scholarly journals Preclinical Evaluation of Ureidosulfamate Carbonic Anhydrase IX/XII Inhibitors in the Treatment of Cancers

2019 ◽  
Vol 20 (23) ◽  
pp. 6080 ◽  
Author(s):  
Kaye J. Williams ◽  
Roben G. Gieling
Keyword(s):  
Triple Negative ◽  
Ph Regulation ◽  
Treatment Resistance ◽  
Carbonic Anhydrases ◽  
Test Results ◽  
Future Studies ◽  
Clinical Phase ◽  
Chemical Structures ◽  
Catalytic Domains ◽  
Cancer Cell Type

Carbonic anhydrases (CAs) are a family of enzymes involved in the pH regulation of metabolically active cells/tissues. Upregulation of the CAIX/XII isoforms is associated with hypoxic tumours and clinically linked with malignant progression, treatment resistance and poor prognosis. The elucidation of the crystal structure of the catalytic domains of CAIX/XII provided the basis for the generation of CAIX/XII selective inhibitors based on the sulfonamide, sulfamate and coumarins chemical structures. Ureido-substituted benzenesulfonamide CAIX/XII inhibitors have shown significant potential, with U-104 (SLC-0111) currently present in clinical Phase I/II. Ureido-substituted sulfamate CAIX/XII inhibitors have received less attention despite encouraging preclinical test results. In triple-negative breast cancer (TNBC), ureidosulfamates revealed a significant antitumour (FC9-398A) and antimetastatic potential (S4). In small cell lung cancer (SCLC), a cancer cell type very sensitive to a dysregulation in CAIX signaling, S4 treatment was particularly effective when combined with cisplatin with no evidence of acquired cisplatin-resistance. These successful anticancer strategies should provide a solid basis for future studies on ureido-substituted sulfamates.

The effect of formula t-shirt method for scientists taught in science lessons in secondary schools on academic success

2020 ◽  
Vol 8 (S3) ◽  
pp. 1-10
Author(s):  
Burhan Karasu ◽  
Keyword(s):  
Academic Success ◽  
Secondary School ◽  
Item Analysis ◽  
Achievement Test ◽  
Test Results ◽  
Future Studies ◽  
Learning Techniques ◽  
Post Test ◽  
Research Findings ◽  
Experimental Group

The aim of this research is to investigate whether there is a meaningful difference in the academic success, between the students who are applied the "formula t-shirt method" (experimental group) and the students who are not (in other classes of the school), in the education for the scientists wanted to be taught in the secondary school 5th, 6th and 7th grade science textbooks. Semi-experimental method was used as research method. In the 6th grade, 27 students participated in this study as experimental group (students wearing t-shirts) and 49 students in the other classes of the school that did not participate in the study. Academic achievement test including pre-test and post-test, informative observations, students’ and teacher’s interviews as well as 20 printed t-shirts were used to collect data. The pilot study of the developed achievement test was applied in another school and also the item analysis of it was performed. According to the research findings, when the experimental group’s success post-test results from the application performed, were examined in line with the interviews, significant differences were observed. It was seen that the subjects aimed to be gained with the formula t-shirt method, were adopted by the students and also increased their success. Looking at the results of the research, thanks to wearing the t-shirts prepared by using the human body on the background, and the reconciliation of the students wearing with the scientists on t-shirts, the desired learning was provided. This also contributed to such learning techniques as peer learning, active learning, social learning in terms of visuality and integrity. It is thought that these materials developed with the formula t-shirt method, will also inspire researchers for future studies in terms of their usability in other fields and subjects

scholarly journals Do Children Benefit External Focus of Attention as Much as Adults? A Motor Learning Study

2017 ◽  
Vol 11 (7) ◽  
pp. 85 ◽  
Author(s):  
Somaye Roshandel ◽  
Hamidreza Taheri ◽  
Amir Moghadam
Keyword(s):  
Motor Skills ◽  
Retention Test ◽  
Attentional Focus ◽  
Focus Of Attention ◽  
Learning Study ◽  
Test Results ◽  
Future Studies ◽  
External Focus ◽  
Internal Focus ◽  
And Task

Recent evidence supports advantages of an external focus of attention on learning motor skills, however, there is a need to retest these finding for children and comparing them with adults. Thus, the purpose of current study was to determine the effect of different attentional focus on learning a motor skill in children and adults. Thirty children (8-12 year) and thirty adults (25-42 years) were randomly assigned to one of four groups: (1) Children external focus of attention (EFA), (2) Children- internal focus of attention (IFA), (3) Adults- External focus of attention (EFA), (4) Adults- internal focus of attention (IFA). Following initial instructions and task demonstration, participants performed 60 darts throwing in six blocks and 24 hours later performed 10 additional throws for retention test. Results revealed that children benefited from EFA and IFA instruction in the same manner, however, adults benefited from EFA more than IFA instruction. Future studies should continue to examine effects of different attentional focus on other skills.

