The effects of low doses of pregabalin on morphine analgesia in advanced cancer patients

Abstract OBJECTIVES: The aim of this study was to evaluate the opioid response in patients receiving morphine and pregabalin, independently from the presumed pain mechanisms, in comparison with patients receiving morphine treatment only. METHODS: A multicenter prospective randomized controlled study was carried out in a sample of 70 advanced cancer patients with pain requiring strong opioids. Thirty-five patients (group MO) were randomized to receive sustained-release morphine using initial doses of 60 mg/day. Thirty-five patients (group MO-PR) were randomized to start the same morphine doses and pregabalin in increasing doses, starting with 25 mg/day up to 150 mg/day in one week. The following data were also recorded before starting the treatments (T0) and then at week intervals for four weeks (W1-4): age, gender, primary cancer and known metastases, pain causes and mechanisms, symptoms associated with opioid therapy, pain intensity, Brief Pain Inventory (BPI), morphine doses and escalation indexes (OEIs), and quality of life. RESULTS: Forty-eight patients completed the study, twenty-eight and sixteen patients in group MO and MO-PR, respectively. Twenty patients were females, the mean age was 65.5 (± 10.3), and the mean Karnofsky status was 66.0 (± 18.9). No differences between groups were found in age (P = 0.839), Karnofsky status (P = 0.741), opioid doses as well as escalation indexes (OEI mg, P = 0.260, and OEI%, P = 0.270). No differences between the two groups were found in quality of life and all BPI items. CONCLUSION: The use of low doses of pregabalin added to morphine therapy in advanced cancer patients does not seem to provide advantageous analgesic effects, despite limitations of the present study due to the number of drop-outs

CD44: A New Prognostic Marker in Colorectal Cancer?

Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial–mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications

Early taxane exposure and neurotoxicity in breast cancer patients

Introduction: Breast cancer is the most diagnosed tumor and a leading cause of cancer death in women worldwide. Taxanes are the most used chemotherapeutic agents and are strictly connected to neurotoxicity. Taxane-induced neuropathy (TIN) significantly impacts patients' quality of life (QOL). Early identification and management of TIN could improve preventive strategies to preserve patients' QOL during and after breast cancer treatment. Objective: This prospective, observational study aimed to evaluate the taxane-induced neuropathy (TIN) in early breast cancer patients treated with weekly paclitaxel at an earlier stage and identify any correlation between TIN and QOL. Methods: Data from stage I-III breast cancer patients treated with taxane-based therapy between 2018 and 2022 were collected at the Medical Oncology Unit of the University Hospital of Cagliari. Peripheral neuropathy was evaluated using the NCI-CTCAE scale (National Cancer Institute, Common Terminology Criteria for Adverse Events) at every drug administration. In contrast, QOL was assessed using EORTC QLC-CIPN20 and FACT-Taxane questionnaire at baseline (T0), after 4 weeks (T1) and 12 (T2) weeks of treatment. Statistical analysis was performed to evaluate the correlation between neurotoxicity and QOL. Results: Neurotoxicity incidence peaked at the third, fourth, and sixth week of treatment, with patients reporting grade 1 and 2 neurotoxicity. Simultaneously with increasing doses of paclitaxel, significant differences in QOL were observed in early treatment cycles relating to TIN presentation. Patients with higher neurotoxicity grades reported lower QOL scores. Conclusions: Despite the absence of effective treatments to prevent paclitaxel-induced neurotoxicity, symptoms are managed through dosage reduction, delay, or treatment interruption. Future research should focus on identifying neuroprotective measures to avoid an irreversible decline in the quality of life for breast cancer survivors

CD44: A New Prognostic Marker in Colorectal Cancer?

Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial-mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications

Early taxane exposure and neurotoxicity in breast cancer patients

Introduction Breast cancer is the most diagnosed tumor and a leading cause of cancer death in women worldwide. Taxanes are the most used chemotherapeutic agents and are strictly connected to neurotoxicity. Taxane-induced neuropathy (TIN) significantly impacts patients’ quality of life (QOL). Early identification and management of TIN could improve preventive strategies to preserve patients’ QOL during and after breast cancer treatment. Objective This prospective, observational study aimed to evaluate the taxane-induced neuropathy (TIN) in early breast cancer patients treated with weekly paclitaxel at an earlier stage and identify any correlation between TIN and QOL. Methods Data from stage I-III breast cancer patients treated with taxane-based therapy between 2018 and 2022 were collected at the Medical Oncology Unit of the University Hospital of Cagliari. Peripheral neuropathy was evaluated using the NCI-CTCAE scale (National Cancer Institute, Common Terminology Criteria for Adverse Events) at every drug administration. In contrast, QOL was assessed using EORTC QLC-CIPN20 and FACT-Taxane questionnaire at baseline (T0), after 4 weeks (T1) and 12 (T2) weeks of treatment. Statistical analysis was performed to evaluate the correlation between neurotoxicity and QOL. Results Neurotoxicity incidence peaked at the third, fourth, and sixth week of treatment, with patients reporting grade 1 and 2 neurotoxicity. Simultaneously with increasing doses of paclitaxel, significant differences in QOL were observed in early treatment cycles relating to TIN presentation. Patients with higher neurotoxicity grades reported lower QOL scores. Conclusions Despite the absence of effective treatments to prevent paclitaxel-induced neurotoxicity, symptoms are managed through dosage reduction, delay, or treatment interruption. Future research should focus on identifying neuroprotective measures to avoid an irreversible decline in the quality of life for breast cancer survivors

Pointer years and growth in Turkey oak (Quercus cerris L) in Latium (central Italy). A dendroclimatic approach

International audienc

Pointer years and growth in Turkey oak (Quercus cerris L) in Latium (central Italy). A dendroclimatic approach

A dendrochronological and a dendroclimatological analysis was carried out on samples of Turkey oak from seven sites in Latium. This research was effected in order to investigate what climatic impulse makes the dendrochronological curves of different sites comparable to each other. The Latium region proved particularly suitable for this kind of analysis due to its many orographic, climatic and pedologic differences within distances of a few kilometres. Pointer years were checked on the residuals curves and on the raw data taking into account the same growth trend for consecutive years. The dendroclimatic analysis showed that the majority of pointer years are related to spring precipitation and to June temperature. In addition, a preliminary approach is reported to define some anatomical features of pointer years. An automatic image analysis system was used to examine anatomical features in pointer years and a new method for histological quantitative representation is proposed.Années caractéristiques et accroissement du chêne chevelu (Quercus cerris L) dans le Latium (Italie centrale). Une approche dendroclimatique. Une analyse dendrochronologique et dendroclimatologique a été menée sur quelques échantillons de Quercus cerris prélevés dans sept sites du Latium. L'objectif majeur de l'analyse est d'identifier les facteurs climatiques qui rendent comparables entre elles les courbes dendrochronologiques correspondant aux différents sites prospectés. La région prospectée fournit des situations orographiques, pédologiques et climatiques variables sur de courtes distances. Les années caractéristiques sont déterminées par l'analyse des tendances de croissances communes. Il résulte de l'analyse dendroclimatique que la plupart des années caractéristiques sont en relation directe avec les précipitations de printemps et en relation inverse avec les températures de juin. Par ailleurs, un premier essai de caractérisation anatomique des années caractéristiques par analyse d'image a été réalisé et une nouvelle méthode de description histologique quantitative a été testée

Road safety analysis: a study on the visual perception of road signs using a rriving simulator

Driver’s visual perception is among the human factors that most influence road safety. A driver who does not correctly perceive external inputs can increase the probability of an accident to occur. This research intends to contribute to active safety studies by analyzing how the perception of vertical road signs in urban area may vary under “standard” traffic and visibility conditions, for drivers in various age groups. To understand the visual perception of vertical signs, a simulation experiment was conducted in which a sample of drivers traveled an urban route using a car simulator. From the results it emerges that vertical signs are very rarely observed by drivers: on average, only one sign in five was seen. The data collected show a frequency observation of vertical signs between 100 ms and 500 ms, with an average observation time of 200 ms. No one sign class was observed more than others, and the observation rates were very low (<20%) for all sign classes. The results may help identify future applications to improve the visibility and perception of vertical road signs in urban areas