line standard
Recently Published Documents


TOTAL DOCUMENTS

63
(FIVE YEARS 24)

H-INDEX

8
(FIVE YEARS 3)

2021 ◽  
Vol 23 (1) ◽  
pp. 157
Author(s):  
Kai Zhao ◽  
Agnes Schäfer ◽  
Zhuo Zhang ◽  
Katharina Elsässer ◽  
Carsten Culmsee ◽  
...  

About 95% of Glioblastoma (GBM) patients experience tumor relapse as a consequence of resistance to the first-line standard chemotherapy using temozolomide (TMZ). Recent studies reported consistently elevated expression levels of carbonic anhydrase CA2 in recurrent glioblastoma and temozolomide-resistant glioblastoma stem-like cells (GSCs). Here we show that CA2 is preferentially expressed in GSCs and upregulated by TMZ treatment. When expressed in GBM cell lines, CA2 exerts significant metabolic changes reflected by enhanced oxygen consumption and increased extracellular acidification causing higher rates of cell invasion. Notably, GBM cells expressing CA2 respond to combined treatment with TMZ and brinzolamide (BRZ), a non-toxic and potent CA2 inhibitor. Interestingly, brinzolamide was more effective than the pan-CA inhibitor Acetazolamide (ACZ) to sensitize naïve GSCs and TMZ-resistant GSCs to TMZ induced cell death. Mechanistically, we demonstrated that the combined treatment of GBM stem cells with TMZ and BRZ caused autophagy of GBM cell lines and GSCs, reflected by enhanced LC3 cleavage (LC3-II) and p62 reduction. Our findings illustrate the potential of CA2 as a chemo-sensitizing drug target in recurrent GBM and propose a combined treatment of TMZ with CA2 inhibitor to tackle GBM chemoresistance and recurrence.


2021 ◽  
Vol 21 (5) ◽  
pp. 369-378
Author(s):  
Hyunji Koo ◽  
Martin Salter ◽  
No-Weon Kang ◽  
Nick Ridler ◽  
Young-Pyo Hong

This paper evaluates the uncertainty of S-parameter measurements on multilayer printed circuit boards (PCBs) due to the uncertainties of the dimensions and dielectric properties of the line standard in the Thru-Reflect-Line (TRL) calibration. This evaluation is performed in two ways: one is based on repeated TRL calibrations with a randomly perturbed line standard, and the other is based on equations given by Stumper. The two methods require the uncertainties of the S-parameters of the TRL line standard, which are obtained from the uncertainties of the dimensions and dielectric properties using three-dimensional electromagnetic Monte Carlo simulation. The two methods agree well with each other. This study also shows how to apply impedance renormalization in Stumper’s equations. We design the TRL standards and the devices under test (DUTs) in PCB stripline and precisely measure the cross-sectional dimensions of the fabricated striplines. Uncertainty analysis based on the measured values enables us to investigate the impact of realistic deviations in the dimensions of the TRL line standard on the S-parameter measurement uncertainty of the DUTs. Finally, as an example, we evaluated the uncertainty in the measured S-parameters of a Beatty line on the fabricated PCB.


Author(s):  
Thorsten Fuereder

SummaryDuring the ASCO 2021 virtual meeting, multiple clinically relevant studies were presented addressing open questions regarding the therapy of nasopharyngeal carcinomas (NPC): Is immunotherapy plus chemotherapy the new first line standard of care for patients in the recurrent/metastatic setting? Is adjuvant therapy with capecitabine in high risk NPC patients post chemoradiation (CRT) beneficial? Is there a role for treatment intensification by adjuvant metronomic capecitabine in NPC patients post induction chemotherapy and CRT? This article summarizes the most significant NPC studies presented at the ASCO 2021 virtual meeting and discusses the data in the context of the current literature.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17510-e17510
Author(s):  
Lingying Wu ◽  
Xiumin Li ◽  
Jing Wang ◽  
Lijing Zhu ◽  
Ruifang An ◽  
...  

