Livin, a regulator of apoptosis protein, is deregulated in melanoma and serves as an independent prognostic factor—a study of 114 melanoma patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21006-21006
Author(s):  
I. Lazar

21006 Background: Inhibitor of Apoptosis Proteins (IAP) family members inhibit apoptosis mainly by direct binding and inhibition of caspases. We previously identified the IAP Livin and demonstrated that following strong apoptotic stimuli the protein was cleaved by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity. We also demonstrated that Livin is overexpressed in melanoma (M) and plays a role in chemoresistance and survival. More recently we identified synonymous single nucleotide polymorphism (SNP) in Livin at position 528(C/T) that determines expression levels of Livin protein. We found that Livin is expressed in a monoalleic manner. Normal heterozygous samples express the 528T mRNA allele and the Livin protein is not expressed. The monoallelic regulation is lost in metastatic M and the Livin protein is expressed. Methods: This study included 114 M patients that were grouped into clinical categories according to prognosis. Correlation between Livin expression and clinical parameters was examined using ANOVA, chi-square test and Kaplan-Mayer curves. Results: We found that in primary cultures from 114 M patients high, low and absence of Livin protein expression were associated with the T/C, CC and TT genotypes, respectively, at the 528(C/T) polymorphic site. Correlation of Livin expression with overall survival was significant: high expression of the Livin protein was associated with bad prognosis; survival in patients with medium expression of Livin was significantly longer compared with those without livin expression For 23 patients samples were obtained both at diagnosis and upon disease progression. All 23 first tumor sample did not express the Livin protein. Remarkably, Livin was expressed in second tumor samples from 9 of the 23 patients.and was associated with poor prognosis. Conclusions: We found that Livin expression is an independent prognosis factor in malignant M. furthermore, we describe a direct correlation between the level of Livin protein expression and survival of M patients. We also provide evidence for a novel mechanism associating synonymous SNP with control over protein expression and its deregulation during tumor progression. No significant financial relationships to disclose.

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jose D. Tovar-Parra ◽  
Luz D. Gutiérrez-Castañeda ◽  
Sebastián R. Gil-Quiñones ◽  
Jhon A. Nova ◽  
Leonardo Pulido

Introduction. Melanoma is the most aggressive type of skin cancer, with poor prognosis in advanced stages. The incidence and mortality rates have increased in recent years. Single nucleotide polymorphisms p.R24P, p.M53I, p.G101W, p.V126D, and p.A148T in the CDKN2A (HGNC ID: 1787) gene have been associated with the development of melanoma in different populations; however, this association has not been studied in Colombia. Methods. Cutaneous melanoma patients and healthy controls (85 cases and 166 controls) were included in this study. These subjects were screened through HRM-qPCR assay and detected variants in exon 1 and 2 of CDKN2A gene and confirmed with Sanger sequencing. Chi-square test was used to compare allele and genotype distributions between cases and controls. Odds ratio (OR) with 95% confidence interval (CI) was calculated to determine the association between polymorphisms and haplotypes with melanoma susceptibility. Statistical and haplotype analyses were performed using Stata® and R-Studio®. Results. Fifty-four percent of women were identified both in cases and controls. The frequencies of melanoma subtypes were 36,47% lentigo maligna, 24,71% acral lentiginous, 23,53% superficial extension, and 15,29% nodular. Variants in the CDKN2A gene were 11.76% in cases and 8.43% in controls. The most frequent was p.A148T in 5.88% of cases and in 4.82% of controls. GGTTG haplotype showed statistically significant differences between cases and controls ( p value = 0.04). Conclusion. CDKN2A polymorphisms p.G101W, p.R24P, p.M53I, and A148T are not associated with melanoma susceptibility in the Colombian population; further studies regarding genetic interaction and additive effects between more variants are required.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22035-e22035
Author(s):  
C. F. Singer ◽  
G. Hudelist ◽  
E. Fuchs ◽  
W. Köstler ◽  
A. Fink-Retter ◽  
...  

