107 research outputs found
Treatment Options in Metastatic Renal Cell Carcinoma: Focus on mTOR Inhibitors
The agents currently approved for use in metastatic renal cell carcinoma (mRCC) can be divided broadly into two categories: (1) vascular endothelial growth factor receptor (VEGFR)-directed therapies or (2) inhibitors of the mammalian target of rapamycin (mTOR). The latter category includes everolimus and temsirolimus, both approved for distinct indications in mRCC. Everolimus gained its approval on the basis of phase III data showing a benefit in progression-free survival relative to placebo in patients previously treated with sunitinib and/or sorafenib. In contrast, temsirolimus was approved on the basis of a phase III trial in treatment-naïve patients with poor-risk mRCC, demonstrating an improvement in overall survival relative to interferon-alfa. While these pivotal trials have created unique positions for everolimus and temsirolimus in current clinical algorithms, the role of mTOR inhibitors in mRCC is being steadily revised and expanded through ongoing trials testing novel sequences and combinations. The clinical development of mTOR inhibitors is outlined herein
Critical appraisal of cabazitaxel in the management of advanced prostate cancer
Docetaxel remains a cornerstone of therapy for the patient with metastatic castration-resistant prostate cancer (CRPC). However, the landscape of CRPC therapy is changing rapidly – recently, data from the phase III TROPIC study revealed a survival advantage with the novel taxane cabazitaxel/prednisone (compared with mitoxantrone/prednisone) in a cohort of 755 men with docetaxel-refractory metastatic CRPC. Interestingly, cabazitaxel bears substantial structural similiarity to docetaxel but appears to be mechanistically distinct. In preclinical studies, the agent has antitumor activity in a variety of docetaxel-refractory in vitro and in vivo models. Subsequent to phase I testing in advanced solid tumors (where neutropenia was identified as a dose-limiting toxicity), the agent was assessed in a phase II trial in advanced, taxane-refractory breast cancer and in the aforementioned phase III TROPIC study. This review describes in detail the preclinical and clinical development of cabazitaxel
COVID-19 and financial toxicity in patients with renal cell carcinoma
PURPOSE To ascertain renal cell carcinoma (RCC) financial toxicity on COVID-19 during the COVID-19 crisis as patients are struggling with therapeutic and financial implications. METHODS An online survey was conducted from March 22 to March 25, 2020. It included baseline demographic, clinicopathologic, treatment-related information, anxiety levels related to COVID-19, questions related to financial concerns about COVID-19 as well as the validated 11-item COST measure. RESULTS Five-hundred-and-thirty-nine patients (39%:58% male:female) from 14 countries responded. 23% of the patients did not feel in control of their financial situation but 8% reported being very satisfied with their finances. The median COST score was 21.5 (range 1-44). Metastatic patients who have not started systemic therapy had a COST score (19.8 range 2-41) versus patients on oral systemic therapy had a COST score (23.9 range 4-44). Patients in follow-up after surgery had a median COST score at 20.8 (range 1-40). A low COST scores correlated (p < 0.001) were female gender (r = 0.108), younger age (r = 0.210), urban living situation (r = 0.68), a lower educational level (r = 0.155), lower income (r = 0.165), higher anxiety about acquiring COVID-19 (r = 0.198), having metastatic disease (r = 0.073) and a higher distress score about cancer progression (r = 0.224). CONCLUSION Our data highlight severe financial impact of COVID-19. Acknowledging financial hardship and thorough counseling of cancer patients should be part of the conversation during the pandemic. Treatment and surveillance of RCC patients might have to be adjusted to contemplate financial and medical needs
Оценивание финансово-экономической безопасности предприятий молокоперерабатывающей отрасли
The essence of the concept “financial and economic security of the enterprise” is
covered. Methodological approaches to the enterprise financial and economic security evaluation
are considered, enabling the method of index numberrating score of the enterprise financial and
economic security to be found. Dynamics of milk anddairy production in Ukraine has been studied.