e17510 Background: Limited effective treatments are available for advanced cervical cancer patients who progress after first-line chemotherapy. Historic data indicate PD-1 antibodies have significant activity in advanced cervical cancer patients. This study was designed to determine the efficacy and safety of HLX10 (a recombinant humanized anti-PD-1 monoclonal antibody) plus albumin-bound paclitaxel in patients with advanced cervical cancer who have progressed on or are intolerant to first-line standard chemotherapy. Methods: This is an ongoing single-arm, open-label, multicenter, two-stage phase 2 study (NCT04150575). 143 eligible patients aged between 18 and 75, with histologically or cytologically diagnosed cervical cancer and positive PD-L1 expression (combined positive score [CPS] ≥1) were planned to be enrolled and given intravenous infusion of HLX10 (4.5 mg/kg) plus albumin-bound paclitaxel (260 mg/m2) every 3 weeks. Stage one (N = 20) was a safety run-in and preliminary efficacy exploration study with primary endpoints of adverse events, serious adverse events and objective response rate (ORR, assessed by IRRC per RECIST v1.1). In this stage, after all patients completed two tumor evaluations (every 6 weeks), a safety evaluation and a preliminary evaluation of anti-tumor efficacy were conducted to determine whether to proceed to the second stage (N = 123). Stage two is a single-arm, open-label, multicenter, phase 2 study with primary endpoint of ORR assessed by IRRC per RECIST v1.1. Results: Here we report the stage one results (safety and preliminary efficacy) of HLX10 in advanced cervical cancer patients. By cut-off date Oct 14, 2020, 21 eligible patients with median age of 50 (range: 31–65) and average CPS of 39.33 were enrolled; the median follow-up duration was 4.34 months. 71.4% patients had ECOG PS 1. The ORR assessed by IRRC and investigators were 52.4% (95% CI: 29.8%, 74.3%) and 42.9% (95% CI: 21.8%, 66.0%), respectively. The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were decreased neutrophil counts (n = 7, 33.3%), decreased white blood cell count (n = 6, 28.6%) and anemia (n = 4, 19.0%). No TEAEs leading to drug discontinuation were observed. One death (multiple organ dysfunction syndrome) possibly related to treatment was reported. Conclusions: Stage one results demonstrated a manageable safety profile and encouraging efficacy (ORR 52.4%) of HLX10 plus albumin-bound paclitaxel in advanced cervical cancer patients who have progressive disease or intolerable toxicity to first-line standard chemotherapy, representing a novel potential treatment option that warranted further investigation. Clinical trial information: NCT04150575.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 998
Author(s):  
Chiara Lazzari ◽  
Aurora Mirabile ◽  
Alessandra Bulotta ◽  
Maria Grazia Viganó ◽  
Francesca Rita Ogliari ◽  
...  

Several trials have tried for decades to improve the outcome of extensive disease small cell lung cancer (ED-SCLC) through attempts to modify the standard treatments. Nevertheless, platinum/etoposide combination and topotecan have remained respectively the first and the second line standard treatments for the last 40 years. With the advent of immunotherapy, this scenario has finally changed. Our review aims to provide an overview of the primary studies on the actual therapeutic strategies available for ED-SCLC patients, and to highlight emerging evidence supporting the use of immunotherapy in SCLC patients.


In light of human rights, poverty has multidimensional faces, so it is quite complicated to define the term poverty. Some scholars have argued that poverty is a cause and consequence of human rights violation, whereas, rest of others found that poverty itself is a violation of human rights. So it is not clear to what extent poverty violates human rights. This ambiguity leads to some other issues such, the exact definition of poverty, the approach of human rights, the link between discrimination and poverty, whether the poverty line standard maintains equity, the legal obligations of duty holders, and the human rights approach in incorporate in poverty-reducing plans. All through the world, there are various types of human rights discriminatory laws that exist and which lead to poverty. It can be said that State actions fail to reduce poverty owing to the absence or inadequacy of policies and programs and the lack of appropriate government expenses, in cases where resources are available. This paper is made with the purpose to clarify the term human rights and poverty. It is necessary to draw a link between human rights and poverty. This paper also has some other purposes, such as, try to find out reasons for poverty, giving importance to the duty bearer obligations, and designing the poverty reduction strategies under the human rights approach.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii212-ii213
Author(s):  
Lu Sun ◽  
Jenny Kienzler ◽  
Alexander Lee ◽  
Frances Chow ◽  
Carolina Chavez ◽  
...  