e22035 Background: HER-2 amplification and consecutive overexpression is a predictor for poor prognosis in breast cancer patients. In addition, incomplete resection of HER2 overexpressing tumors leads to increased proliferation of residual breast cancer cells. While the local release of cytokines is thought to be responsible for the malignant behaviour of remaining tumor tissue, the exact mechanism is still unknown. Methods: We have analyzed EGFR, activated (p)EGFR, and activated (p)HER2 protein expression in HER2 overexpressing and in non-HER2 overexpressing tumors from patients who underwent breast surgery and consecutive reexcision for involved margins, and compared expression levels by IHC. Results: While overall HER2 protein expression in the initial and the reexcised sample were comparable, we observed an increase in pHER2 in DCIS in both, HER2 overexpressing (16/21 vs 24/24; p=0.018, Chi Square test) and non-HER2 overexpressing tumors (3/28 vs 5/12; p=0.025, Chi Square test). pHER2 was not increased in invasive tumors, regardless on whether the samples had been taken from a HER2 overexpressing (9/25 vs 6/17; p=0.261, Chi Square test), or a non-HER2 overexpressing tumor (1/27 vs 0/8; p=0.581, Chi Square test). EGFR expression was only detected in 1/47 HER2 overexpressing primary tumors and 2/48 non-HER2 overexpressing tumors, and was undetectable in reexcised specimen. Conclusions: Taken together, we have demonstrated an increase in HER2 receptor activation in incompletely resected preinvasive breast cancer. We hypothesize that receptor phosphorylation is caused by growth factor stimulation in response to intraoperative tissue damage, and perioperative inhibition of specific cytokines could become a promising therapeutic strategy. No significant financial relationships to disclose.


2019 ◽  
Vol 2 (2) ◽  
pp. 16-20
Author(s):  
Kristina Meljanac Salopek ◽  
Stanko Jukić ◽  
Damir Babić

Introduction: Various reports suggest linkage of protein expression to HPV status in cervical carcinomas. The aim of this study was to determine a possible association between HPV type, protein expression and DNA content in both preinvasive (CIN III) and invasive squamous cell carcinoma (SCC) of the cervix, as well as differences between the studied groups in these parameters. Materials and methods: Sections of formalin-fixed paraffin-embedded tumor tissue from 47 cases of CIN III and 60 cases of invasive SCC of the cervix were subjected to HPV genotyping using LiPA (Line immuno-probe assay) and Flow cytometry for DNA content analysis. Also, immunohistochemical staining was performed. Obtained data were analyzed in SPSS using the Chi square test. Results: The major difference (p=0.007) between CIN III and invasive SCC of the cervix was found in DNA content - more aneuploid and tetraploid cases in invasive SCC of the cervix compared to CIN III. Although we observed a similar distribution of studied parameters in both groups, no statistically significant association was found between these parameters, except for p53 and pRb (p=0.018). Conclusion: The studied groups differ in DNA content. A significant association between analyzed parameters was observed in Invasive SCC of the cervix between p53 and pRb expression.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19025-e19025
Author(s):  
Rachit Kumar ◽  
Sarika Khanna ◽  
Patricia Reutemann ◽  
Kurt S Wenk ◽  
Suraj S. Venna ◽  
...  

e19025 Background: Vitamin D (VitD) is synthesized in the skin as a result of exposure to sunlight and its deficiency is common in the general population as well as in cancer patients. Sun protection is strongly recommended for patients after a melanoma diagnosis. We conducted a pilot study to assess the prevalence of VitD deficiency and the impact of both sun protective behavior and VitD supplementation on VitD levels in melanoma patients Methods: Adult patients with AJCC Stage 0-III melanoma were recruited from the Washington Cancer Institute between July 2011 and January 2012. Subjects completed a questionnaire asking about oral VitD supplementation and sun protective behaviors. VitD deficiency was defined by a 25-hydroxyvitamin D (25(OH)D) level less than 30ng/mL. Pearson Chi-square test and multivariate logistic regression were used to determine predictors of VitD deficiency. Results: A total of 49 participants (20 males, 29 females) completed the questionnaire and provided a blood sample for 25(OH)D determinations. Median age was 52 years (23-82), and most (n=48, 98%) were Caucasian. The majority had either stage 0 (n= 13, 27%) or 1 (n=29, 59%) melanoma. Twenty-six (53%) reported regular use of VitD supplements, and the majority reported sun protective behaviors (n=36, 73%). The prevalence of VitD deficiency was 46% (n=23). VitD deficiency was more common in patients who were not taking VitD supplementation (73% vs. 26%, p<0.01). Other associations include: (1) BMI>25 vs. BMI ≤25 (57% vs. 33%, p=0.10); (2) winter vs. summer months(54% vs. 40%, p=0.34); (3) those who practiced sun protective behavior vs. not (50% vs. 38%, p=0.48). On multivariate analysis, the use or non-use of VitD supplementation remained the only significant predictor of VitD deficiency (OR=0.11, p<0.01). Conclusions: VitD deficiency is common in melanoma patients especially in those who are not on VitD supplementation.


