P–305 The expression of innate immune factors in the eutopic endometrium of women with endometriosis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Reidy ◽  
F Giangrazi ◽  
C O’Farrelly ◽  
M Wingfield ◽  
L Glover
Keyword(s):  
Antimicrobial Peptides ◽  
Innate Immune ◽  
Disease Stage ◽  
Pcr Analysis ◽  
Cycle Phase ◽  
Eutopic Endometrium ◽  
Protein Levels ◽  
Significant Difference ◽  
Endometrial Scratch ◽  
The Impact

Abstract Study question Is the expression of IL–17A and antimicrobial peptides (AMPs) altered in endometriosis? Summary answer IL–17A protein levels were similar in the endometrium of women with and without endometriosis but the expression of several AMPs was reduced in endometriosis. What is known already Chronic inflammation and aberrant immune signalling in the eutopic endometrium underlies the pathophysiology of endometriosis. Endometrial IL–17 levels have previously been shown by our group to be negatively correlated with successful pregnancy. IL–17 has also been associated with endometriosis. Among its immunomodulatory functions, IL–17 regulates the expression of several antimicrobial peptides (AMPs), highly conserved proteins that are involved in the innate immune response. Despite the well accepted paradigm of immune dysregulation in endometriosis, surprisingly little is known about the relationship between endometrial IL–17, AMPs and endometriosis, particularly in the context of infertility. Study design, size, duration This was a prospective cohort study. Endometrial biopsy samples were collected at the time of endometrial scratch testing, or during elective laparoscopy, over a 15-month period. The aim was to evaluate and compare IL–17A protein levels and the expression of specific AMPs (SLPI, elafin, beta-defensin 1, S100A7, S100A8, S100A9) [MW1] , in the endometrium of patients with endometriosis, and those without the disease. Participants/materials, setting, methods Thirty-two patients were recruited for the study, with 26 included in the final analysis. Biopsies were obtained at the time of planned endometrial scratch (mid-luteal phase) prior to ART (n = 7), or at the time of laparoscopy (n = 19). RNA was extracted and Q-PCR analysis for AMP transcript levels was performed. ELISA was carried out to quantify levels of IL–17A in endometrial tissue in a subgroup (n = 17). Main results and the role of chance: In our cohort IL–17A protein levels were not significantly different in the endometrium of patients with disease compared to those without (p = 0.3636). The expression of the AMPs elafin, SLPI, BD1 and S100A9, as measured by a Q-PCR transcript profiling approach, were found to be significantly reduced in the eutopic endometrium in cases of endometriosis as compared to cases without endometriosis. There was no significant difference in AMP expression between disease stages. No demonstrable difference in IL–17A protein levels, or AMP expression was detected between the proliferative and secretory phases of the menstrual cycle. Limitations, reasons for caution Numbers may not have been large enough to fully evaluate the impact of endometriosis stage or the effect of cycle phase. While all patients with endometriosis had surgical confirmation of disease, not all patients in the control cohort had a laparoscopy, though they had no clinical features suggestive of endometriosis. Wider implications of the findings: Our findings indicate that the innate immune environment of the eutopic endometrium is altered in endometriosis. Endometrial expression of AMPs was diminished in endometriosis, independent of disease stage. This work supports the model of dysregulated innate immune system in endometriosis, and reveals AMPs as novel immune players in disease pathogenesis. Trial registration number Not applicable

scholarly journals Antimicrobial peptides in patients with anorexia nervosa: comparison with healthy controls and the impact of weight gain

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marie-Christin Bendix ◽  
Michael Stephan ◽  
Mariel Nöhre ◽  
Wally Wünsch-Leiteritz ◽  
Hagen Schmidt ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Weight Gain ◽  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Innate Immune ◽  
Effect Sizes ◽  
Healthy Controls ◽  
Clinical Observations ◽  
The Impact

AbstractClinical observations show that patients with anorexia nervosa (AN) are surprisingly free from infectious diseases. There is evidence from studies in Drosophila melanogaster that starvation leads to an increased expression of antimicrobial peptides (AMPs). AMPs are part of the innate immune system and protect human surfaces from colonization with pathogenic bacteria, viruses and fungi. We compared the expression of AMPs between patients with AN and healthy controls (HC) and investigated the influence of weight gain. Using a standardized skin rinsing method, quantitative determination of the AMPs psoriasin and RNase 7 was carried out by ELISA. Even though non-significant, effect sizes revealed slightly higher AMP concentrations in HC. After a mean weight gain of 2.0 body mass index points, the concentration of psoriasin on the forehead of patients with AN increased significantly. We could not confirm our hypotheses of higher AMP concentrations in patients with AN that decrease after weight gain. On the contrary, weight gain seems to be associated with increasing AMP concentrations.

