Genomic alterations in visceral versus nonvisceral “metastatic” site tumor tissue in metastatic prostate cancer (mPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 167-167
Author(s):  
John Esther ◽  
Umang Swami ◽  
Jonathan Chipman ◽  
Taylor Ryan McFarland ◽  
Andrew W Hahn ◽  
...  

167 Background: Men with mPC with visceral metastasis, as compared to non-visceral disease have inferior outcomes regardless of therapy (PMID: 25403629). Herein, we hypothesize that visceral versus non-visceral metastasis sites differ with regards to underlying genomic alterations (GA). These GA possibly drive metastasis to visceral sites and mediate a more aggressive disease. Identifying these GA may guide future trial designs by better stratifying patients and predicting therapy responses. Methods: In this retrospective analysis, inclusion criteria were: diagnosis of mPC and comprehensive genomic profiling of metastatic tissue by CLIA certified lab. Liver and lung were defined as visceral while bone and lymph nodes were defined as non-visceral metastasis. Evaluated GA were p53, RB1, PTEN, AR, TMB, CDK12, SPOP, MYC, MET, BRCA genes, BRAF, ARID1A. Fisher’s Exact Test was used to compare GA in visceral and non-visceral tumor tissue. Results: Overall 54 men with mPC with visceral (n=8) and non-visceral (n=46) metastatic tissue biopsies were evaluated. Visceral biopsies included liver (3) and lung (5). Non-visceral biopsy sites included lymph nodes (33) and bone (13). Men with or without visceral metastasis had similar baseline characteristics (Fisher’s Exact Test and Wilcoxon Rank Test; Table). Visceral tumor tissue had a significantly greater odds of having RB1 mutation [OR = 12.09; 95% CI = (1.12, 178.21); p-value 0.02] as compared to non-visceral tumor tissue. Conclusions: RB1 GA were more common in visceral as compared to non-visceral metastatic sites in mPC. RB1 loss is associated with ineffectiveness to CDK4/6 inhibitors (PMID 26633733). These hypothesis-generating data suggest that men with mPC with visceral metastasis may not optimally benefit by enrollment on CDK4/6 inhibitor trials. BLM, NA: equal contribution.[Table: see text]

2012 ◽  
Vol 78 (6) ◽  
pp. 693-697
Author(s):  
Alfred John Colfry ◽  
Xu Zhang ◽  
George M. Fuhrman

We hypothesize that the diminishing role of axillary node dissection (ALND) in early stage breast cancer could be further reduced in patients with advanced disease depending on the response to neoadjuvant chemotherapy (NC). We reviewed records of patients managed with NC and recorded demographics, tumor characteristics, pre/postoperative axillary nodal status, and NC response. We define a response to NC as follows: T2 tumors at least a 50 per cent reduction in the product of the length and width of the tumor and in T3–4 tumors a reduction in tumor size to less than 2 cm. We defined a negative axillary nodal status as either a negative sentinel node biopsy before or after NC or a negative ALND. We defined a positive axillary nodal status as clinical persistence of nodal disease despite NC or involved nodes determined by ALND. Fisher's exact test was used to evaluate the association between response to NC and nodal status. Over the past 4 years, 35 patients have completed NC and surgical treatment including lymph node assessment. Sixteen cancers demonstrated a response to NC and two (12.5%) had positive lymph nodes. Nineteen cancers failed to respond to NC and 13 (68.4%) had involved lymph nodes. Fisher's exact test shows a strong association between NC response and nodal status (two-tailed P value 0.0016). Patients with advanced locoregional breast cancer that respond to NC are unlikely to benefit from ALND. If this study's findings are confirmed in larger trials, ALND could be limited to patients with advanced locoregional breast cancer unresponsive to NC.


