scholarly journals STEM-24. RADIATION-INDUCED EXTRACELLULAR VESICLE (EV) RELEASE OF miR-603 PROMOTES IGF1-MEDIATED STEM CALL STATE IN GLIOBLASTOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii201-ii201
Author(s):  
Valya Ramakrishnan ◽  
Beibei Xu ◽  
Johnny Akers ◽  
Thien Nguyen ◽  
Jun Ma ◽  
...  
Keyword(s):  
Recipient Cell ◽  
Alkylating Agents ◽  
Acquired Resistance ◽  
Standard Of Care ◽  
Extracellular Vesicle ◽  
Cross Resistance ◽  
Dna Damages ◽  
Care Treatment ◽  
Standard Of Care Treatment ◽  
The Impact

Abstract INTRODUCTION Release of exosomes and extracellular vesicles (EV) by glioblastomas plays key roles in modulating the tumor microenvironment and therapeutic response. Studies to date have largely focused on the impact of EV and exosomes on the recipient cell. Here, we demonstrate that EV-mediated export of a master-regulatory miRNA has fate-determining impacts on the cell releasing the EVs. METHODS microRNA (miRNA) profiling was performed using clinical glioblastoma specimens from the same patients derived pre- and post-standard of care treatment. Mechanism mediating altered miRNA homeostasis were assessed. RESULTS While the levels of nearly all miRNAs remained unchanged after standard-of-care treatment, decreased levels of few, select miRNAs were observed, including miR-603. In response to ionizing radiation (IR), but not temozolomide (TMZ), glioblastoma cell lines exhibited a time-dependent decrease in miR-603 levels. While miR-603 biogenesis and degradation remained unchanged after IR, IR induced an increase in EV-mediated export of miR-603. Profiling of miR-603 targets revealed that miR-603 repressed the insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), genes required to maintain the cancer stem cell (CSC) state, as well as MGMT, the gene encoding a DNA repair protein that detoxifies temozolomide (TMZ) induced DNA damages. IR induced export of miR-603 de-repress IGF1/IGF1R to promote radiation resistance and de-repress MGMT to promote cross-resistance to TMZ and CCNU. Ectopic miR-603 expression overwhelmed cellular capacity for miR-603 export and synergized with the tumoricidal effects of IR and temozolomide (TMZ). CONCLUSIONS Radiation stimulated EV-mediated export of miR-603 to facilitate acquired resistance to IR and cross-resistance to DNA alkylating agents.

scholarly journals Under-Treatment of Older Patients with Newly Diagnosed Epithelial Ovarian Cancer Remains an Issue

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 952
Author(s):  
Lucy Dumas ◽  
Rebecca Bowen ◽  
John Butler ◽  
Susana Banerjee
Keyword(s):  
Ovarian Cancer ◽  
Older Women ◽  
Older Patients ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Standard Of Care ◽  
First Line ◽  
Care Treatment ◽  
Platinum Based Chemotherapy ◽  
Standard Of Care Treatment

Older women with ovarian cancer have disproportionately poorer survival outcomes than their younger counterparts and receive less treatment. In order to understand where the gaps lie in the treatment of older patients, studies incorporating more detailed assessment of baseline characteristics and treatment delivery beyond the scope of most cancer registries are required. We aimed to assess the proportion of women over the age of 65 who are offered and receive standard of care for first-line ovarian cancer at two UK NHS Cancer Centres over a 5-year period (December 2009 to August 2015). Standard of care treatment was defined as a combination of cytoreductive surgery and if indicated platinum-based chemotherapy (combination or single-agent). Sixty-five percent of patients aged 65 and above received standard of care treatment. Increasing age was associated with lower rates of receiving standard of care (35% > 80 years old versus 78% of 65–69-year-olds, p = 0.000). Older women were less likely to complete the planned chemotherapy course (p = 0.034). The oldest women continue to receive lower rates of standard care compared to younger women. Once adjusted for Federation of Gynaecology and Obstetrics (FIGO) stage, Eastern Cooperative Oncology Group (ECOG) performance status and first-line treatment received, age was no longer an independent risk factor for poorer overall survival. Optimisation of vulnerable patients utilising a comprehensive geriatric assessment and directed interventions to facilitate the delivery of standard of care treatment could help narrow the survival discrepancy between the oldest patients and their younger counterparts.

