Efficacy of enterotoxigenicEscherichia colivaccine for bovine clinical mastitis

2011 ◽  
Vol 78 (2) ◽  
pp. 149-153 ◽  
Author(s):  
Kazuhide Morimoto ◽  
Madoka Shimizu ◽  
Tomoyasu Kurose ◽  
Keiji Nakatani ◽  
Shinji Akita ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Clinical Mastitis ◽  
Rank Test ◽  
Event Analysis ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Fisher’S Exact Test ◽  
And Control

An enterotoxigenicEscherichia coli(ETEC) vaccine designed to prevent diarrhoea was inoculated into dairy cows, and the occurrence of clinical mastitis was investigated for 2 years. Half of 480 cows in five farms were subcutaneously inoculated with ETEC vaccine (Imocolibov) twice with a 1-month interval in 2007 and 2008. Fisher's exact test and survival (time to event) analysis with the log-rank test were used to compare vaccinates and controls. In 2007, there was no significant difference in the incidence rate of mastitis between vaccinate (20·3%) and control (17·1%) cows. The rate of death or culling due to mastitis was lower in vaccinated cows (7·4%) than in control cows (29·2%,P=0·07, Fisher's exact test;P=0·02, log-rank test). In 2008, there was no significant difference in both the incidence rate of mastitis and the rate of death or culling due to mastitis. Milk productivity was compared between vaccinates and controls in one farm. Multi-way analysis of variance (ANOVA) was performed for the amount of 4% fat-corrected milk, and there was no significant difference between vaccinates and controls. These results suggest that ETEC vaccine inoculation reduces death or culling due to mastitis, whereas no preventive effect on the development of mastitis was observed.

Activated c-Met[pY1003]: A potential marker of intrinsic resistance and therapy target to restore sensitivity to gefitinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7624-7624
Author(s):  
P. A. Zucali ◽  
M. Gallegos Ruiz ◽  
E. Giovannetti ◽  
A. Destro ◽  
K. Floor ◽  
...  
Keyword(s):  
Growth Factor ◽  
Rank Test ◽  
Intrinsic Resistance ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Log Rank Test ◽  
Fisher’S Exact Test ◽  
Nsclc Patients ◽  
Egfr Tkis ◽  
E Cadherin

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.

scholarly journals Contribution of AGTR 1 Promoter Region Polymorphism to the Progression and Outcome of Sepsis in Patients with Various Comorbidities

2021 ◽  
Vol 17 (5) ◽  
pp. 35-51
Author(s):  
A. G. Chumachenko ◽  
E. K. Grigoriev ◽  
V. M. Pisarev
Keyword(s):  
Diabetes Mellitus ◽  
Lower Mortality ◽  
Rank Test ◽  
Functional Polymorphism ◽  
Icu Patients ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Log Rank Test ◽  
Fisher’S Exact Test ◽  
Arteriolar Tone

Blood pressure dysregulation and circulatory failure are major contributors to the progression of sepsis and especially septic shock. One of the genes affecting the vascular endothelium and arteriolar tone is the angiotensin II receptor 1 gene (AGTR1). The AGTR1 rs275651 single-nucleotide polymorphism is associated with the development of angina, high altitude pulmonary edema, and hypertension. The significance of the AGTR1 rs275651 polymorphism in sepsis, particularly in patients with significant comorbidity, has not been studied previously.The aim of the study was to determine the impact of AGTR1 functional polymorphism on sepsis outcome in patients with various comorbidities, including cardiovascular disease and type 2 diabetes mellitus.Material and methods. A prospective study included 144 ICU patients of two clinical hospitals in Moscow, aged 18-75 years with clinical signs of sepsis (Sepsis-3, 2016).Results. In the group of patients with cardiovascular diseases, carriers of the TT AGTR1 rs275651 genotype had a lower mortality rate compared with carriers of the A allele (25 deaths out of 33 versus 16 out of 16, respectively, P=0.041, Fisher's exact test; P=0.0019, log-rank test). In the group of patients with diabetes mellitus (n=62), we also found significant differences in sepsis outcome based on the AGTR1 rs275651 genotype variant. The subgroup of TT AGTR1 rs275651 genotype carriers demonstrated significantly lower mortality compared with TA, AA genotypes carriers (27 deaths out of 41 and 20 out of 21, respectively, P=0.012, Fisher's exact test; OR=10.37; 95% CI: 1.26 to 85.5; P<0.0001, log-rank test).Conclusion. We found an association of the functional polymorphism AGTR1 -777 T>A (rs275651) with sepsis outcome in ICU patients with high-value baseline comorbidity: carriers of the more common TT genotype had lower mortality compared to carriers of the minor A allele.

