Breast cancer remains a significant female mortality cause. It constitutes a multifactorial disease for which research on environmental factors offers little help in predicting onset or progression. ...The pursuit for its foundations by analyzing hormonal changes as a motive for disease development, indicates that increased exposure to estrogens associates with increased risk. A prevalent number of breast cancer cases show dependence on the increased activity of the classic nuclear estrogen receptor (ER) for cell proliferation and survival. SIRT1 is a Type III histone deacetylase which is receiving increasing attention due to its ability to perform activities over relevant non-histone proteins and transcription factors. Interestingly, concomitant SIRT1 overexpression is commonly found in ER-positive breast cancer cases. Both proteins had been shown to directly interact, in a process related to altered intracellular signaling and aberrant transcription, then promoting tumor progression. Moreover, SIRT1 activities had been also linked to estrogenic effects through interaction with the G-protein coupled membrane bound estrogen receptor (GPER). This work aims to summarize present knowledge on the interplay between SIRT1 and ER/GPER for breast cancer onset and progression. Lastly, evidences on the ability of SIRT1 to interact with TGFß signaling, a concurrent pathway significantly involved in breast cancer progression, are reported. The potential of this research field for the development of innovative strategies in the assessment of orphan breast cancer subtypes, such as triple negative breast cancer (TNBC), is discussed.
Immune checkpoint inhibitors (ICIs) can improve survivals of metastatic triple negative breast cancer (mTNBC); however, we still seek circulating blood biomarkers to predict the efficacy of ICIs.
In ...this study, we analyzed the data of ICIs treated mTNBC collected in Anhui Medical University affiliated hospitals from 2018 to 2023. The counts of lymphocytes, monocytes, platelets, and ratio indexes (NLR, MLR, PLR) in peripheral blood were investigated via the Kaplan-Meier curves and the Cox proportional-hazards model.
The total of 50 mTNBC patients were treated with ICIs. High level of peripheral lymphocytes and low level of NLR and MLR at baseline and post the first cycle of ICIs play the predictable role of immunotherapies. Lymphocytes counts (HR = 0.280; 95% CI: 0.095-0.823; p = 0.021) and NLR (HR = 1.150; 95% CI: 1.052-1.257; p = 0.002) are significantly correlated with overall survival. High NLR also increases the risk of disease progression (HR = 2.189; 95% CI:1.085-4.414; p = 0.029). When NLR at baseline ≥ 2.75, the hazard of death (HR = 2.575; 95% CI:1.217-5.447; p = 0.013) and disease progression (HR = 2.189; 95% CI: 1.085-4.414; p = 0.029) significantly rise. HER-2 expression and anti-tumor therapy lines are statistically correlated with survivals.
Before the initiation of ICIs, enriched peripheral lymphocytes and poor neutrophils and NLR contribute to the prediction of survivals.
Water literacy has become a fundamental aspect in today’s society, as its conservation, preservation and management is key to ensuring human survival. The purpose of this paper was to analyze the ...effectiveness of flipped learning methodology on a traditional training practice in water literacy at the first level of secondary education. The flipped learning method consisted in providing the contents to the students before the class sessions, encouraging an active learning. A descriptive study was adopted with two experimental groups, two control groups and only post-test. An ad hoc questionnaire was used as an instrument to measure the parameters: Socio-educational, Motivation, Interactions, Autonomy, Collaboration; Deepening of contents; Problem solving, Class time and Ratings. The final sample was composed of 120 students, divided into four groups of 30 students each. The application of the treatment in the experimental groups lasted 10 sessions of 55 min. The results indicate that the use of time in class, the autonomy and the deepening of the contents were the aspects that improved most with the flipped learning approach. However, no significant differences in ratings were found. Finally, the main findings and their implications for water literacy are discussed.
For years, crop protection from pest attack, has been dominated by the use of synthetic insecticides. However, many of them can cause severe environmental problems and human health. In this context, ...the use of plant extracts constitutes an alternative to avoid this kind of contaminants. In this work, we investigated the chemical constituents and insecticidal activity of different extracts of leaves and stems of Argemone ochroleuca Sweet (Papaveraceae) against three economically important pests Sitophilos zeamais (Coleoptera:Curculionidae), Galleria mellonella (Lepidoptera:Pyralidae) and Xyleborus ferrugineus (Coleoptera:Scolytidae). A GC‐MS analysis mostly revealed the presence benzylisoquinoline alkaloids such as allocryptopine, protopine, among others. For the insecticidal activity, after nine hours of contact, the methanolic leaves extract showed a 100 % of mortality, followed by the dichloromethane stems extract with up to 93 % of mortality. The results suggest that the benzylisoquinoline alkaloids are involved in the insecticidal activity through the octopaminergic system of the tested insects.
An earlier analysis of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase ...inhibitor-resistant, hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) analysis.
Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2). OS was analysed in Cohort 2, the wild-type ESR1 population and the overall population. Additionally, we analysed subsequent systemic therapies and explored PFS2 (time from randomization to the end of the first subsequent therapy/death).
OS was 31.1 months for palbociclib plus fulvestrant and 32.8 months for capecitabine (adjusted hazard ratio aHR 1.10, 95% confidence interval CI 0.81–1.50, P = 0.550). In the wild-type ESR1 population, OS was 37.2 months for palbociclib plus ET and 34.8 months for capecitabine (aHR 1.06, 95% CI 0.81–1.37, P = 0.683). In OS analyses, no subgroup showed superiority for palbociclib plus ET over capecitabine. OS in the overall population was 32.6 months for palbociclib plus ET and 30.9 months for capecitabine (P = 0.995). Subsequent systemic therapy was given to 79.8% and 82.9% of patients with palbociclib plus ET and capecitabine, respectively. Median PFS2 was similar between study arms (Cohort 2, P = 0.941; wild-type ESR1 population, P = 0.827). No new safety findings were observed.
Palbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors.
NCT02028507 (ClinTrials.gov), 2013-003170-27 (EudraCT).
•Overall survival (OS) was assessed in patients with metastatic breast cancer (MBC).•OS was similar for palbociclib + fulvestrant and capecitabine in AI-resistant MBC.•The results were independent of the ESR1 mutational status.•In wild-type ESR1 tumours, palbociclib + ET and capecitabine also had similar OS.•Progression-free survival 2 was similar in both treatment arms.
Good teaching practices are developed in order to improve student learning. With technological and social development, educational practices increasingly demand the use of technology, so having good ...teaching practices with Information and Communication Technologies (ICT) is essential. At the same time, the Sustainable Development Agenda of the United Nations for the year 2030 is setting the principles of sustainable action for today’s society. In this context, the following objectives were proposed: to identify the good teaching practices with ICT that are being developed in Spanish higher education and to establish the relationship between good teaching practices with ICT and the Sustainable Development Goals (SDG). For this purpose, the method of systematic review of the literature based on the PRISMA protocol was used. A total of 27 documents published in the period 2008–2019 on good teaching practices with ICT in Spanish higher education were analyzed. Among the results, the emerging trend of good practices with ICT, the use of a Virtual Learning Environment (VLE) as the main technology in good practices, and the majority of good practices in the development of SDG #4 (Quality Education) are highlighted. Finally, it is a challenge for teachers to include all these aspects in their classroom teaching.
The predictive accuracy of the traditional staging system for cancer, the American Joint Committee on Cancer/Union Internationale Centre le Cancer (AJCC/UICC) classification of malignant tumors, is ...based on disease progression as a tumor cell-autonomous process, regardless the effects of the host immune response. The natural history of a tumor includes different phases of growth, migration and invasion. During these phases, tumor cells interact with their microenvironment and are influenced by signals from stromal, endothelial, inflammatory and immune cells. Indeed, tumors are often infiltrated by defensive cells such as lymphocytes, macrophages or mast cells and it has been shown extensively that lymphocytes may control cancer outcome, as evidenced in several human malignancies. Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based immunoscore (IS) has proved to be a prognostic factor in human malignancies such as colon, pancreas and lung cancer, hepatocellular carcinoma, melanoma and even brain metastases. Although the IS was initially established to evaluate the prognosis of stage I/II/III colon cancer patients, its association with clinical outcomes and survival has been shown in other malignancies. The aim of this review is to analyze the association of IS with prognosis, survival and response to therapy in different tumor types.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Background
Cytoreductive surgery (CRS) and administration of hyperthermic intraperitoneal chemotherapy (HIPEC) have shown their efficacy in multiple malignancies and also could offer a prognostic ...benefit for patients with advanced ovarian cancer.
Methods
A prospective, single-center, parallel-group, randomized phase 3 clinical trial analyzed patients with a diagnosis of carcinomatosis from ovarian cancer treated with neoadjuvant systemic chemotherapy (NACT). In this trial, 71 patients were randomized to receive CRS alone (36 patients) or CRS with HIPEC (35 patients) using cisplatin (75 mg/m
2
for 60 min at 42 °C). The primary end point was disease-free survival (DFS). Overall survival (OS), morbidity, and quality of life (QoL) were the secondary end points.
Results
During a median follow-up period of 32 months, the median DFS was 12 months in the control group (CRS) and 18 months in the experimental group (CRS and HIPEC). The findings showed HIPEC to be an independent protective factor against the development of recurrence (hazard ratio HR, 0.12, 95 % confidence interval CI, 0.02–0.89;
p
= 0.038). The median OS was 45 months in the control group and 52 months in the experimental group. The respective morbidity rates for any grade (1 to 5) were respectively 58.3 % and 45.7 % (
p
> 0.05), with a mortality rates of 2.8 % and 2.9 % (
p
> 0.05). In the dimensions evaluated, CRS with or without HIPEC had no impact on QoL.
Conclusions
For patients who had advanced ovarian cancer treated with NACT, CRS and HIPEC was associated with better DFS and OS, but without a difference in postoperative morbidity, mortality, or in the QoL evaluation.
Abstract
Objective
Analyze the cost contributors and their impact on the drug cost avoidance (DCA) resulting from cancer clinical trials over the period of 2015–2020 in a tertiary-level hospital in ...Spain (HCUVA).
Methods
We performed a cross-sectional, observational, retrospective study of a total of 53 clinical trials with 363 patients enrolled. We calculated the DCA from the price of the best standard of care (i.e.: drugs that the institution would otherwise fund). A linear regression model was used to determine cost contributors and estimate their impact.
Results
The total DCA was ~ 4.9 million euros (31 clinical trials; 177 enrollees), representing ~ 30% and ~ 0,05% approximately of the annual pharmaceutical expenditures at the HCUVA and for the Spanish Health System, respectively. Cancer type analysis showed that lung cancer had the highest average DCA by trial, indicating that treatments in these trials were the most expensive. Linear regression analysis showed that the number of patients in a trial did not significantly affect that trial's DCA. Instead, cancer type, phase trials, and intention of treatment were significant cost contributors to DCA. Compared to digestive cancer trials, breast and lung trials were significantly more expensive, (
p
< 0.05 and
p
< 0.1, respectively). Phase III trials were more expensive than Phase II (
p
< 0.01) and adjuvant trials were less expensive than palliative (
p
< 0.05).
Conclusion
We studied cost contributors that significantly impacted the estimated DCA from cancer clinical trials. Our work provides the groundwork to explore DCA contributors with potential to enhance public relations material and serve as a negotiating tool for budgeting, thus playing an important role to inform decisions about resource allocation.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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