scholarly journals Influence of Germline BRCA Genotype on the Survival of Patients with Triple-Negative Breast Cancer

2021 ◽  
Vol 1 (3) ◽  
pp. 140-147
Author(s):  
Cynthia Villarreal-Garza ◽  
Ana S. Ferrigno ◽  
Alejandro Aranda-Gutierrez ◽  
Paul H. Frankel ◽  
Nora H. Ruel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Point Mutations ◽  
Treatment Resistance ◽  
Cancer Center ◽  
Breast Cancers ◽  
Entire Cohort ◽  
Pathogenic Variants ◽  
Mutational Status

The presence of BRCA pathogenic variants (PV) in triple-negative breast cancer (TNBC) is associated with a distinctive genomic profile that makes the tumor particularly susceptible to DNA-damaging treatments. However, patients with BRCA PVs can develop treatment resistance through the appearance of reversion mutations and restored BRCA expression. As copy-number variants (CNV) could be less susceptible to reversion mutations than point mutations, we hypothesize that carriers of BRCA CNVs may have improved survival after treatment compared with carriers of other BRCA PVs or BRCA wild-type. Women diagnosed with stage I–III TNBC at ≤50 years at a cancer center in Mexico City were screened for BRCA PVs using a recurrent PV assay (HISPANEL; 77% sensitivity). Recurrence-free survival (RFS) and overall survival (OS) were compared according to the mutational status. Among 180 women, 17 (9%) were carriers of BRCA1 ex9–12del CNVs and 26 (14%) of other BRCA PVs. RFS at ten years for the whole cohort was 79.2% [95% confidence interval (CI), 72.3–84.6], with no significant differences according to mutational status. 10-year OS for the entire cohort was 85.3% (95% CI, 78.7–90.0), with BRCA CNV carriers demonstrating numerically superior OS rates other PV carriers and noncarriers (100% vs. 78.6% and 84.7%; log-rank P = 0.037 and P = 0.051, respectively). This study suggests that BRCA1 ex9–12del CNV carriers with TNBC may have a better OS, and supports the hypothesis that the genotype of BRCA PVs may influence survival by limiting treatment resistance mediated by reversion mutations among CNV carriers. Significance: Large CNV BRCA carriers in a cohort of young Mexican patients with TNBC had superior OS rates than carriers of other BRCA pathogenic variants (i.e., small indels or point mutations). We hypothesize that this is due to the resistance of CNVs to reversion mutations mediating resistance to therapy. If validated, these findings have important prognostic and clinical treatment implications for BRCA-associated breast cancers.

scholarly journals A Biomimetic Drug Delivery System Targeting Tumor Hypoxia in Triple-Negative Breast Cancers

2020 ◽  
Vol 10 (3) ◽  
pp. 1075 ◽  
Author(s):  
Katyayani Tatiparti ◽  
Mohd Ahmar Rauf ◽  
Samaresh Sau ◽  
Arun K. Iyer
Keyword(s):  
Triple Negative ◽  
Apoptotic Cell ◽  
Tumor Hypoxia ◽  
Chemical Properties ◽  
Treatment Resistance ◽  
Cell Killing ◽  
Cell Uptake ◽  
Cancer Drug ◽  
Breast Cancers

Triple-negative breast cancer (TNBC) is amongst the most challenging tumor subtypes because it presents itself without the estrogen, progesterone, and HER2 receptors. Hence, assessing new markers is an essential requirement for enhancing its targeted treatment. The survival of TNBC relies upon the advancement of hypoxia that contributes to treatment resistance, immune response resistance, and tumor stroma arrangement. Here, we explored bovine serum albumin (BSA) nanoparticle encapsulating the anti-cancer drug Paclitaxel (PTX) for cell-killing mediated by tumor hypoxia. For targeting hypoxia, we conjugated Acetazolamide (ATZ) with BSA nanoparticle that encapsulated PTX (referred hereon as BSA-PTX-ATZ) utilizing copper-free click chemistry, specifically the Strain-Promoted Alkyne Azide Cycloaddition (SPAAC). The in-vitro cell killing study uncovered that BSA-PTX-ATZ is more productive contrasted with free PTX. The evaluations of the physio-chemical properties of BSA-PTX-ATZ proves that the shelf-life is approximately two months when stored either at room or freezing temperatures or under refrigerated conditions. There is no leakage of PTX from the formulation during that period, while their nanoparticulate nature remained undisturbed. The BSA-PTX-ATZ nanoparticles indicated altogether higher cell killing in hypoxic conditions contrasted with normoxia proposing the hypoxia-mediated delivery mechanism of the activity of the formulation. Higher cell uptake found with fluorescent-marked BSA-PTX-ATZ shows CA-IX mediated cell uptake, substantiated by the prominent apoptotic cell death contrasted with free PTX.