2020 ◽  
Vol 9 (1) ◽  
pp. 111-118
Author(s):  
Lumastari Ajeng Wijayanti ◽  
Eny Sendra ◽  
Ratih Novitasari ◽  
Tanti Dwi Pujaningsih

This research used cross sectional design. The population was 194 respondents and the sample was 54 respondents which are taken by using simple random sampling technique. Independent variable in this research was demographic status that was measured by questionnaire and nutritional status that was measured based on Body Mass Index (BMI). Meanwhile, dependent variable in this research was the occurrence of anemia that was measured by using spectrophotometry. Data analysis used Fisher's Exact test and Two-Sample Kolmogorov-Smirnov test (α = 0,05). Result of Fisher's Exact test was obtained that p value = 1,000 > 0,05, which meant that there was no significant correlation between demographic status and the occurrence of anemia. Meanwhile, result of Two-Sample Kolmogorov-Smirnov test was obtained that p value = 0,017 < 0,05, which meant that there was a significant correlation between nutritional status and the occurrence of anemia.


Author(s):  
M Zamzani ◽  
Hamam Hadi ◽  
Dewi Astiti

<p><strong>ABSTRACT</strong></p><p><strong><em>Background</em></strong><strong><em>s</em></strong><strong><em>:</em></strong><em> The increasing prevalence of obesity is caused by imbalance between energy input to energy output. Physical activity in children both at school and at home plays an important role in determining the nutritional status of children, including the risk of obesity. </em></p><p><strong><em>Objectives:</em></strong><em> To determine the relationship between children physical activity with obesity in Ngebel Elementary School, Tamantirto Kasihan Bantul. </em></p><p><strong><em>Methods:</em></strong><em> This study was an observational study with cross sectional design. The study population is all children grades 3, 4, and 5 Ngebel Elementary School, Tamantirto Kasihan Bantul. These samples included 96 children who met the inclusion and exclusion criteria obtained with less total sampling technique. Weight children measured using digital bathroom scales to the nearest 0.1 kg and height was measured using the nearest 0.1 cm microtoice assisted by trained enumerators. Physical activity data were obtained using a physical activity questionnaire was adopted from previous studies. Nutritional status data is calculated using the WHO software Anthro 2005. Univariate analysis using frequency distribution and bivariate analysis using </em><em>Fisher’s Exact Test</em><em>. Data were analyzed using software statistic.</em></p><p><strong><em>Results:</em></strong><em> Results analisis showed physical activity had a significant relationship with the incidence of obesity in children, with p Value 0.015 (&lt;0,05) with OR of 4.78 (95% CI: 1.36 to 16.82), </em><em>in other words children who do moderate to severe activity ≤1 hour/day had 5 times higher chance to be obese than children with moderate to severe activity &gt;1 hour/day.</em></p><p><strong><em>Conclusions:</em></strong><em> Physical activity has a significant association with obesity.</em><em> </em></p><p><strong>KEYWORDS<em>:</em></strong><em> physical activity, obesity, elementary school children</em><em></em></p><p> </p><p><strong>ABSTRAK</strong></p><p><strong><em>Latar belakang: </em></strong><em>Peningkatan prevalensi obesitas disebabkan oleh adanya ketidakseimbangan antara masukan energi dengan keluaran energi. Aktivitas fisik pada anak-anak baik di sekolah maupun di rumah berperan penting dalam penentuan status gizi anak, termasuk risiko terjadinya obesitas.<strong></strong></em></p><p><strong><em>Tujuan: </em></strong><em>Untuk mengetahui </em><em>hubungan antara aktivitas fisik dengan kejadian obesitas pada anak Sekolah Dasar Negeri Ngebel, Tamantirto Kasihan Bantul.</em></p><p><strong><em>Metode: </em></strong><em>Penelitian ini merupakan penelitian observasional dengan rancangan cross sectional. Populasi penelitian adalah semua anak kelas 3, 4, dan 5 SDN Ngebel, Tamantirto Kasihan Bantul. Sampel penelitian berjumlah </em><em>96 </em><em>anak yang memenuhi kriteria inklusi dan eksklusi diperoleh dengn teknik total sampling. Berat anak-anak diukur dengan menggunakan timbangan injak digital dengan ketelitian 0,1 kg, sedangkan tinggi badan diukur menggunakan microtoise dengan ketelitian 0,1 cm dibantu oleh enumerator terlatih. Data aktivitas fisik diperoleh menggunakan kuesioner aktivitas fisik yang diadopsi dari</em><em> penelitian sebelumnya</em><em>. Data status gizi dihitung dengan menggunakan software WHO Anthro 2005. Analisis univariat menggunakan distribusi frekuensi dan analisis bivariat menggunakan</em><em> Fisher’s Exact Test</em><em>. Data dianalisis dengan menggunakan program software statistic.</em></p><p><strong><em>Hasil: </em></strong><em>Hasil a</em><em>nalisis </em><em>menunjukkan aktivitas fisik memiliki hubungan yang signifikan dengan kejadian obesitas pada anak dengan </em><em>nilai p value 0,009 (&lt;0,05) dengan nilai OR 5,69 (95% CI: 1,42-22,65), dengan kata lain anak yang melakukan aktivitas sedang-berat ≤1 jam/hari berpeluang 5 kali lebih besar untuk mengalami obesitas daripada anak dengan aktivitas sedang-berat &gt;1 jam/hari.</em></p><p><strong><em>Kesimpulan: </em></strong><em>Aktivitas fisik memiliki hubungan secara bermakna dengan obesitas.</em><strong><em></em></strong></p><p><strong>KATA KUNCI: </strong><em>aktivitas fisik, obesitas, anak SD</em></p>


Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 255 ◽  
Author(s):  
Enrica Marchionni ◽  
Maria Grazia Porpora ◽  
Francesca Megiorni ◽  
Ilaria Piacenti ◽  
Agnese Giovannetti ◽  
...  

Background: Endometriosis is a widespread multifactorial disease in which environmental, genetic, and epigenetic factors contribute to the phenotype. Single Nucleotide Polymorphisms (SNPs) in genes implicated in pivotal molecular mechanisms have been investigated as susceptible risk factors in distinct populations. Among these, Toll-like receptor 4 (TLR4) represents a good candidate due to its role in the immune/inflammatory response and endometriosis pathogenesis. Methods: The TRL4 gene T399I SNP (C/T transition, rs4986791) was investigated in 236 Italian endometriosis patients and 150 controls by using the PCR-RFLP method. One-tailed Fisher’s exact test was used to compare differences between categorical variables. T399I genotype distribution was evaluated for Hardy–Weinberg equilibrium in both groups using the Chi-squared test for given probabilities. Results: Fisher’s exact test comparing C and T allele frequencies showed a difference in the frequency of T alleles between patients and controls (OR = 1.96, 95% confidence interval 0.91–4.23; p-value = 0.0552). Genotype frequencies did not show any significant difference between patients and controls. The homozygous TT genotype was observed in 2% of endometriosis women and not in controls. Conclusions: Our results show that the TLR4 rs4986791 T variant may be considered a genetic risk factor for endometriosis in Italian women. More extensive studies in other populations are needed to confirm this result.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7624-7624
Author(s):  
P. A. Zucali ◽  
M. Gallegos Ruiz ◽  
E. Giovannetti ◽  
A. Destro ◽  
K. Floor ◽  
...  

7624 Background: Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) show anti-tumor activity in only 10% of Caucasian non-small cell lung cancer (NSCLC) patients. Aim of this study was to evaluate several biological parameters potentially related to EGFR, including c-Met activation, as potential markers of intrinsic resistance to EGFR-TKIs in NSCLC. Methods: P-Akt, p-Erk, c-Src, E-Cadherin, c-Met[pY1003] and c-Met[pY1230/1234/1235] status was immunohistochemically determined on a tissue micro-array of tumor samples from 51 NSCLC patients treated with gefitinib. EGFR, k-ras, and c-Met mutation analysis was also carried out. A panel of NSCLC cell lines expressing c-Met[pY1003] were treated with gefitinib (0.01–100μ M) alone or in combination with hepatocyte growth factor (40 ng/ml) and the c-Met-agonistic antibody DN-30 (80 μg/ml) for 72 hours in 0.5% FCS medium. Drug interaction between gefitinib and DN-30 was assessed, at a non-constant concentration ratio, using the combination index (CI) method. Results: There was no association between p-Erk, c-Src, E-Cadherin, c-Met[pY1230/1234/1235], and k-ras status and response or survival. EGFR exon 19 deletion and p-Akt nuclear staining were significantly associated with response (P<0.0001; Fisher's exact test) and longer time to progression (TTP) (P=0.007; log-rank test), respectively. High c-Met[pY1003] membrane staining was significantly associated with progressive disease (P=0.019; Fisher's exact test) and shorter TTP (P=0.0416; log-rank test), but not with survival. Multivariate analysis confirmed a significant relationship between c-Met[pY1003] and increased risk of disease progression (HR=2.464, 95% CI 1.293–4.696, P=0.006). No c-Met mutations were found. In vitro, the combination with DN- 30 synergistically (CI<1) enhanced gefitinib-induced growth inhibition in all c-Met[pY1003]-expressing NSCLC cells studied (H460, SW1573, A549 and H292). Conclusions: Activation of c-MET may be a biological marker of intrinsic resistance to gefitinib in NSCLC patients, and combined inhibition of c-Met and EGFR may be a suitable therapeutic approach in patients with activated c-Met[pY1003] tumors. No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13112-e13112
Author(s):  
Ricardo H. Alvarez ◽  
Rebecca Rollins ◽  
Joe Ensor ◽  
Daniel W. Nixon ◽  
Jonathan Ramey ◽  
...  

