Effect of Carboxylesterase Inhibition on the Anti-Tumour Effects of Irinotecan

2005 ◽  
Vol 33 (1) ◽  
pp. 84-89 ◽  
Author(s):  
Y Morishita ◽  
M Fujii ◽  
Y Kasakura ◽  
T Takayama
Keyword(s):  
Growth Rate ◽  
Adverse Effects ◽  
Nude Mice ◽  
Anticancer Agent ◽  
Specific Inhibitor ◽  
Optimal Dose ◽  
Optimum Dose ◽  
The Relationship ◽  
Opening Up ◽  
Individualized Chemotherapy

Irinotecan (CPT-11) is an important anticancer agent activated by carboxylesterase (CE). Treatment with CPT-11 may be associated with severe adverse effects, however, so determining the optimal dose would greatly benefit patients. We investigated the relationship between the anti-tumour effects of CPT-11 and CE concentration using bis- p-nitrophenylphosphate (BNPP), a specific inhibitor of CE, in nude mice with xenograft tumours. Initial experiments showed that the optimal dose of CPT-11 was 100 mg/kg. This dose was then used to study the anti-tumour effects of CPT-11 with and without BNPP. A direct correlation was found between the dose of administered BNPP and the growth rate of the tumour, demonstrating that the anti-tumour effects of CPT-11 were related to the CE concentration. Measuring the concentration of CE may allow the optimum dose of CPT-11 to be determined, opening up the possibility of individualized chemotherapy programmes.

scholarly journals Prevention of Colon Cancer Recurrence From Minimal Residual Disease: Computer Optimized Dose Schedules of Intermittent Apoptotic Adjuvant Therapy

2020 ◽  
pp. 514-520
Author(s):  
Chase Cockrell ◽  
Joseph Teague ◽  
David E. Axelrod
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Adverse Effects ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Dose Intensity ◽  
Optimal Dose ◽  
Cytotoxic Agents ◽  
Optimum Dose ◽  
Minimal Residual

PURPOSE Adjuvant chemotherapy is used after surgery for stages II and III colorectal cancer to reduce recurrence. Nevertheless, recurrence may occur years later with the emergence of initially undetected minimal residual disease (MRD). Attempts to reduce recurrence by increasing the dose intensity and increasing the time of adjuvant therapy have been limited by the adverse effects of the recommended cytotoxic agents. The goals of this study were to suggest an alternative to the recommended cytotoxic agents and to determine optimal adjuvant therapy dose schedules that would reduce the percentage of recurrence at 5 years while retaining colon crypt function. METHODS A total of 84,400 dose schedules with different duration, interval between doses, and intensity of treatment were simulated with a high-performance computer. Simulated treatments used the drug sulindac, which had previously been used in primary prevention. With appropriate dose schedules, it can induce apoptosis at the crypt lumen surface while retaining crypt function. We used a computer model of cell dynamics in colon crypts that had been calibrated with measurements of human biopsy specimens. Proliferating mutant cells were assumed to emerge from MRD within crypts. Simulated outcomes included the recurrence percentage at 5 years and the retention of crypt function. RESULTS Optimal dose schedules were determined for adjuvant treatment of MRD that reduced the percentage of recurrence at 5 years of stages I, II, and III colon cancer to zero. CONCLUSION A new adjuvant therapy for colon cancer based upon optimum dose schedules of intermittent apoptotic treatment may prevent the recurrence of colon cancer from MRD and avoid the adverse effects of cytotoxic treatments.

A Note on the Publication History of John Polidori's The Vampyre

2020 ◽  
Vol 22 (3) ◽  
pp. 330-343
Author(s):  
Fabio Camilletti
Keyword(s):  
Textual Criticism ◽  
Active Role ◽  
Publication History ◽  
History Of ◽  
The Relationship ◽  
Opening Up

It is generally assumed that The Vampyre was published against John Polidori's will. This article brings evidence to support that he played, in fact, an active role in the publication of his tale, perhaps as a response to Frankenstein. In particular, by making use of the tools of textual criticism, it demonstrates how the ‘Extract of a Letter from Geneva’ accompanying The Vampyre in The New Monthly Magazine and in volume editions could not be written without having access to Polidori's Diary. Furthermore, it hypothesizes that the composition of The Vampyre, traditionally located in Geneva in the course of summer 1816, can be postdated to 1818, opening up new possibilities for reading the tale in the context of the relationship between Polidori, Byron, and the Shelleys.