scholarly journals Detection of AZF microdeletions and reproductive hormonal profile analysis of infertile sudanese men pursuing assisted reproductive approaches

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hassan Osman Alhassan Elsaid ◽  
Tarteel Gadkareim ◽  
Tagwa Abobakr ◽  
Eiman Mubarak ◽  
Mehad A. Abdelrhem ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Klinefelter Syndrome ◽  
Semen Analysis ◽  
Control Group ◽  
Male Factor ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Infertile Men ◽  
Significant Difference ◽  
Fisher’S Exact Test

Abstract Background Male factor is the major contributor in roughly half of infertility cases. Genetic factors account for 10–15% of male infertility. Microdeletions of azoospermia factors (AZF) on the Yq region are the second most frequent spermatogenesis disorder among infertile men after Klinefelter syndrome. We detected in our previous study a frequency of 37.5% AZF microdeletions which investigated mainly the AZFb and AZFc. We attempted in this study for the first time to evaluate the frequencies of all AZF sub-regions microdeletions and to analyze reproductive hormonal profiles in idiopathic cases of azoospermic and oligozoospermic men from Sudan. Methods A group of 51 medically fit infertile men were subjected to semen analysis. Four couples have participated in this study as a control group. Semen analysis was performed according to WHO criteria by professionals at Elsir Abu-Elhassan Fertility Centre where samples have been collected. We detected 12 STSs markers of Y chromosome AZF microdeletions using a multiplex polymerase chain reaction. Analysis of reproductive hormone levels including Follicle Stimulating, Luteinizing, and Prolactin hormones was performed using ELISA. Comparisons between outcome groups were performed using Student’s t-test Chi-square test or Fisher’s exact test. Results AZF microdeletion was identified in 16 out of 25 Azoospermic and 14 out of 26 of the Oligozoospermic. Microdeletion in the AZFa region was the most frequent among the 30 patients (N = 11) followed by AZFc, AZFd (N = 4 for each) and AZFb (N = 3). Among the Oligozoospermic participants, the most frequent deletions detected were in the AZFa region (N = 10 out of 14) and was significantly associated with Oligozoospermic phenotype, Fisher's Exact Test (2-sided) p = 0.009. Among the Azoospermic patients, the deletion of the AZFc region was the most frequent (N = 9 out of 16) and was significantly associated with Azoospermia phenotype Fisher's Exact Test p = 0.026. There was a significant difference in Y chromosome microdeletion frequency between the two groups. The hormonal analysis showed that the mean levels of PRL, LH, and FSH in Azoospermic patients were slightly higher than those in oligozoospermic. A weak negative correlation between prolactin higher level and Azoospermic patients was detected. (AZFa r = 0.665 and 0.602, p = 0.000 and 0.0004, AZFb r = 0.636 and 0.409, p = 0.000 and 0.025, and AZFd r = 0.398 and 0.442, p = 0.029 and 0.015). The correlation was positive for AZFa and negative for AZFb and AZFd. Conclusions We concluded in this study that the incidences of microdeletions of the Y chromosome confined to AZF a, b, c and d regions is 58.8% in infertile subjects with 31.4% were Azoospermic and 27.5% were Oligozoospermic. This might provide a piece of evidence that these specified regions of the Y chromosome are essential for controlling spermatogenesis. These findings will be useful for genetic counseling within infertility clinics in Sudan and to adopt appropriate methods for assisted reproduction.

Επίδραση αναλόγου της προστακυκλίνης στην επούλωση αναστομώσεων του παχέος εντέρου επίμυων σε συνθήκες αποφρακτικού ειλεού

2012 ◽  
Author(s):  
Γεώργιος Γαλανόπουλος
Keyword(s):  
Analysis Of Variance ◽  
Anova Analysis ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Significant Difference ◽  
Fisher’S Exact Test