e13112 Background: Disparities in breast cancer (BC) care still clearly exist among Whites (W) and African-Americans (AA) racial groups. These disparities resulting in higher mortality among AA compared to W. The objective of this analysis was to estimate the prevalence of BC subtypes in a population-based sample of BC cases, collected in a Breast Cancer Database (BCD) and to examine correlations with demographic and clinicopathologic variables and patient survival. Methods: retrospective analysis of patients registered at BCD was performed. Pts with BC were analyzed for differences in survival based on histologic subgroup (HS), race and BMI. Median Kaplan Meyer estimate for potential follow-up was 13.1 months with 95% CI (10.6, 15.0). Univariate and multivariate analysis were used to identify factors associated with demographic and cancer biology variables. Results: A total of 2,110 patients were registered at BCD and were available for this analysis.The median age at diagnosis was 50.8 years with 95% CI of (50.2, 51.0). 50% were W and 46.6% were AA. HS were classified by immunohistochemistry CLIA central lab, ER+ 61.1%, HER2+ 21.8% and TNBC 17%.Fisher’s exact test showed statistically difference in HS distribution among the races (p < 0.0001); 25% and 11.7% TNBC, for AA and W, respectively. The mean BMI was 29.0 with 95% CI of (29.6, 30.2). BMI characteristics were obese 47.2%, overweight 28.6% and normal 22.2%. Fisher’s exact test showed statistically difference in BMI distribution among the races, 57% and 39% obesity, for AA and W, respectively (p < 0.0001). Log-rank test showed that 2-years OS is worse for TNBC (48%), than for ER+ (72%) and HER2+ (75%). In the multivariable model AA survival was statistically inferior than for W ( p= 0.0094). Cox proportional hazard model was constructed to assess the effect of age, BMI, race and HS (Table). Conclusions: This single institution analysis demonstrated a statistically differences between TNBC, AA, and abnormal BMI as poor prognostic factors in BC pts impacting OS. Further research should investigate how to improve care for AA women who are at higher risk for breast cancer mortality. [Table: see text]


2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Nurhayati Nurhayati

Toilet training sangat penting dalam membentuk karakter anak dan membentuk rasa saling percaya dalam hubungan anak dan orang tua. Keberhasilan toilet training dipengaruhi oleh pengetahuan dan pola asuh orang tua dalam mendorong anak mencapai tujuan yang diinginkan. Penelitian ini bertujuan untuk menganalisis hubungan pengetahuan dan pola asuh orang tua dengan kemampuan toilet training pada anak usia toddler di PAUD Asyiyah 2 Provinsi Sulawesi Tengah. Jenis penelitian ini adalah analitik dengan desain cross sectional. Populasi penelitian ini yaitu semua orang tua yang memiliki anak usia toddler di PAUD Aisyah 2 Provinsi Sulawesi Tengah sebanyak 32 orang. Sampel dalam penelitian ini adalah orang tua yang memiliki anak usia toddler di PAUD Aisyah 2 Provinsi Sulawesi Tengah sebanyak 32 orang dengan teknik pengambilan sampel total sampling. Data dianalisis menggunakan Fisher’s Exact test. Hasil uji Fisher’s Exact didapatkan nilai p=0,000 dan nilai p=0,001 (p Value < 0,05), ini berarti secara statistik ada hubungan pengetahuan dan pola asuh orang tua dengan kemampuan toilet training pada anak usia toddler. Berdasarkan hasil penelitian tersebut disarankan bagi orang tua (ibu) yang menerapkan pola asuh kurang baik agar dapat merubah atau menerapkan pola asuh yang tepat kepada anaknya agar mampu melaksanakan toilet training dengan baik. Kata kunci : Pengetahuan, pola asuh, toilet training.