Researching (with) Major Food Retailers

2015 ◽  
Vol 15 (3) ◽  
pp. 33-39 ◽  
Author(s):  
David Evans
Keyword(s):  
Food Systems ◽  
Academic Research ◽  
Social Scientists ◽  
Major Food ◽  
Food Retailers ◽  
Food Retailer ◽  
The One ◽  
The Uk ◽  
The Relationship ◽  
Opening Up

This paper considers the relationship between social science and the food industry, and it suggests that collaboration can be intellectually productive and morally rewarding. It explores the middle ground that exists between paid consultancy models of collaboration on the one hand and a principled stance of nonengagement on the other. Drawing on recent experiences of researching with a major food retailer in the UK, I discuss the ways in which collaborating with retailers can open up opportunities for accessing data that might not otherwise be available to social scientists. Additionally, I put forward the argument that researchers with an interest in the sustainability—ecological or otherwise—of food systems, especially those of a critical persuasion, ought to be empirically engaging with food businesses. I suggest that this is important in terms of generating better understandings of the objectionable arrangements that they seek to critique, and in terms of opening up conduits through which to affect positive changes. Cutting across these points is the claim that while resistance to commercial engagement might be misguided, it is nevertheless important to acknowledge the power-geometries of collaboration and to find ways of leveling and/or leveraging them. To conclude, I suggest that universities have an important institutional role to play in defining the terms of engagement as well as maintaining the boundaries between scholarship and consultancy—a line that can otherwise become quite fuzzy when the worlds of commerce and academic research collide.

Predictive Failure Analysis of Solder Joints with Simultaneous High Speed EBSD and EDS

2018 ◽  
Author(s):  
J. Lindsay ◽  
P. Trimby ◽  
J. Goulden ◽  
S. McCracken ◽  
R. Andrews
Keyword(s):  
High Speed ◽  
Solder Joints ◽  
Phase Distribution ◽  
Bond Failure ◽  
Microstructural Parameters ◽  
Snpb Solder ◽  
Grain Orientations ◽  
Accelerated Thermal Cycling ◽  
The Relationship ◽  
Opening Up

Abstract The results presented here show how high-speed simultaneous EBSD and EDS can be used to characterize the essential microstructural parameters in SnPb solder joints with high resolution and precision. Analyses of both intact and failed solder joints have been carried out. Regions of strain localization that are not apparent from the Sn and Pb phase distribution are identified in the intact bond, providing key insights into the mechanism of potential bond failure. In addition, EBSD provides a wealth of quantitative detail such as the relationship between parent Sn grain orientations and Pb coarsening, the morphology and distribution of IMCs on a sub-micron scale and accurate grain size information for all phases within the joint. Such analyses enable a better understanding of the microstructural developments leading up to failure, opening up the possibility of improved accelerated thermal cycling (ATC) testing and better quality control.

Lentiviral-Mediated Beclin-1 Overexpression Inhibits Cell Proliferation and Induces Autophagy of Human Esophageal Carcinoma Eca109 Cell Xenograft in Nude Mice

2020 ◽  
Vol 15 (1) ◽  
pp. 70-77
Author(s):  
Junhe Zhang ◽  
Weihua Dong
Keyword(s):  
Growth Rate ◽  
Cell Proliferation ◽  
Esophageal Carcinoma ◽  
Nude Mice ◽  
Beclin 1 ◽  
Control Group ◽  
Vector Group ◽  
Empty Vector ◽  
Empty Vector Group

Background: Esophageal carcinoma is one of the common malignant tumors in digestive tract. BECLIN-1 is a key gene that regulates autophagy, and its abnormal expression may be related with many human tumors. However, the mechanism of BECLIN-1 in esophageal carcinoma remains unknown. Objective: In this study, we explored the effect of BECLIN-1 overexpression on tumor growth in mice with esophageal carcinoma and its mechanism. Methods: Recombined lentiviral vector containing BECLIN-1 was used to transfect human esophageal carcinoma Eca109 cells and establish stable cell line. qRT-PCR was used to detect BECLIN-1 mRNA level in the transfected Eca109 cells, CCK-8 assay was used to detect cell proliferation. Beclin-1, P62 and LC3-II protein expression levels in Eca109 cells were detected using Western blot analysis. Subcutaneous xenograft nude mice model of human esophageal carcinoma was established, and the tumor growths in Beclin-1 group, control group and empty vector group were monitored. Beclin-1 protein expression in vivo was detected by immunohistochemistry. Results: Beclin-1 mRNA and protein were overexpressed in Eca109 cells. Compared with empty vector group, the growth rate of cells transfected with BECLIN-1 decreased significantly. Compared with the control group and empty vector group, the expression level of P62 protein in beclin-1 group was significantly decreased, while the expression level of LC3-II protein was significantly increased. The tumor growth rate in nude mice of Beclin-1 group was significantly lower than that of the control group and empty vector group, and Beclin-1 protein was mainly expressed in Beclin-1 group in vivo. Conclusion: BECLIN-1 can induce autophagy in esophageal carcinoma Eca109 cells, and it can significantly inhibit the growth of esophageal carcinoma.