scholarly journals Multispectral Contrast of Archaeological Features: A Quantitative Evaluation

2019 ◽  
Vol 11 (8) ◽  
pp. 913 ◽  
Author(s):  
Tuna Kalayci ◽  
Rosa Lasaponara ◽  
John Wainwright ◽  
Nicola Masini
Keyword(s):  
Quantitative Evaluation ◽  
Spectral Indices ◽  
Test Results ◽  
Precipitation Regime ◽  
Future Studies ◽  
Spectral Contrast ◽  
Simple Features ◽  
The Impact ◽  
The Relationship ◽  
Spectral Responses

This study provides an evaluation of spectral responses of hollow ways in Upper Mesopotamia. Hollow ways were used for the transportation of animals, carts, and other moving agents for centuries. The aim is to show how the success of spectral indices varies in describing topologically simple features even in a seemingly homogeneous geographic unit. The variation is further highlighted under the changing precipitation regime. The methodology begins with an exploration of the relationship between the date of a multispectral scene and the visibility of hollow ways. The next step is to evaluate the impact of rainfall levels on numerous indices and to quantify spectral contrast. The contrast between a hollow way and its background is evaluated with Welch’s t-test and the association between precipitation regime and spectral responses of hollow ways are investigated with Correspondence Analysis and Fisher’s test. Results highlight an intrinsic relationship between the precipitation regime and the ways in which archaeological features reflects and/or emits electromagnetic energy. Next, the categorization of spectral indices based on different rainfall levels can be used as a guidance in future studies. Finally, the study suggests contrast becomes an even more fruitful concept as one moves from the spatial domain to the spectral domain.

scholarly journals Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

2013 ◽  
Vol 12 (1) ◽  
pp. 11 ◽  
Author(s):  
Steven Rust ◽  
Sandrine Guillard ◽  
Kris Sachsenmeier ◽  
Carl Hay ◽  
Max Davidson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Type ◽  
Cancer Cell Type

scholarly journals Clinical research on new drugs (Phase I). Profile of scientific publications: data from the pre-clinical phase and bioethical aspects

2008 ◽  
Vol 23 (6) ◽  
pp. 531-535 ◽  
Author(s):  
Vanessa de Souza Brick ◽  
William Saad Hossne ◽  
Rogério Saad Hossne
Keyword(s):  
Data Collection ◽  
Phase I ◽  
New Drugs ◽  
Human Beings ◽  
Scientific Publications ◽  
Future Studies ◽  
Clinical Phase ◽  
Sample Characteristics ◽  
Phase Data ◽  
Phase Phase

PURPOSE: To trace a profile of scientific publications, phase I, in order to know whether or not they show pre-clinical phase data, emphasizing bioethical aspects. METHODS: Sixty-one scientific articles, published in 2007, involving research in human beings using new drugs, medicines and vaccines during phase I were analysed. A schedule for data collection was elaborated in which it would be possible to analyse and evaluate those articles. The schedule included items related to the pre-clinical phase associated to the clinical phase, and items related to the sample characteristics. RESULTS: Most of research works were carried out in USA. Taking into consideration that a large number of works have been dedicated to oncologic affections, most of them were carried out in voluntary ill individuals. Information on the pre-clinical phase, phase I, was very poor or absent. Even though some authors consider the phase I research as a promising one and also suggest some future studies on phase II, the reader is not able to consider the same way, as long as there is a shortage of information on the pre-clinical phase. CONCLUSION: The profile of scientific publications showed that data deserve some reflections and analysis to better evaluate the publications on phase I.

scholarly journals Tamoxifen Action in ER-Negative Breast Cancer

2016 ◽  
Vol 5 ◽  
pp. STI.S29901 ◽  
Author(s):  
Subrata Manna ◽  
Marina K. Holz
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Strategies ◽  
Tamoxifen Treatment ◽  
Breast Cancers ◽  
Future Studies ◽  
Aggressive Disease ◽  
Er Positive ◽  
Estrogen Related Receptor ◽  
Tamoxifen Sensitivity

Breast cancer is a highly heterogeneous disease. Tamoxifen is a selective estrogen receptor (ER) modulator and is mainly indicated for the treatment of breast cancer in postmenopausal women and postsurgery neoadjuvant therapy in ER-positive breast cancers. Interestingly, 5-10% of the ER-negative breast cancers have also shown sensitivity to tamoxifen treatment. The involvement of molecular markers and/or signaling pathways independent of ER signaling has been implicated in tamoxifen sensitivity in the ER-negative subgroup. Studies reveal that variation in the expression of estrogen-related receptor alpha, ER subtype beta, tumor microenvironment, and epigenetics affects tamoxifen sensitivity. This review discusses the background of the research on the action of tamoxifen that may inspire future studies to explore effective therapeutic strategies for the treatment of ER-negative and triple-negative breast cancers, the latter being an aggressive disease with worse clinical outcome.

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