Στόχος της παρούσας διδακτορικής διατριβής ήταν η πειραματική μελέτη της επίδρασης της ιλοπρόστης (ανάλογο της προστακυκλίνης) στην επούλωση αναστομώσεων του παχέος εντέρου επίμυων σε συνθήκες αποφρακτικού ειλεού. Για τη μελέτη χρησιμοποιήθηκαν 80 άρρενες επίμυες, οι οποίοι χωρίστηκαν τυχαιοποιημένα σε 4 (1, 2, 3, 4) ομάδες, με 2 (α, β) ισοδύναμες υποομάδες έκαστη. Στην ομάδα 1 (ελέγχου) και 3 (ιλοπρόστη) διενεργήθηκε τμηματική εντερεκτομή και τελικοτελική αναστόμωση. Στην ομάδα 2 (ειλεός) και 4 (ειλεός και ιλοπρόστη) επιτεύχθηκαν αρχικά συνθήκες αποφρακτικού ειλεού και 24 ώρες μετά διενεργήθηκε τμηματική εντερεκτομή και τελικοτελική αναστόμωση. Η ιλοπρόστη χορηγήθηκε στις ομάδες 3 και 4 σε δόση 2μg/kg Β.Σ. σε 3ml διαλύματος NaCl 0,9% ενδοπεριτοναϊκά, διεγχειρητικά και κάθε ημέρα μέχρι τη θυσία, ενώ αντίστοιχα στις ομάδες 1 και 2 στα πειραματόζωα χορηγούνταν 3ml διαλύματος NaCl 0,9%. Σε κάθε ομάδα τα μισά πειραματόζωα (υποομάδα 1α, 2α, 3α, 4α) θυσιάστηκαν την 4η μετεγχειρητική ημέρα και τα υπόλοιπα (υποομάδα 1β, 2β, 3β, 4β) την 8η. Κατά τη νεκροτομή γινόταν μακροσκοπικός έλεγχος για ρήξη της αναστόμωσης, ύπαρξη περιτονίτιδος ή περιαναστομωτικού αποστήματος καθώς και ποσοτική αξιολόγηση των συμφύσεων σύμφωνα με την κλίμακα Van der Hamm. Ακολουθούσε μέτρηση της πίεσης διάσπασης και στη συνέχεια τμήμα της αναστόμωσης αποστέλλονταν για ιστολογική εξέταση κατά την οποία αξιολογούνταν η φλεγμονώδης αντίδραση (διήθηση από ουδετερόφιλα), η νεοαγγειογένεση, ο αριθμός των ινοβλαστών και η εναπόθεση νεοκολλαγόνου. Η ταξινόμηση των μικροσκοπικών ευρημάτων έγινε σύμφωνα με την κλίμακα Ehrlich και Hunt με τις τροποποιήσεις κατά Phillips. Επιπλέον, προσδιορίστηκε βιοχημικά η συγκέντρωση υδροξυπρολίνης και κολλαγενάσης I επί της αναστόμωσης. Για την συνοπτική παρουσίαση των αποτελεσμάτων υπολογίστηκαν απόλυτες και σχετικές συχνότητες (ποσοστά %), δείκτες κεντρικής τάσης (μέσοι όροι, διάμεσες τιμές) και δείκτες διασποράς (ελάχιστες τιμές, μέγιστες τιμές, τυπικές αποκλίσεις). Για τη σύγκριση των μέσων όρων χρησιμοποιήθηκε το κριτήριο της Ελάχιστης Σημαντικής Διαφοράς (Least Significant Difference-LSD), μετά από την εφαρμογή της μεθόδου ANOVA (Analysis of Variance). Για τις συγκρίσεις των ποσοστών, εφαρμόστηκε ο ακριβής έλεγχος του Fisher (Fisher’s Exact Test). Από την ανάλυση των πειραματικών δεδομένων προέκυψε ότι η ενδοπεριτοναϊκή χορήγηση ιλοπρόστης σε συνθήκες αποφρακτικού ειλεού, έχει ως αποτέλεσμα τον περιορισμό της αρνητικής δράσης του ειλεού στην επούλωση των αναστομώσεων του παχέος εντέρου. Συγκεκριμένα, την 4η και 8η μετεγχειρητική ημέρα ελαττώνει σημαντικά την απώλεια σωματικού βάρους. Επίσης, προάγει τη νεοαγγειογένεση, ενώ συγχρόνως αυξάνει τον πολλαπλασιασμό των ινοβλαστών και τη συγκέντρωση υδροξυπρολίνης. Επιπλέον, την 4η μετεγχειρητική ημέρα ελαττώνει τη φλεγμονώδη αντίδραση και μειώνει τη συγκέντρωση κολλαγενάσης Ι. Σταδιακά, την 8η μετεγχειρητική ημέρα αυξάνει τη σύνθεση νεοκολλαγόνου στην περιοχή της αναστόμωσης. Οι παραπάνω δράσεις έχουν ως αποτέλεσμα την αύξηση της μηχανικής ισχύος των αναστομώσεων, κατά την 4η και 8η μετεγχειρητική ημέρα, όπως αυτή προκύπτει από τη μέτρηση των πιέσεων διάσπασης. Συμπερασματικά, η άμεση μετεγχειρητική ενδοπεριτοναϊκή χορήγηση ιλοπρόστης ενισχύει τους μηχανισμούς επούλωσης και αντισταθμίζει την αρνητική δράση του ειλεού στην επούλωση των αναστομώσεων του παχέος εντέρου.

