cm, mean Ki67 of 14.3%, stage I (55.7%), and grades 1-2 (90%). Most baseline samples were PAM50 Luminal A (74.1%) or B (22.2%). The anti-proliferative effect of 3 weeks of LTZ+mVNB (- 73.2%) was superior to both monotherapy arms combined (- 49.9%; p = 0.001) and mVNB (- 19.1%; p < 0.001). The anti-proliferative effect of LTZ+mVNB (- 73.2%) was numerically higher compared to LTZ (- 65.7%) but did not reach statistical significance (p = 0.328). LTZ+mVNB induced high expression of immune-related genes and gene signatures, including CD8 T cell signature and PDL1 gene and low expression of ER-regulated genes (e.g., progesterone receptor) and cell cycle-related and DNA repair genes. In tumors with ≤ 10% sTILs at baseline, a statistically significant increase in sTILs was observed following LTZ (paired analysis p = 0.049) and LTZ+mVNB (p = 0.012). Grade 3 adverse events occurred in 3.4% of the cases.
Short-term mVNB is well-tolerated and presents anti-proliferative activity alone and in combination with LTZ. The high expression of immune-related biological processes and sTILs observed with the combination opens the possibility of studying this combination with immunotherapy. Further investigation comparing these biological results with other metronomic schedules or drug combinations is warranted.
NCT02802748 , registered 16 June 2016.
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