Use of Pre-Emptive Donor Lymphocyte Infusions To Achieve Durable Remission Following Alemtuzumab Based Reduced Intensity Conditioning (RIC) Transplantation for AML or MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1124-1124
Author(s):  
ZiYi Lim ◽  
Laurence Pearce ◽  
Wendy Ingram ◽  
Rafael Duarte ◽  
Stephen Devereux ◽  
...  
Keyword(s):  
T Cell ◽  
Advanced Disease ◽  
Disease Stage ◽  
Mixed Chimerism ◽  
Donor Chimerism ◽  
Significant Difference ◽  
Cell Source ◽  
Recipient Age ◽  
The Impact

Abstract Use of alemtuzumab in RIC HSCT reduces the incidence of graft rejection and graft vs host disease(GvHD). However, there can be a delay in full T-cell donor engraftment. As a dominant donor T-cell chimerism may be important to achieve a strong graft vs leukaemia effect(GvL), we examined the impact of pre-emptive DLI (pDLI) on patients with falling donor chimerism. 76 patients with AML or MDS were treated with RIC HSCT (fludarabine 150mg/m2, busulphan 8mg/kg, alemtuzumab 100mg). Complete sublineage chimerism data up to day +100 was available on all patients. The underlying diagnoses were AML n=27, MDS n=49. 33 patients had early disease vs 44 advanced disease (advanced disease as defined by AML >CR1, MDS RAEB or AML with multilineage dysplasia). The median recipient age was 51.6 years (range:19–72), with median follow-up of 526 days (range:137–1256). There were 30 sibling and 50 VUD allografts. Stem cell source was 61 PBSC vs 15 BM. 62 patients were fully HLA matched and 14 patients were HLA mismatched. CD15 engraftment occurred rapidly with 95% of patients achieving full donor chimerism(FDC) at day 30 and 96% at day 100. In contrast, CD3 engraftment was significantly delayed, with only 50% of patients FDC at day 30, 47% at day 100. Incremental doses of pDLI were considered for patients with falling donor chimerism (<50% donor) after day 100. Patients had immunosuppresion withdrawn, and had to have no GvHD. 20 patients received a total of 55 doses of pDLI. 10/20 had advanced disease, and 6/20 had unfavourable cytogenetics. Median donor CD3 chimerism at time of pDLI was 31.5%(range:7–59). The median CD3 dose of pDLI was 8.4x106/kg, with the first dose given at a median of day +176 (range:104–494). The median interval between pDLI was 8 weeks(range:4–22). 15 patients had FDC restored at median of 130 days following first doses of pDLI (range:36–523). 8/20 developed acute Gd II-IV GvHD following pDLI, with 2 patients dying of GvHD related complications. 2 patients relapsed with AML following treatment: with 1 death, and 1 patient currently undergoing treatment. 2 patients had not reached FDC at follow-up. A further 9 patients received DLI for cytogenetic or morphological relapse. Time to first dose of DLI was 257 days (range:76–837). The median CD3 dose was 1.67 x 107/kg. 3 patients were FDC and 6 patients MDC at time of relapse. All 3 patients with FDC failed to respond to DLI. Complete remission was seen in 3/6 patients with MDC. 4/9 patients developed acute Gd II-IV GvHD. 5/9 patients have died(all of underlying AML). The outcome of patients receiving pDLI was compared with patients with FDC(n=28), and stable mixed chimerism(defined as donor CD3 chimerism >70%) who did not receive DLI(n=18). There was no significant difference in recipient age, disease, disease stage, HLA type, cell source or cell dose between groups. However, there were more sibling donors in the group receiving pDLI(p=0.02). The 2 year DFS, OS and relapse rate was comparable between patients with FDC, stable chimerism and those receiving pDLI (59% vs 83% vs 67% p=0.22), (62% vs 88% vs 75% p=0.13), (12% vs 17% vs 15% p=0.74) respectively. In summary, pre-emptive DLI is effective in reversing falling donor chimerism, and can induce prolonged remission, even in a sub-group of patients with high risk disease. A dominant donor CD3 chimerism(>70%) may be sufficient to acheive an allo-immune effect in majority of patients.

scholarly journals Does Addition of Rituximab (R) to BEAM Conditioning Improve Outcomes of Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Autologous Hematopoietic Cell Transplantation (auto-HCT)?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 785-785
Author(s):  
Deepa Jagadeesh ◽  
Navneet S. Majhail ◽  
He Yizeng ◽  
Kwang Woo Ahn ◽  
Carlos Litovich ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Older Age ◽  
Disease Stage ◽  
Karnofsky Performance Score ◽  
Advisory Committees ◽  
Significant Difference ◽  
The Impact