2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Supriyadi Supriyadi ◽  
Susmini Susmini

Gangguan metabolik mampu menyebabkan beberapa penyakit salah satunya ialah diabetes melitus. Gejala umum yang sering muncul pada kasus diabetes melitus yaitu hiperglikemia. Hiperglikemia yang berkepanjangan dapat mengakibatkan berbagai macam komplikasi diantaranya komplikasi mikrovaskuler dan makrovaskuler. Tujuan penelitian ini untuk mengetahui hubungan kadar gula darah sewaktu dengan gejala neuropati perifer penderita diabetes melitus tipe 2. Desain penelitian ini menggunakan cross sectional. Jumlah sampel 32 penderita diabetes melitus yang dipilih melalui teknik simple random sampling, penelitian ini dilakukan di Desa Kedung Dowo Kecamatan Nganjuk. Berdasarkan uji statistik Fisher’s Exact Test didapatkan p value 0.002 (p value < 0.05) yang berarti terdapat hubungan antara kadar gula darah sewaktu dengan gejala neuropati perifer penderita diabetes melitus tipe 2.


2013 ◽  
Author(s):  
Κωνσταντίνος Τουλής

Σκοπός Με βάση περιπτώσεις μοριακού μιμητισμού μεταξύ των γλυκοπρωτεϊνών και των υποδοχέων τους, διατυπώσαμε την υπόθεση ότι αυτοαντισώματα έναντι του υποδοχέα της θυρεοτροπίνης (TSH-Rab) κατασταλτικού τύπου (blocking) πιθανά να έχουν δραστικότητα αποκλειστή επί του υποδοχέα της ανθρώπινης χοριακής γοναδοτροπίνης (LH/hCG-R) στο ωχρό σωμάτιο, το τελικό βιολογικό αποτέλεσμα της οποίας θα ήταν η απώλεια κύησης κατά το πρώτο τρίμηνο. Ο σκοπός της μελέτης ήταν η κλινική διερεύνηση της παραπάνω υπόθεσης και συγκεκριμένα η διερεύνηση της παρουσίας και εκτίμηση των συγκεντρώσεων bTSH-Rab στις γυναίκες με θυρεοειδίτιδα Hashimoto και ιστορικό καθ’ έξιν αποβολών (ασθενείς) και η σύγκριση τους με γυναίκες με θυρεοειδίτιδα Hashimoto και φυσιολογικό αναπαραγωγικό ιστορικό (μάρτυρες). Ασθενείς και Μέθοδοι Συνολικά επιλέχθηκαν 86 γυναίκες (46 ασθενείς και 46 μάρτυρες με ηλικιακή εξομοίωση) από εξωτερικά ιατρεία και κλινικές του Νομού Θεσσαλονίκης στο πλαίσιο αναδρομικής μελέτης τύπου ασθενών-μαρτύρων. Για τη συμπερίληψη στην ομάδα των ασθενών, η γυναίκα έπρεπε να είχε ηλικία μικρότερη των 35 ετών στην τελευταία αποβολή και κάτω των 50 ετών κατά την επιλογή, χωρίς να εντοπίζονταν από το ιστορικό, την κλινική εξέταση και τον κατά περίπτωση παρακλινικό έλεγχο, δευτεροπαθείς αιτίες καθ’ έξιν αποβολών. Σε υπο-ομάδα των ασθενών (n=15) πραγματοποιήθηκε ορμονολογική εκτίμηση υποφυσιακής λειτουργίας, διακολπικό υπερηχογράφημα πυέλου, καρυότυπο, ανίχνευση μεταλλάξεων του παράγοντα V, μέτρηση επιπέδων ομοκυστεΐνης, αυτοαντισωμάτων έναντι της διπλής έλικας του DNA, αντιπηκτικού του λύκου, β2-γλυκοπρωτείνης και αντικαρδιολιπινικών αντισωμάτων. Η στατιστική ανάλυση πραγματοποιήθηκε με το λογισμικό Stata 10.0 Αποτελέσματα Δεν ανιχνεύθηκε σημαντική διαφορά στον επιπολασμό (Fisher’s exact test, p-value = 1.00) ή στους τίτλους TSH-Rab μεταξύ των ασθενών και των μαρτύρων (Mann-Whitney test, p = 0.59). Οι αναλύσεις ευαισθησίας με βάση τους ορισμούς των καθ’ έξιν αποβολών, των αυτόματων αποβολών, της θυρεοειδίτιδας Hashimoto και της θετικότητας των TSH-Rab δεν τροποποίησαν την κατεύθυνση των ευρημάτων. Η απουσία συσχέτισης μεταξύ TSH-Rab και αναπαραγωγικού ιστορικού επιβεβαιώθηκε σε μονομεταβλητό μοντέλο λογαριθμικής παλινδρόμησης [OR = 1.00, 95% CI = 0.19-5.25], είτε όταν χρησιμοποιήθηκε ο τίτλος των TSH-Rab (OR = 0.77, 95% CI = 0.29 - 2.08). Η παρουσία των TSH-Rab δεν προέβλεψε με στατιστικώς σημαντικό τρόπο τον αριθμό των αυτόματων αποβολών στις ασθενείς (Coef = -0.4, 95% CI = -1.15 - 0.34, p = 0.285) και απουσία συσχέτισης επιβεβαιώθηκε όταν χρησιμοποιήθηκε ο τίτλος τους (Coef = -.0.53, 95% CI = -1.08 - 0.10, p = 0.054). Τα παραπάνω ευρήματα παρέμειναν ανθεκτικά στην ιεραρχική στάθμιση με την ηλικία και το ΒΜΙ κατά την τελευταία κύηση ή αποβολή σε πολυμεταβλητά μοντέλα παλινδρόμησης. Συμπεράσματα Στην παρούσα μελέτη, δεν προέκυψαν ενδείξεις ότι τα TSH-Rab έχουν σημαντικό ρόλο στην παθογένεια των αυτόματων αποβολών και δεν μπορεί να υποστηριχθεί η κλινική και ερευνητική χρησιμότητα της ανίχνευσής τους στις γυναίκες με θυρεοειδίτιδα Hashimoto και ιστορικό καθ’ έξιν αποβολών.


2021 ◽  
Vol 4 (1) ◽  
pp. 102-112
Author(s):  
Sriwani Supardin

Ship sanitation is an indicator of vessel cleanliness, vector control in 2017 no high-risk vessels were found, in 2018 there were 7 high-risk vessels and in 2019 there were 15 high-risk vessels. This study aims to determine the relationship between kitchen sanitation, food raft space and warehouse with cockroach density on ships in the Kendari port area. This type of research is an observational, Cross-Sectional Study design. The population is all ships berthed in the Kendari port area as many as 41 ships and a sample of 37 vessels taken by purposive sampling. Data analysis used fisher's exact test. The results showed that of the 37 ships, the highest density of cockroaches met the requirements (75.7%), the rest did not meet the requirements (24.3%). The kitchen sanitation met the requirements (75.7%), the rest did not meet the requirements (24.3%), then the food raft room sanitation met the requirements (83.8%) and did not meet the requirements (16.2%). Furthermore, warehouse sanitation fulfills the requirements (62.2%) and does not meet the requirements (37.8%). The results of Fisher's exact test obtained p value (0,000). The conclusion of this study is that there is a relationship between kitchen sanitation, food raft space and warehouse with cockroach density on ships in the Kendari port area. Suggestions for the KKP to establish policies to prevent cockroach development.


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