Ukrainian regions leading in liquid processed milk production have been identified. Dynamics of
milk and dairy production per man has been analyzed which allowed to find out the annual
increase in demand per man. Integrated index of the dairy enterprise financial and economic
security has been evaluated. As a result, the ways to increase the managerial efficiency of financial
and economic security of the following enterprises:PJSC "Dubnomoloko", PJSC "Kupyans'ki milk
canning plant", PJSC the "Yagotyns'ki creamery", PJSC the "Pervomais'ki milk canning plant" are
offered.У статті розкрито сутність поняття фінансово-економічної безпеки
підприємства. Розглянуто методичні підходи щодо оцінювання фінансово-економічної
безпеки підприємства, що дозволило виявити підхід рейтингової оцінки показника
фінансово-економічної безпеки підприємства. Досліджено динаміку виробництва молока та
молочних продуктів України. Виявити області України, які є лідерами з виробництва молока
рідкого обробленого. Проаналізовано динаміку виробництва молока та молочних продуктів
на одну особу, що дозволило встановити щорічне зростання попиту на одну особу.
Визначено підприємства молокопереробної галузі. Проведено оцінку інтегрального
показника фінансово-економічної безпеки підприємств молокопереробної галузі. За
результатами оцінки запропоновано шляхи підвищення ефективності управління фінансово-економічної безпеки таких підприємств, як: ПАТ «Дубномолоко», ПАТ «Куп’янський
молочноконсервний комбінат», ПАТ «Яготинський маслозавод», ПАТ «Первомайський
молочноконсервний комбінат».В статье раскрыто сущность понятия финансово-экономическая
безопасность предприятия. Рассмотрено методические подходы относительно оценивания
финансово-экономической безопасности предприятия, что позволило выявить поход
рейтинговой оценки показателя финансово-экономической безопасности предприятия.
Исследовано динамику производства молока и молочных продуктов Украины. Выявлены
области Украины, которые являются лидерами по производству молока жидкого
обработанного. Проанализировано динамику производства молока и молочных продуктов на
одного человека, что позволило установить ежегодный рост спроса на одного человека.
Определены предприятия молокоперерабатывающей отрасли. Проведена оценка
интегрального показателя финансово-экономической безопасности предприятий
молокоперерабатывающей отрасли. По результатам оценки предложены пути повышения
эффективности управления финансово-экономической безопасности таких предприятий,
как: ПАО «Дубномолоко», ПАО «Купянский молочноконсервный комбинат», ПАО
«Яготинский маслозавод», ПАО «Первомайский молочноконсервный комбинат»
Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)
The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the
India-based Neutrino Observatory (INO) is designed to study the atmospheric
neutrinos and antineutrinos separately over a wide range of energies and path
lengths. The primary focus of this experiment is to explore the Earth matter
effects by observing the energy and zenith angle dependence of the atmospheric
neutrinos in the multi-GeV range. This study will be crucial to address some of
the outstanding issues in neutrino oscillation physics, including the
fundamental issue of neutrino mass hierarchy. In this document, we present the
physics potential of the detector as obtained from realistic detector
simulations. We describe the simulation framework, the neutrino interactions in
the detector, and the expected response of the detector to particles traversing
it. The ICAL detector can determine the energy and direction of the muons to a
high precision, and in addition, its sensitivity to multi-GeV hadrons increases
its physics reach substantially. Its charge identification capability, and
hence its ability to distinguish neutrinos from antineutrinos, makes it an
efficient detector for determining the neutrino mass hierarchy. In this report,
we outline the analyses carried out for the determination of neutrino mass
hierarchy and precision measurements of atmospheric neutrino mixing parameters
at ICAL, and give the expected physics reach of the detector with 10 years of
runtime. We also explore the potential of ICAL for probing new physics
scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration,
Contents identical with the version published in Pramana - J. Physic
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
A Proposal for an Electrostatic Doping-Assisted Electroabsorption Modulator for Intrachip Communication
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