Genetic alterations in HRAS gene in relation to outcome and response to cetuximab in head and neck squamous cell carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5574-5574
Author(s):  
Theodoros Rampias ◽  
Athina Giagini ◽  
Hiroumi Matsuzaki ◽  
Valentina Bartzi ◽  
Spyros Siolos ◽  
...  
Keyword(s):  
Cell Lines ◽  
Mapk Pathway ◽  
Small Sample Size ◽  
Mutant Cell ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Resistant Cell ◽  
Small Sample ◽  
The Impact ◽  
Hras Gene

5574 Background: Aberrant signaling through RAS/MAPK pathway is implicated in resistance to EGFR-targeted agents in cancer. Genetic alterations in Hras gene such as mutations and specific polymorphisms are associated with aggressive phenotype in several smoking-related malignancies. We sought to determine the impact of Hras genetic alterations on response to cetuximab and prognosis in HNSCC. Methods: Clinical outcome according to Hras status was investigated in a retrospective cohort of 140 HNSCC specimens. Primary endpoints were overall survival (OS) and disease-free survival (DFS) and secondary endpoint was treatment response. For statistical analysis, T-test was used for continuous data and x2 –test for categorical data. Cetuximab-resistant cell lines harboring mutant Hras (BB49, T24) were infected with lentivirus expressing shRNA targeting the Hras or a scrambled- shRNA. MTT assay was used to determine the effect of cetuximab on growth of lentivirus infected cells. Biochemical analysis involved immunoblotting for pERK1/2. Results: Mutationanalysis of tumor samples showed that 5.7% participants harbored Hras mutations and 16.42% harbored Hras polymorphisms (rs12628, rs41258054) that are associated with tumorigenesis. Patients bearing tumors with mutated Hras had inferior mean OS ( 22.13vs 35.20, p=0.02) and a non-significant trend for inferior mean DFS. Patients with tumors containing Hras genetic alterations (mutation or polymorphism) had significantly inferior mean OS (p=0.02) compared to those harboring wt Hras and trended towards inferior DFS (p=0.07). Patients had received various treatments such as surgery plus/minus RT and various chemotherapy regimens. A subgroup analysis of 38 patients treated with cetuximab-based regimens showed that wt Hras was associated with higher likelihood of attaining CR or PR to treatment of borderline significance (p=0.06) due to small sample size. Silencing of Hras in Hras-mutant cell lines restored sensitivity to cetuximab and caused a direct downregulation of pERK1/2 levels. Conclusions: Hras genetic alterations are associated with aggressive clinical course and may affect response to cetuximab in HNSCC.

scholarly journals Dissecting Mechanisms of Melanoma Resistance to BRAF and MEK Inhibitors Revealed Genetic and Non-Genetic Patient- and Drug-Specific Alterations and Remarkable Phenotypic Plasticity

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 142 ◽  
Author(s):  
Mariusz L. Hartman ◽  
Malgorzata Sztiller-Sikorska ◽  
Anna Gajos-Michniewicz ◽  
Malgorzata Czyz
Keyword(s):  
Phenotypic Plasticity ◽  
Cell Lines ◽  
Mapk Pathway ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Genetic Alterations ◽  
Resistant Cell ◽  
Cross Resistance ◽  
Preclinical Model ◽  
Development Of Resistance

The clinical benefit of MAPK pathway inhibition in BRAF-mutant melanoma patients is limited by the development of acquired resistance. Using drug-naïve cell lines derived from tumor specimens, we established a preclinical model of melanoma resistance to vemurafenib or trametinib to provide insight into resistance mechanisms. Dissecting the mechanisms accompanying the development of resistance, we have shown that (i) most of genetic and non-genetic alterations are triggered in a cell line- and/or drug-specific manner; (ii) several changes previously assigned to the development of resistance are induced as the immediate response to the extent measurable at the bulk levels; (iii) reprogramming observed in cross-resistance experiments and growth factor-dependence restricted by the drug presence indicate that phenotypic plasticity of melanoma cells largely contributes to the sustained resistance. Whole-exome sequencing revealed novel genetic alterations, including a frameshift variant of RBMX found exclusively in phospho-AKThigh resistant cell lines. There was no similar pattern of phenotypic alterations among eleven resistant cell lines, including expression/activity of crucial regulators, such as MITF, AXL, SOX, and NGFR, which suggests that patient-to-patient variability is richer and more nuanced than previously described. This diversity should be considered during the development of new strategies to circumvent the acquired resistance to targeted therapies.