scholarly journals The yield of colorectal cancer among fast track patients with normocytic and microcytic anaemia

2014 ◽  
Vol 96 (4) ◽  
pp. 289-293 ◽  
Author(s):  
IG Panagiotopoulou ◽  
D Fitzrol ◽  
RA Parker ◽  
J Kuzhively ◽  
N Luscombe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Logistic Regression ◽  
Odds Ratio ◽  
Fast Track ◽  
Microcytic Anaemia ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Significant Difference ◽  
Fisher’S Exact Test ◽  
Normocytic Anaemia

Introduction We receive fast track referrals on the basis of iron deficiency anaemia (IDA) for patients with normocytic anaemia or for patients with no iron studies. This study examined the yield of colorectal cancer (CRC) among fast track patients to ascertain whether awaiting confirmation of IDA is necessary prior to performing bowel investigations. Methods A review was undertaken of 321 and 930 consecutive fast track referrals from Centre A and Centre B respectively. Contingency tables were analysed using Fisher’s exact test. Logistic regression analyses were performed to investigate significant predictors of CRC. Results Overall, 229 patients were included from Centre A and 689 from Centre B. The odds ratio for microcytic anaemia versus normocytic anaemia in the outcome of CRC was 1.3 (95% confidence interval [CI]: 0.5–3.9) for Centre A and 1.6 (95% CI: 0.8–3.3) for Centre B. In a logistic regression analysis (Centre B only), no significant difference in CRC rates was seen between microcytic and normocytic anaemia (adjusted odds ratio: 1.9, 95% CI: 0.9–3.9). There was no statistically significant difference in the yield of CRC between microcytic and normocytic anaemia (p=0.515, Fisher’s exact test) in patients with anaemia only and no colorectal symptoms. Finally, CRC cases were seen in both microcytic and normocytic groups with or without low ferritin. Conclusions There is no significant difference in the yield of CRC between fast track patients with microcytic and normocytic anaemia. This study provides insufficient evidence to support awaiting confirmation of IDA in fast track patients with normocytic anaemia prior to requesting bowel investigations.

scholarly journals ζ-, ε-, and γ-Globin mRNA in Blood Samples and CD71+ Cell Fractions from Fetuses and from Pregnant and Nonpregnant Women, with Special Attention to Identification of Fetal Erythroblasts

2001 ◽  
Vol 47 (4) ◽  
pp. 645-653 ◽  
Author(s):  
Anne Mette Høgh ◽  
Thomas Vauvert F Hviid ◽  
Britta Christensen ◽  
Steen Sørensen ◽  
Rasmus D Larsen ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Rt Pcr ◽  
Globin Mrna ◽  
Isolation And Identification ◽  
Blood Samples ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Significant Difference ◽  
Fisher’S Exact Test ◽  
Cell Fractions