Abstract Brain metastases (BM) commonly arise in patients with melanoma, lung, and breast cancer. Currently, there are limited options for GBM and BM patients who have failed the first-line standard treatment, underscoring the importance of developing new therapeutic strategies. Last year, we and other groups evaluated the neoadjuvant timing of anti-PD-1 checkpoint blockade therapy in recurrent GBM (rGBM) patients, which resulted in a modest survival benefit. In light of the known effectiveness of anti-PD-1 as a systemic therapy to control melanoma and non-small cell lung cancer BM, we set out to study the anti-tumor immune response of BM patients to anti-PD-1 in the neoadjuvant setting. We posited that neoadjuvant anti-PD-1 in patients with BM would result in a stronger antitumoral immune response, which could be quantified at the single cell level. To test this, we made use of contemporary single cell techniques, including multiplex immunofluorescence, time-of-flight mass cytometry (CyTOF) and single-cell RNA sequencing (scRNAseq), to characterize the intratumoral immune cell populations and their transcriptomic profiles. We found that neoadjuvant anti-PD-1 significantly increased the number of tumor infiltrating T lymphocytes in BM compared to rGBM (2.5 fold in BM, p= 0.02 vs. 1.4 fold in rGBM, p= 0.19). Multiplex immunofluorescence analysis of T cells in BM samples revealed a change from T cell exclusion to a diffusely infiltrating phenotype after anti-PD-1 treatment. Importantly, BM showed a higher fraction of effector/cytotoxic T cells compared to rGBM (7.3% vs. 0.9% of lymphoid cells, p= 0.005) and anti-PD-1 further enhanced this population. In the myeloid compartment of BM, neoadjuvant anti-PD-1 increased the frequency of HLA-DR+CD206- M1-like macrophages, implicating a pro-inflammatory microenvironment. In summary, our study delineated the immune cell subtypes altered by neoadjuvant anti-PD-1 and offers insights into new combination therapies that can help understand the clinical efficacy of immunotherapy for BM and GBM patients.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4641-4641
Author(s):  
Andrew Eugene Hendifar ◽  
Edik Matthew Blais ◽  
Camille Ng ◽  
Dzung Thach ◽  
Jun Gong ◽  
...  

4641 Background: Approximately 90% of PDAC tumors are driven by activating KRAS mutations. The biological and clinical impact of common KRAS variants (e.g. G12D, G12V, G12R) and less common variants (e.g. G12C, Q61H, Q61R) remains largely unknown despite the emergence of variant-specific treatment strategies. Methods: We retrospectively analyzed real-world outcomes from 1475 PDAC pts who underwent molecular profiling via the Know Your Tumor program. Overall survival (OS) and progression-free survival (PFS) were analyzed by choice of 1st line standard therapies. Outcomes in pts with specific KRAS mutations were compared against the KRAS G12D cohort using Cox regression. Based on our prior data, tumor profiles with actionable molecular findings (DDR mutations or other drivers) were evaluated separately. Results: The prognostic/predictive value of specific KRAS variants revealed differences in real-world outcomes (Table). OS was greater in pts with KRAS G12V and G12R variants, as was PFS on 5FU-Based Therapy (e.g. FOLFIRINOX) but not for Gemcitabine/nab-Paclitaxel. Opposing trends were noted for KRAS Q61. Pts with KRAS wild type tumors as well as both actionable subgroups also had an improved OS. Conclusions: In this large national dataset, we demonstrate that KRAS mutation status and specific variants appear to be prognostic as well as predictive in pancreatic cancer. [Table: see text]


Sign in / Sign up

Export Citation Format

Share Document