Role of an extended pathology exam in risk classification of testicular germ cell tumors (GCTs).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15032-e15032
Author(s):  
Mihai Vasile Marinca ◽  
Irina Draga Caruntu ◽  
Ludmila Liliac ◽  
Simona Eliza Giusca ◽  
Andreea Marinca ◽  
...  
Keyword(s):  
Sample Size ◽  
Small Sample Size ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
Developed Countries ◽  
Small Sample ◽  
P Value ◽  
Testicular Germ Cell ◽  
Therapeutic Decisions ◽  
The Impact

e15032 Background: The 1997 IGCCCG Consensus classification provides clinicians with enough information to efficiently choose between treatment options for most GCT patients. Nevertheless, therapy is ineffective in 5-10% of cases (even more in less developed countries), and about the same numbers experience severe side effects. This exploratory study aims to assess the impact of more rigorous and detailed pathology examination on improving the assignation of these patients to prognostic groups and, consequently, making optimal therapeutic decisions. Methods: Predefined features were reviewed on histology slides from 39 GCT patients followed-up for a median of 48.28 months. We designed a uniform pathology protocol, focused on identifying potential new prognostic factors. Categorical and continuous variables were quantified using light microscopy and computer-aided morphometry and, due to the small sample size, their statistical correlation was analyzed by exact tests and Spearman’s rho, respectively. Significant (2-sided p-value <0.05, under sample size reserve) coefficient values were entered in hierarchical cluster analysis (HCA). Results: Favorable IGCCCG group, presence of seminoma, glandular tissue pattern, presence and histoarchitecture of lymphocytic infiltrate associated better survival rates and lower risk of progression. Invasion of the epididymis and spermatic cord, presence of teratoma, choriocarcinoma and yolk-sac elements, papillary pattern and cell pleomorphism predicted poorer outcomes. HCA yielded 2 significantly distinct patient groups in terms of overall survival (p=0.018) and time to progression (p=0.080), but not disease-free survival (p=0.614). Conclusions: Quantification of tumor subtypes and other histology features of GCTs (e.g. necrosis, tissue patterns, inflammation) is feasible and, if standardized, may prove useful in optimal selection of risk groups, when performed by an experienced pathologist.

An influence of social isolation on the level of physical activity as well as on well-being and mental state of people during the coronavirus COVID-19 pandemic

2019 ◽  
Vol 129 (4) ◽  
pp. 127-131
Author(s):  
Agnieszka Parfin ◽  
Krystian Wdowiak ◽  
Marzena Furtak-Niczyporuk ◽  
Jolanta Herda
Keyword(s):  
Physical Activity ◽  
Social Isolation ◽  
Small Sample Size ◽  
Statistical Tests ◽  
Population Group ◽  
Well Being ◽  
Small Sample ◽  
Subjective Well Being ◽  
Tract Infections ◽  
The Impact

AbstractIntroduction. The COVID-19 is the name of an infectious disease caused by a new strain of coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). It was first diagnosed in December 2019 in patients in Wuhan City, Hubei Province, China. The symptoms are dominated by features of respiratory tract infections, in some patients with a very severe course leading to respiratory failure and, in extreme cases to death. Due to the spread of the infection worldwide, the WHO declared a pandemic in March 2020.Aim. An investigation of the impact of social isolation introduced due to the coronavirus pandemic on selected aspects of life. The researchers focused on observing changes in habits related to physical activity and their connections with people’s subjective well-being and emotional state.Material and methods. The study was carried out within the international project of the group „IRG on COVID and exercise”. The research tool was a standardized questionnaire.Results. Based on the data collected and the analysis of the percentage results, it can be observed that the overwhelming majority of people taking up physical activity reported a better mood during the pandemic. However, statistical tests do not confirm these relationships due to the small sample size.Conclusions. Isolation favours physical activity. Future, in-depth studies, by enlarging the population group, are necessary to confirm the above observations.