Abstract Background: Information about the appearance of γ-, ε-, and ζ-globin mRNAs in fetal erythroblasts during gestation and about the presence and amounts of these mRNAs in pregnant and nonpregnant women is important from the perspective of using these molecules as a marker of fetal erythroblasts. A specific marker is necessary for isolation and identification of fetal nucleated red blood cells from maternal blood samples for use in antenatal diagnosis of fetal genetic or chromosomal abnormalities. Methods: We used a very sensitive reverse transcription-PCR (RT-PCR) method, coamplification analysis of γ- and ε-globin cDNA, and quantitative analysis of γ-globin mRNA based on competitive RT-PCR to investigate these aspects. Results: All adult whole-blood samples were negative for ε- and ζ-globin mRNA. Analyses of CD71+ cell fractions showed that specimens from 19 of 20 nonpregnant and 10 of 14 pregnant women (at 9–13 weeks of gestation) were positive for γ-globin mRNA (Fisher’s exact test, P = 0.13), and those from 3 of 20 nonpregnant and 5 of 14 pregnant women were positive for ζ-globin mRNA (Fisher’s exact test, P = 0.23). No ε-globin mRNA was detected in CD71+ cell fractions from 1-mL blood samples from adults. CD71+ cell fractions from eight fetal blood samples (at 17–20 weeks of gestation) were positive for all three globin mRNAs. We found no statistically significant difference between the amounts of γ-globin mRNA in pregnant and nonpregnant women. Conclusions: This study indicates that ε-globin mRNA might function as a marker for fetal CD71+ cells early in pregnancy. Although γ-globin mRNA can be detected in CD71+ cell fractions from most adults, these transcripts also may be of use because of a marked difference between adult and fetal values.

scholarly journals TLR4 T399I Polymorphism and Endometriosis in a Cohort of Italian Women

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 255 ◽  
Author(s):  
Enrica Marchionni ◽  
Maria Grazia Porpora ◽  
Francesca Megiorni ◽  
Ilaria Piacenti ◽  
Agnese Giovannetti ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Categorical Variables ◽  
P Value ◽  
Genotype Distribution ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
Fisher’S Exact Test ◽  
Italian Women

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.

Expression of Inhibitory Fc Receptor (FcγRIIB) Is a Marker of Poor Response to Rituximab Monotherapy in Follicular Lymphoma (FL).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2747-2747
Author(s):  
Chern Siang Lee ◽  
Margaret Ashton-Key ◽  
Sergio Cogliatti ◽  
Susanne Crowe ◽  
Mark S Cragg ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Single Agent ◽  
Poor Response ◽  
Prolonged Treatment ◽  
Induction Treatment ◽  
Type Ii ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Significant Difference ◽  
Fisher’S Exact Test

Abstract Abstract 2747 Background: Single-agent immunotherapy with rituximab is a viable treatment option for low risk FL, with limited toxicity and a long duration of response in some patient subsets. We have previously shown that high expression of FcγRIIB promotes rituximab internalisation on various B cell targets, including FL (Blood 2011 118:2530–2540), something not seen with type II anti-CD20 antibodies. The SAKK 35/98 trial examined rituximab monotherapy in FL and now has long-term follow-up data of almost 10 years (JCO 2010 28:4480–4484). We analysed diagnostic tumour samples from this trial to determine the relationship of FcγRIIB expression to responses and clinical outcomes after rituximab treatment in FL. Methods: 202 patients (pts) with newly diagnosed or relapsed FL received induction treatment with rituximab 375 mg/m2 weekly for 4 weeks. Pts with stable or responding disease at week 12 were randomized into 2 groups: no further treatment or prolonged treatment with single infusions of rituximab 375 mg/m2 at weeks 12, 20, 28 and 36. Archived tissue samples from 135 evaluable pts were stained using an anti-human FcγRIIB antibody (clone EP888Y, Abcam) at a dilution of 1:3000 on a Dako autostainer. The samples were pretreated with the Dako EnVisionFLEX target retrieval solution high pH and detection using the Dako AS-Link 48 with Dako EnVision flex plus detection kit. Positive samples were graded into negative/low intensity staining (n=120) versus medium/high (n=13) by an expert lymphoma histopathologist blinded to the clinical outcomes. Data from 2 slides and response at week 12 data for 4 pts were unavailable (1 of whom also has missing slide data), resulting in 130 pts available for analysis. Failure-free survival (FFS) was defined as time from registration until failure to achieve complete/partial response at week 12, progression, relapse, a second cancer or death from any cause. Objective response rate (ORR) was associated with intensity staining levels using Fisher's exact test. All time-to-event endpoints were evaluated using the Kaplan-Meier method; groups were compared using the log-rank test. The hazard ratio (HR) was assessed using Cox proportional hazards models. Results: Registered and randomised pts had very similar baseline characteristics; previously untreated pts had slightly more favourable characteristics but were balanced between the 2 treatment arms. Pts expressing medium/high levels of FcγRIIB were less likely to respond to rituximab by week 12 (ORR 58.1% vs 23.1%, Fisher's exact test, p=0. 02), a finding independent of prior therapy. For FFS, there was a statistically significant difference (p=0.001; HR=0.42; 95% confidence interval (C.I.): 0.23–0.77) between the negative/low staining group (median: 21.4 months; 95% C.I.: 7.0–34.2) and the medium/high staining group (median: 7.0 months; 95% C.I.: Not calculable). The interaction between staining levels and randomised treatment groups for FFS was not statistically significant. There was a non-significant trend towards better overall survival in the low/negative group (median: 140.0 vs 50.0 months; p=0.15; HR=0.57; 95% C.I.: 0.27–1.23); however the event rate was lower (36.8% vs 61.5%). Conclusion: Elevated FcγRIIB expression level is associated with poor response to rituximab in pts with FL. This group may show better results with non-internalising type II antibodies, a hypothesis for validation in future prospective clinical trials. Disclosures: Ghielmini: Roche: Honoraria, Speakers Bureau. Johnson:Roche: Honoraria.