scholarly journals Autophagy Modulators in Cancer Therapy

2021 ◽  
Vol 22 (11) ◽  
pp. 5804
Author(s):  
Kamila Buzun ◽  
Agnieszka Gornowicz ◽  
Roman Lesyk ◽  
Krzysztof Bielawski ◽  
Anna Bielawska
Keyword(s):  
Cancer Research ◽  
Cancer Therapy ◽  
Adverse Effects ◽  
Nutrient Deficiency ◽  
Molecular Regulation ◽  
Regulatory Pathways ◽  
Selective Autophagy ◽  
Atg Proteins ◽  
Different Types ◽  
The Relationship

Autophagy is a process of self-degradation that plays an important role in removing damaged proteins, organelles or cellular fragments from the cell. Under stressful conditions such as hypoxia, nutrient deficiency or chemotherapy, this process can also become the strategy for cell survival. Autophagy can be nonselective or selective in removing specific organelles, ribosomes, and protein aggregates, although the complete mechanisms that regulate aspects of selective autophagy are not fully understood. This review summarizes the most recent research into understanding the different types and mechanisms of autophagy. The relationship between apoptosis and autophagy on the level of molecular regulation of the expression of selected proteins such as p53, Bcl-2/Beclin 1, p62, Atg proteins, and caspases was discussed. Intensive studies have revealed a whole range of novel compounds with an anticancer activity that inhibit or activate regulatory pathways involved in autophagy. We focused on the presentation of compounds strongly affecting the autophagy process, with particular emphasis on those that are undergoing clinical and preclinical cancer research. Moreover, the target points, adverse effects and therapeutic schemes of autophagy inhibitors and activators are presented.

Dementia associated with epilepsy

2005 ◽  
Vol 17 (s1) ◽  
pp. S195-S206 ◽  
Author(s):  
Paulo Caramelli ◽  
Luiz Henrique Martins Castro
Keyword(s):  
Adverse Effects ◽  
Elderly Patients ◽  
Treatment Guidelines ◽  
Hippocampal Sclerosis ◽  
Mesial Temporal Lobe Epilepsy ◽  
Mesial Temporal Lobe ◽  
Impaired Cognition ◽  
Biological Abnormality ◽  
Available Information ◽  
The Relationship

In this review, we explore the relationship between epilepsy and cognition and between epilepsy and dementia. Chronic epilepsy, particularly mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, may be associated with impaired cognition, which can be secondary to uncontrolled seizures, to adverse effects of antiepileptic drugs (AEDs) or to the underlying biological abnormality. The choice of an adequate AED with an appropriate dose regimen may lead to a favorable outcome. This feature is especially relevant in elderly patients with dementia and associated epilepsy, a vulnerable population in which the diagnosis of seizures can be difficult and for whom treatment guidelines are not yet available. Based on available information and on data derived from studies with other populations, recommendations for the management of these patients are presented.

scholarly journals Effect of genotype, age of hens and K/k allele on eggshell quality

2011 ◽  
Vol 56 (No. 5) ◽  
pp. 242-249 ◽  
Author(s):  
Z. Ledvinka ◽  
L. Zita ◽  
M. Hubený ◽  
E. Tůmová ◽  
M. Tyller ◽  
...  
Keyword(s):  
Growth Rate ◽  
Egg Production ◽  
Statistical Significance ◽  
Live Weight ◽  
Shape Index ◽  
Feed Mixture ◽  
Eggshell Quality ◽  
Feather Growth ◽  
Two Factors ◽  
The Relationship