scholarly journals The Role of Dopamine Receptor D2 in Bridging the Intention-Behavior Gap in Sport Participation

2021 ◽  
Vol 18 (5) ◽  
pp. 2379
Author(s):  
Seiyeong Park ◽  
Junhye Kwon ◽  
Chiyoung Ahn ◽  
Hae-Sung Cho ◽  
Hyo Youl Moon ◽  
...  
Keyword(s):  
University Students ◽  
Dopamine Receptor ◽  
Sport Participation ◽  
Small Sample Size ◽  
Behavioral Model ◽  
Small Sample ◽  
Male Students ◽  
Future Research ◽  
Dopamine Receptor D2 ◽  
The Impact

Previous studies have identified that a behavior can occur through the strongest predictor intention, but there is a gap between intention and behavior. Dopamine receptor D2 (DRD2) is known to account for a variance in sporting behaviors in human and animal subjects. However, the relationship between DRD2 and sport participation has been poorly studied, and the limited available reports are inconsistent. The present study was performed to examine the impact of DRD2 on sport participation among Korean university students based on the integrated behavioral model (IBM). Data were collected from enrolled university students in Seoul (N = 45). Participants answered survey questions first, and then they gave investigators their hair to provide DNA information (i.e., the A1 allele of DRD2). DRD2 had a significant effect on sport participation, but only in male students. Male students who carried the A1 allele of DRD2 significantly participated in 105.10 min more sporting activities than male students who did not. Moreover, the effect of intention on sport participation was significantly decreased when considering DRD2. Despite the small sample size, the results of this study could be a preliminary case for a larger study and indicate the direction of future research. Our results suggest that DRD2 may have played an important role as the “actual skill” shown in the IBM.

Nipple Confusion

PEDIATRICS ◽  
1993 ◽  
Vol 92 (2) ◽  
pp. 300-301
Author(s):  
DOREN FREDRICKSON
Keyword(s):  
Breast Feeding ◽  
Statistical Power ◽  
White Women ◽  
Small Sample Size ◽  
False Negative ◽  
Small Sample ◽  
Bottle Feeding ◽  
Feeding Duration ◽  
Breast Feed ◽  
The Impact

To the Editor.— I wish to comment on the study reported by Cronenwett et al,1 which was a fascinating prospective study among married white women who planned to breast-feed. Women were randomly selected to perform either exdusive breast-feeding or partial breast-feeding with bottled human milk supplements to determine the impact of infant temperament and limited bottle-feeding on breast-feeding duration. The authors admit that small sample size and lack of statistical power make a false-negative possible.

The impact of vestibular symptoms and electronystagmography results on recovery from sudden sensorineural hearing loss

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gaelle Vofo ◽  
Marrigje Aagje de Jong ◽  
Michal Kaufman ◽  
Julia Meyler ◽  
Ron Eliashar ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Small Sample Size ◽  
Small Sample ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Caloric Test ◽  
Routine Identification ◽  
The Impact ◽  
Caloric Tests

Abstract Objectives Idiopathic sudden sensorineural hearing loss (SSNHL) represents a frequently encountered otological entity, of various types and severity, with an array of associated symptoms including vertigo. This is a devastating life-changing condition with a blurry prognosis. The objective of this study was to determine the clinical association of vestibular impairment by electronystagmography (ENG) and caloric tests, and their ability to predict prognosis. Methods An observational, crossectional study was carried out amongst patients admitted with SSNHL. Each consenting patient had an audiometry test performed on admission as well as ENG and caloric tests. Treatment included oral steroids and carbogen with intratympanic steroids used only as salvage treatment. Follow-up was completed after 6 months when hearing gains were evaluated. Finally, an association was sought between the rate of recovery and ENG and caloric test results. Results Of 35 patients included, marked recovery was seen in patients without vertigo when compared to those with vertigo (p=0.003). A statistically significant association was found between the presence of vertigo and hearing deterioration (p=0.008). More so, normal electronystagmography results were associated with marked recovery (p=0.04). Conclusions The vestibular end organs are both subjectively and objectively affected in SSNHL as demonstrated by the abnormal ENG and caloric tests in our study despite the small sample size. Concomitant vestibular involvement carries poorer prognosis and routine identification may help foresee the recovery of patients with SSNHL and as such, aid in patient counseling. ENG and caloric tests are easily available and may be recommended for all patients with SSNHL.