Effects on histologic subgroup, race, and BMI in 2,110 breast cancer patient: Results from single institution in Georgia.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13112-e13112
Author(s):  
Ricardo H. Alvarez ◽  
Rebecca Rollins ◽  
Joe Ensor ◽  
Daniel W. Nixon ◽  
Jonathan Ramey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Breast Cancer Mortality ◽  
Population Based ◽  
Rank Test ◽  
Racial Groups ◽  
Single Institution ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test

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]

STK11/LKB1 co-mutations to predict for de novo resistance to PD-1/PD-L1 axis blockade in KRAS-mutant lung adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9016-9016 ◽  
Author(s):  
Ferdinandos Skoulidis ◽  
Matthew David Hellmann ◽  
Mark M. Awad ◽  
Hira Rizvi ◽  
Brett W. Carter ◽  
...  
Keyword(s):  
De Novo ◽  
Therapeutic Potential ◽  
Immune Checkpoint Blockade ◽  
Rank Test ◽  
Causative Role ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Predictors Of Response ◽  
Fisher’S Exact Test ◽  
De Novo Resistance

9016 Background: Identification of molecular predictors of response to PD-1/PD-L1 inhibitors is critical in order to maximize their therapeutic potential. We previously reported that KRAS-mutant lung adenocarcinomas (LUAC) with co-occurring genetic events in STK11/LKB1(KL) or TP53 (KP) define subgroups with marked differences in immune contexture, including a paucity of CD8+ TILs in KL LUAC. Here, we assess clinical responses to PD-1/PD-L1 therapy in KL and KP subsets, with data assembled under the auspices of the SU2C/ACS Lung Cancer Dream Team. Methods: Patients (pts) with metastatic KRAS-mutant LUAC who received at least one cycle of PD-1/PD-L1 therapy, were alive for ≥14 days thereafter, and had available molecular profiling were identified retrospectively. Efficacy assessment was based on RECIST v1.1. PD-L1 expression was tested using 22C3 pharmDx or E1L3N IHC assays and quantified as percent of staining tumor cell membranes. Isogenic derivatives of the LKR10 KrasLA1/+ murine LUAC cell line with CRISPR/Cas9-mediated Lkb1knockout were used in preclinical experiments. Results: 165 pts with KRAS-mutant LUAC who received PD-1/PD-L1 therapy were included [KL: 27%, KP: 36%, K-only: 37%]. Best overall response differed significantly in the KL (PR: 9.1%, SD: 15.9%, PD: 75%) and KP (PR: 33.3%, SD: 20%, PD: 46.7%) sub-groups (P = 0.005, Fisher’s exact test). PFS was significantly longer in KP compared to KL LUAC (median 12.9 wks vs 8.4 wks, HR = 0.64, 95% CI 0.39-0.95, P = 0.032, log-rank test). ORR in K-only tumors was 21.3% and median PFS 11.4 wks. PD-L1 positivity (≥1%) was more frequent in KP tumors compared to KL (75% vs 22%, P = 0.03, Fisher’s exact test). In syngeneic murine models of KRAS-mutant LUAC, loss of LKB1 promoted resistance to PD-1 inhibitor monotherapy, suggesting a causative role. Conclusions: Mutational inactivation of STK11/LKB1 represents a novel genomic predictor of de novo resistance to immune checkpoint blockade in KRAS-mutant LUAC, whereas TP53 co-mutations are associated with high likelihood of response. Precision immunotherapy will require tailoring to the co-mutation status of individual tumors.

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