We assessed the influence of the particular genotype, age of layers, feather growth-rate gene, and their mutual interactions on selected indicators of eggshell quality in six groups of hens of the laying type Dominant. The following genotypes were examined in the experiment: Barred Plymouth Rock, Dominant BPR 951 (K) strain, slow-feathering; Barred Plymouth Rock, Dominant BPR 901 (k) strain, fast-feathering; Blue Plymouth Rock, Dominant BLPR 954 (K) strain, slow-feathering; Blue Plymouth Rock, Dominant BLPR 894 (k) strain, fast-feathering; crossbreds of the above strains in the F<sub>1</sub> generation Dominant D 107 blue (K), slow-feathering and Dominant D 107 blue (k), fast-feathering. The layers were fed a feed mixture NP1 (16.64 % CP) from the 20<sup>th</sup> week of age and a feed mixture NP2 (15.02% CP) from the 42<sup>nd</sup> week. Husbandry conditions met the regular requirements of laying hens. Egg production and live weight of hens were monitored for the duration of the experiment (12 months). Eggshell quality was examined at the layers' age of 27, 35 and 56 weeks. The average hen-day egg production for the duration of the experiment (12 months) was not significantly influenced by the particular genotype or the feather growth-rate gene. The varying representation of the feather growth-rate gene significantly (P &le; 0.001) influenced the live weight; similarly, the relationship between the genotype and the representation of K/k alleles was significant. The average egg weight was influenced statistically significantly (P &le; 0.001) by the age of hens, their genotype (P &le; 0.05), feather growth-rate gene (P &le; 0.001), and the relationship between the age and genotype (P &le; 0.001). The age of hens, genotype, and the interaction of these two factors affected the egg shape index, as did the incidence of the feather growth-rate gene within the population (with a statistical significance of P &le; 0.001). The age, genotype and the feather growth-rate gene incidence within the population also significantly affected the eggshell quality indicators. In the eggshell to egg ratio, eggshell thickness and strength, an interaction was determined between the age of hens and their particular genotype. The eggshell colour was also significantly (P &le; 0.001) affected by hens' age, genotype (P &le; 0.001), as well as by the feather growth-rate gene (P &le; 0.001). No significant interaction between the age and the genotype was found for this indicator.

Climate change in the Cameroonian press: An analysis of its representations

2020 ◽  
pp. 096366252097601
Author(s):  
Nicole Kay ◽  
Sandrine Gaymard
Keyword(s):  
Climate Change ◽  
Media Coverage ◽  
Psychological Distance ◽  
Environmental Issue ◽  
Social Psychological ◽  
Global Environmental Issue ◽  
Global Environmental ◽  
The World ◽  
The Relationship ◽  
Opening Up

Climate change is a global environmental issue and its outcome will affect societies around the world. In recent years, we have seen a growing literature on media coverage of climate change, but, to date, no study has assessed the situation in Cameroon, although it is considered to be one of the world’s most affected and vulnerable regions. This study attempted to address this deficit by analysing how climate change is represented in the Cameroonian media. A similarity analysis was performed on three newspapers published in 2013–2016. Results showed that climate coverage focused on politics and international involvement. It seems disconnected from local realities, potentially opening up a spatial and social psychological distance. The relationship between the representation of climate change and that of poverty is an area for further exploration.

A NOTE ON INFLATION, ECONOMIC GROWTH, AND INCOME INEQUALITY

2009 ◽  
Vol 13 (1) ◽  
pp. 138-147 ◽  
Author(s):  
Yi Jin
Keyword(s):  
Economic Growth ◽  
Growth Rate ◽  
Income Inequality ◽  
Endogenous Growth ◽  
Money Growth ◽  
Relative Importance ◽  
Long Run ◽  
Endogenous Growth Model ◽  
The Relationship ◽  
Negative Growth

This paper develops a monetary endogenous growth model with capital and skill heterogeneity to analyze the relationship among inflation, growth, and income inequality. In the model inflation, growth, and inequality are jointly determined. We show that an increase in the long-run money growth rate raises inflation and reduces growth, but its effect on income inequality depends on the relative importance of the two types of heterogeneity. Inequality shrinks with the rise of inflation when capital heterogeneity dominates and enlarges when skill heterogeneity dominates. Therefore, our model supports a negative (positive) inflation–inequality relationship and a positive (negative) growth–inequality relationship when capital (skill) heterogeneity dominates. In any event, inflation and growth are negatively related.

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