CEOs’ accounting-based attributes and earnings management strategies under mandatory IFRS adoption

2018 ◽  
Vol 19 (4) ◽  
pp. 608-625 ◽  
Author(s):  
Amel Kouaib ◽  
Anis Jarboui ◽  
Khaireddine Mouakhar
Keyword(s):  
Earnings Management ◽  
Small Sample Size ◽  
Small Sample ◽  
Moderating Effect ◽  
Audit Committees ◽  
Content Type ◽  
Ifrs Adoption ◽  
Experience Education ◽  
The Impact ◽  
The Relationship

Purpose The purpose of this paper is to focus on the moderating effect of mandatory International Financial Reporting Standards (IFRS) adoption on the relationship between chief executive officer (CEO) experience/education and earnings management in European companies. Design/methodology/approach Data from a sample of 302 European firms listed on Stoxx Europe 600 index and 596 CEOs from 2000 to 2014 are used to test the moderation model using moderation regression analysis. Findings Evidence reveals that CEO’s accounting-based attributes are negatively associated with accruals-based earnings management and positively associated with real earnings management (REM). Further, mandatory IFRS adoption significantly moderates the impact of CEO’s accounting-based traits on earnings-management activities. Research limitations/implications A small number of European firms were studied and, given the long study period, many firms with missing data were eliminated. To avoid a small sample size, countries with few observations were included, which leads to an uneven distribution between observations per country. Practical implications Findings from this paper can help: European firms to consider demographic traits when recruiting or promoting executives; the IASB to improve enforcement mechanisms and make IFRS implementation mandatory; and audit committees to effectively monitor REM. Originality/value This study is unique in providing European evidence for the moderating effect of mandatory IFRS adoption on the relationship between CEOs’ accounting experience/education and earnings management activities. This paper is also relevant as it addresses the effectiveness and efficiency of accounting literates.

scholarly journals Congenital Micropenis: Aetiology And Management

2021 ◽  
Author(s):  
Marianna Rita Stancampiano ◽  
Kentaro Suzuki ◽  
Stuart O’Toole ◽  
Gianni Russo ◽  
Gen Yamada ◽  
...  
Keyword(s):  
Racial Differences ◽  
Small Sample Size ◽  
Small Sample ◽  
Long Term Outcomes ◽  
Penile Length ◽  
Appearance Quality ◽  
Wide Range ◽  
The Impact

Abstract In the newborn, penile length is determined by a number of androgen dependent and independent factors. The current literature suggests that there are inter-racial differences in stretched penile length in the newborn and although congenital micropenis should be defined as a stretched penile length of less than 2.5SDS of the mean for the corresponding population and gestation, a pragmatic approach would be to evaluate all boys with a stretched penile length below 2 cm, as congenital micropenis can be a marker for a wide range of endocrine conditions. However, it remains unclear as to whether the state of micropenis, itself, is associated with any long-term consequences. There is a lack of systematic studies comparing the impact of different therapeutic options on long-term outcomes, in terms of genital appearance, quality of life and sexual satisfaction. To date, research has been hampered by a small sample size and inclusion of a wide range of heterogeneous diagnoses; for these reasons, condition specific outcomes have been difficult to compare between studies. Lastly, there is a need for a greater collaborative effort in collecting standardized data so that all real-world or experimental interventions performed at an early age can be studied systematically into adulthood.