Do elderly women with endometrial cancer receive standard of care treatment?

2021 ◽  
Vol 162 ◽  
pp. S139
Author(s):  
Michelle Soloff ◽  
Aaron Nizam ◽  
Ariel Kredentser ◽  
Bethany Bustamante ◽  
Weiwei Shan ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Elderly Women ◽  
Standard Of Care ◽  
Care Treatment ◽  
Standard Of Care Treatment

scholarly journals Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non–Small Cell Lung Cancer

JAMA Oncology ◽  
2018 ◽  
Vol 4 (12) ◽  
pp. e183486 ◽  
Author(s):  
Cesare Gridelli ◽  
Javier de Castro Carpeno ◽  
Anne-Marie C. Dingemans ◽  
Frank Griesinger ◽  
Francesco Grossi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Standard Of Care ◽  
Small Cell ◽  
Small Cell Lung ◽  
Safety And Efficacy ◽  
Care Treatment ◽  
Standard Of Care Treatment

scholarly journals Myoclonic jerks complicating treatment of acute promyelocytic leukemia: case report and literature review

2019 ◽  
Vol 3 (12) ◽  
pp. 1854-1857 ◽  
Author(s):  
John Y. Rhee ◽  
Douglas Tremblay ◽  
Amy M. Chan ◽  
Martin S. Tallman ◽  
John Mascarenhas
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Acute Promyelocytic Leukemia ◽  
Standard Of Care ◽  
Promyelocytic Leukemia ◽  
Low Risk ◽  
Neurologic Complications ◽  
Care Treatment ◽  
Key Points ◽  
Standard Of Care Treatment

Key Points Myoclonic jerks and inattentiveness may be rare neurologic complications of ATO toxicity. Clinicians must be aware of this rare toxicity given that the ATO and ATRA combination is now standard-of-care treatment of low-risk APL.

Use of placebo in cancer medicine: The experience of a National Clinical Trials organization

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6104-6104
Author(s):  
J. L. Pater ◽  
W. Parulekar
Keyword(s):  
Clinical Trials ◽  
Supportive Care ◽  
Study Design ◽  
Standard Of Care ◽  
Phase Iii ◽  
Design Data ◽  
Standard Of Care Treatment ◽  
Prevention Trials ◽  
The Impact ◽  
Phase Iii Studies

6104 Background: The use of placebos in cancer clinical trials requires careful evaluation. Factors that must be considered include the impact of placebo on endpoint measurement, the efficacy of placebo relative to standard of care treatment, patient altruism/acceptance of a non-active intervention and the resulting increase in complexity of study conduct with respect to randomization, drug supply, data management, analysis and the unblinding process. Methods: We reviewed the experience of the National Cancer Institute of Canada Clinical Trials Group with the use of placebo in the randomized phase III setting from 1982–2005. Results: Since 1982, 34 studies were identified that utilized a placebo as part of study design. Data is presented below according to the type of study and date of study activation. The numbers in brackets represent those studies in which placebo was used alone in the control arm. Supportive care studies were the most common type of study employing a placebo as part of study design and constituted almost 50% of our Group’s experience. Therapeutic studies involving placebo were conducted in multiple sites including breast (4), lung (6), myeloma (1), melanoma (1), ovary (1) and pancreas (1). Conclusion: Phase III studies involving a placebo constitute an important part of our clinical trial activity and cross the spectrum of supportive care, therapeutic and prevention trials. The use of placebo in cancer studies may increase due to the relative ease of blinding in studies that evaluate targeted, oral therapies with minimal toxicities as well as the need for unbiased assessment of increasingly used endpoints such as time to progression. [Table: see text] No significant financial relationships to disclose.

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