2018 ◽  
Vol 5 (1) ◽  
pp. 3442-3447
Author(s):  
Budhi IB ◽  
Metria IB ◽  
Hanafi B ◽  
Herri SS ◽  
Effendi JS

Background : The incidence of colorectal malignancies at a young age, and the absence of sufficient data to explain about it, including in terms of gene mutations that play a role.  The research will be done here is to determine whether changes in mRNA expression of genes DCC ( deleted in colorectal cancer ) and p53 play a role in colorectal malignancy is less than 40 years of age.  Researchers also will perform immunohistochemistry to look at protein expression of the gene and protein expression was evaluated whether these correlated with mRNA expression. Methods : This study is an observational analytic cross sectional design, carried out in the Laboratory of Biomedical Faculty of Medicine Sebelas Maret University from June 2013 to March 2014.  Subjects were 30 patients with stage III colorectal adenocarcinoma, with details of the 15 subjects for each group.  Subjects taken by consecutive sampling.  Immunohistochemical examination of paraffin block preparation and reverse transcriptase - polymerase chain reaction (RT - PCR) of tumor tissue samples for evaluation of the presence of the protein and mRNA expression of DCC and p53 genes .Statistical analysis using the chi-square test and Phi correlation.  Results : the 4 subjects in the age group ≤ 40 years was not accompanied by DCC protein expression while in the age group > 40 years of protein expression obtained in all preparations.  Expression of p53 protein more available in the age group > 40 years ( 3 subjects ), in the age group ≤ 40 years is only found in 1 subject. Examination results of RT-PCR to assess the mRNA expression results are consistent with the results of immunohistochemistry.  Eleven subjects from the age group ≤ 40 years obtained DCC mRNA expression, whereas p53 mRNA expression was found in 12 subjects.  From  statistical analysis using the chi-square test and Phi correlation, we found significant association between protein and mRNA expression of DCC with colorectal cancer aged ≤ 40 years.  Correlation of test results, obtained significant correlation between mRNA expression of DCC with colorectal cancer aged ≤ 40 years and the results of protein expression were significantly correlated with mRNA expression of DCC and p53 genes.  Conclusion : the expression of p53 protein and mRNA did not play a role in colorectal cancer ≤ 40 years of age. Protein expression was positively correlated with mRNA expression .


1970 ◽  
Vol 5 (2) ◽  
pp. 64
Author(s):  
Eny Sendra ◽  
Dewi Indriani

Breast feeding is giving milk to be drunk to the baby from the breast. Uterus involution is a process how the uterus return to the condition back, before pregnanting after bearing. At the moment of suckling, happens a stimulus and brings the hormones out, such as oksitosin uses not only to stimulate some muscles constraction but also to stimulate the uterus, so that the process of uterus involution happens foster. According to the explanations above, the research aimed to know about the correlation between breast feeding and uterus involution. This research’s design was, cross sectional by the population of all childbirth mothers approximately 50 persons / month. By using accidental sampling technique we got 21 sample respondents. The place of research in RSIA Aura Syifa in Kediri Regency on 16th until 22nd of June 2009. From this research’s result, we got 14 persons (66,67%) with normal uterus involution, suckled in a good way, one person (4,67%) with normal uterus involution, suckled in a wrong way, 2 persons (9,52%) with abnormal uterus involution, suckled in a good way and 4 persons (19,05%) with abnormal uterus involution, suckled in a wrong way. Statistic test which used chi-square test, counted the probability frequency in advance, from that we got 3 columns with the score, less than 5, so that chi-square can not be continued and by doing exact fisher test, the score was 0,001. Because P with the grade mistake 0,05 smaller, so the conclusion was “Ho” is rejected, it meant “there was correlation between suckling and uterus involution”. Key Word : Breast feeding, uterus involution


2020 ◽  
Vol 5 (3) ◽  
pp. 875
Author(s):  
Asfri Sri Rahmadeni

<p class="Normal1"><em>Commitment is the attitude or behavior of likes or dislikes shown by someone against the organization at work. Indonesia is recorded as a nurse who has a low organizational commitment (76%) so it harms services. This phenomenon in the hospital can be seen from the indicator of the high turnover rate of nurses which reaches 30.9% which exceeds the standard &lt;5%. Many factors affect organizational commitment. The purpose of this study was to analyze the Personal Factors Associated with Organizational Commitment of Hospital Nurses. This study is a cross-sectional analytic study and purposive sampling technique with a sample of 59 nurses. Chi-Square test results obtained personal factors that have a relationship with organizational commitment Nurse Hospital is age with p = 0,000 and education with p = 0,000, personal factors not related to organizational commitment are gender p = 1,053 and years of service with p = 1,147. Hospitals should conduct research/surveys on Organizational Commitment periodically as an evaluation material in the context of the organization's development and development in the future</em>.</p>