scholarly journals The impact of visual impairment on nutritional status: A systematic review

2018 ◽  
Vol 36 (1) ◽  
pp. 17-30 ◽  
Author(s):  
Nabila Jones ◽  
Hannah Bartlett
Keyword(s):  
Nutritional Status ◽  
Visual Impairment ◽  
Sample Size ◽  
Visually Impaired ◽  
Small Sample Size ◽  
Small Sample ◽  
Control Group ◽  
Visually Impaired People ◽  
Impaired People ◽  
The Impact

The aim of this review was to evaluate the literature that has investigated the impact of visual impairment on nutritional status. We identified relevant articles through a multi-staged systematic approach. Fourteen articles were identified as meeting the inclusion criteria. The sample size of the studies ranged from 9 to 761 participants. It was found that visual impairment significantly affects nutritional status. The studies reported that visually impaired people have an abnormal body mass index (BMI); a higher prevalence of obesity and malnutrition was reported. Visually impaired people find it difficult to shop for, eat, and prepare meals. Most studies had a small sample size, and some studies did not include a study control group for comparison. The limitations of these studies suggest that the findings are not conclusive enough to hold true for only those who are visually impaired. Further studies with a larger sample size are required with the aim of developing interventions.

Impact of race on biomarker testing among HER2- advanced breast cancer (ABC) patients (pts) in the United States: Results from a real-world study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10598-10598
Author(s):  
Reshma L. Mahtani ◽  
Alexander Niyazov ◽  
Katie Lewis ◽  
Lucy Massey ◽  
Alex Rider ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Small Sample Size ◽  
The United States ◽  
Small Sample ◽  
Access To Treatment ◽  
History Of ◽  
Biomarker Testing ◽  
Abstract Data ◽  
The Impact

10598 Background: African Americans (AA) have the highest breast cancer (BC) mortality rate. Access to treatment is a known contributing factor. In the past 4 years, several targeted therapies for HER2- BC have become available which require testing for specific biomarkers. This study assessed the impact of race on biomarker testing rates in HER2- ABC pts receiving treatment in the US. Methods: Oncologists were recruited to abstract data from medical charts for the next 8-10 pts receiving treatment with HER2- ABC during Sept 2019-Apr 2020. Pts records were stratified by race and categorized into 3 mutually exclusive cohorts [White/Caucasian (White), AA, Other]. The other race cohort was excluded from this analysis due to small sample size. Differences in pt demographics/clinical characteristics were analyzed via Fisher’s exact tests. Testing rates for actionable biomarkers (i.e. BRCA1/2, PIK3CA, PD-L1) were compared between White and AA pts utilizing logistic regressions controlling for age, known family history of a BRCA-related cancer, hormone receptor (HR) status and practice setting (academic vs. community). Further analyses by age will be presented. Results: This analysis included 378 pts records, provided by 40 oncologists. Mean age was 64 years; 77% had HR+/HER2- ABC; 20% had advanced triple negative breast cancer (TNBC), 3% had ABC with an unknown HR status. Compared to White pts, AA pts were significantly more likely to have advanced TNBC (27% vs. 18%, p<0.05). Compared to White pts, AA pts had significantly lower BRCA1/2 mutation (mut) testing rates (Table). Numerically lower rates of PIK3CAmut and PD-L1 testing were observed among AA pts (Table). BRCA1/2mut positivity rate (germline [g] and/or somatic [s]) was higher among AA vs. White pts (30% vs. 22%). Positivity rate for PIK3CAmut was lower for AA vs. White pts (8% vs. 11%). Conclusions: A higher than expected BRCA1/2mut positivity rate was observed than previously reported in the literature. This is likely because this analysis included s BRCA1/2mut and represented a high risk pt population. Across all biomarkers assessed, AA pts had lower testing rates than White pts. This suggests racial disparities in testing rates of actionable biomarkers. Consistent with guidelines, and with the increased availability of targeted therapies, focused efforts should be developed to increase biomarker testing in AA pts. Funding: Pfizer Biomarker Testing Rates by Race.[Table: see text]

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