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Abdurrakhman abdurrakhman Abdurrakhman

ABSTRACT : The House index and Container Index in the buffer area of ​​the working area of ​​Balikpapan Sepinggan Airport is still above 1%, so the potential for the spread of dengue disease. Mobilization of people, goods and transportation equipment will increasingly affect the transmission of disease in ports and airports, especially for vector-borne diseases. This study aims to analyze the risk factors associated with larvae density of Aedes aegypti and describe the larvae index in the buffer zone of the Sepinggan Balikpapan Airport This study was a descriptive study with a cross sectional design. The sample in this study was 121 houses with a proportionate stratified random sampling, the research location was in the buffer zone of Sepinggan Balikpapan Airport in November 2018. The variables studied were houses with positive larvae containers, breeding sites and PSN behavior and larvasidation. The data was analyzed using the chi square test. There was a relationship between houses with larvae positive Aedes aegypti, behavior of Mosquito Nest Eradication (PSN) and larvasidation with larvae density of Aedes aegypti but not for breeding sites (p = 0.00 and 95% CI = 0.64), and   (p = 0.00 and 95% CI = 0.34). The description of several Aedes aegypti larvae index, namely House Index (HI) = 57.02%, Container Index (CI) = 24.36%, Bruteau Index (BI) = 148.76, and Flick Free Numbers (ABJ) = 42.98 %. Houses with larvae of Aedes aegypti larvae and PSN and larvasidation behavior were associated with larvae density of Aedes aegypti. The index of HI, CI and BI larvae is of high value so there is a risk of DBD transmission


2019 ◽  
Vol 3 (2) ◽  

Radiographic Mandibular Indices serve as easy and relatively cheap tools for evaluating bone mineralization. Objectives: To examine the effect of age and gender on three mandibular indices: the panoramic mandibular index (PMI), the mandibular ratio (MR) and the mandibular cortical index (MCI), among Libyan population. Methods: The three indices were measured on 317 digital (OPGs) of adult humans (155 males, 162 females). The sample was divided into six age groups (from 18-25 years through 56-65 years). The measurements were analyzed for interactions with age and sex, using SPSS (Statistical Package for Social Studies) software version no. 22. The tests employed were two way ANOVA, the unpaired T-test and chi-square test. Results: The mean PMI fluctuated between 0.37 s.d. 0.012 and 0.38 s.d. 0.012. among the sixth age groups. One-way ANOVA statistical test revealed no significant of age on PMI. On the other hand gender variation has effect on PMI, since independent sample t-test disclosed that the difference between the male and female PMI means statistically significant. ANOVA test showed that the means of MR among age groups showed a negative correlation i.e. MR mean declined from 3.01 in 18-25 age groups to 2.7 in 55-65 age groups. In contrary, the gender showed no effect on MR according two sample t-test at p> 0.05. In regards with MCI, statistical analysis showed that it affected by age that is C1 was decreasing by age while C2 and C3 were increased by age. Using chi square test the result indicated that there is a significant difference among the different age group and the two genders in MCI readings. Conclusion: PMI was influenced significantly by age but minimally by the gender. MR is not affected by gender but has a negative correlation with age. MCI is affected by both age and gender


2019 ◽  
Vol 7 (2) ◽  
pp. 115
Author(s):  
Dini Yuliansari

The well is one of the source water used for bathing, washing, and drinking by the citizens in Jiken Hamlet, Rarang Village, Terara Sub-District. Poor dug well construction conditions can affect the amount of coliform bacteria contained in the dug well water. The purpose of this study is to identify the construction of dug wells and the content of coliform bacteria in dug well water and determine the relationship between dug well construction and the content of coliform bacteria. This research is analytic with a cross sectional study design. The results were obtained from 11 samples of dug wells which were observed in construction and the coliform content was known that all samples did not requirements as good dug well construction. Coliform content test results showed that as many as 5 dug well water samples did not pass the clean water quality standards. The results of data analysis with the chi-square test variable construction of dug wells with coliform content variable  showed 0,172 > 0,05, then the concluded is the dug well not suitable to use by people in that area as a source of water for daily needs.


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