Introduction: Rituximab-based high-dose therapy (HDT) is frequently prescribed to DLBCL patients (pts) undergoing auto-HCT. However data supporting the benefit of adding R to auto-HCT conditioning are not available. Herein, we report the impact of R-based conditioning on auto-HCT outcomes of DLBCL pts. Methods: Using the Center for International Blood and Marrow Transplant Research registry, 862 adult (≥18 years) DLBCL pts undergoing auto-HCT, between 2003-2017 were included. Analysis was limited to pts receiving BEAM (BCNU, etoposide, cytarabine, melphalan)-based HDT, as R was infrequently used with non-BEAM conditioning regimens. All pts received R-containing chemoimmunotherapy in the frontline setting and had chemosensitive disease prior to HCT. Early chemoimmunotherapy failure (ECitF) was defined as not achieving a complete remission (CR) after frontline chemoimmunotherapy or relapsing within 1 year of initial diagnosis. Primary outcome was overall survival (OS). Secondary outcomes included non-relapse mortality (NRM), relapse, progression-free survival (PFS) and infectious complications within 100 days post-HCT. Results: The study cohort was divided into 2 groups; BEAM (n=667) and R-BEAM (n=195). The baseline characteristics of the 2 cohorts were comparable including age at auto-HCT, disease stage, Karnofsky performance score, extranodal involvement, time from diagnosis to auto-HCT, number of prior therapies, remission status, and ECitF. However, significantly more R-BEAM cohort patients received R as part of last therapy line before auto-HCT (75% vs. 86%; P=0.001). Median follow-up of survivors was 48 (range 1-171) and 64 (range 3-142) months in the BEAM and R-BEAM cohorts, respectively. On univariate analysis, the 4 year cumulative incidence of relapse (41% vs 44%), NRM (11% vs 9%), PFS (48% vs 47%; Figure 1) and OS (58% vs 61%; Figure 2) were similar in the R-BEAM and BEAM groups, respectively (Table 1). On multivariate analysis, no significant difference was seen in OS (HR 0.81; 95% CI 0.81-1.31; P=0.83) or PFS (HR 0.94; 95% CI 0.76-1.18; P=0.61) (Table 1) between the two cohorts. Addition of R had no impact on risk of relapse (HR 0.83; 95% CI 0.65-1.07; P=0.15) or NRM (HR 1.43; 95% CI 0.909-2.26; P=0.12). Variables independently associated with lower OS included older age (HR 3.05; 95% CI 1.81-5.13; P<0.001), not being in CR at auto-HCT (HR 1.67, 95% CI 1.39-2.07; P<0.001) and presence of ECitF (HR 1.52, 95% CI 0.54-3.26; P<0.001). Older age (HR 2.26, 95% CI 1.48-3.45; P<0.0002) and not being in CR at auto-HCT (HR 1.78, CI 1.47-2.14; P<0.0001) were also associated with inferior PFS. There was no significant difference in the 100-day cumulative incidence of bacterial, viral or fungal infections between the two cohorts. Disease relapse was the main cause of death in both BEAM and R-BEAM cohorts (66% vs 55%). Conclusion: In this large registry analysis of DLBCL pts undergoing auto-HCT, adding R to BEAM conditioning had no impact on transplantation outcomes. Older age, absence of CR and ECitF were associated with inferior survival. Disclosures Majhail: Mallinckrodt: Honoraria; Incyte: Consultancy; Nkarta: Consultancy; Anthem, Inc.: Consultancy; Atara Bio: Consultancy. Sureda:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Gilead: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria; BMS: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Hamadani:ADC Therapeutics: Consultancy, Research Funding; Merck: Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy; Celgene: Consultancy; Medimmune: Consultancy, Research Funding; Janssen: Consultancy; Otsuka: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau.

Matched Pair Analysis of Intravenous vs Oral Busulphan as Part of Fludarabine-Busulphan-Campath (Alemtuzumab) Reduced Intensity Conditioning (RIC) Haematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1762-1762
Author(s):  
ZiYi Lim ◽  
Dragana Milojkovic ◽  
Laurence Pearce ◽  
Michelle Kenyon ◽  
Aloysius Ho ◽  
...  
Keyword(s):  
Previous History ◽  
Disease Free Survival ◽  
Disease Stage ◽  
Haematopoietic Stem Cell ◽  
Matched Pair ◽  
Donor Chimerism ◽  
Matched Pair Analysis ◽  
Significant Difference ◽  
Oral Group ◽  
The Impact

Abstract The use of IV busulphan (Bu) has reported improved bioavailability with lower variability of plasma levels, and may reduce the incidence of hepatic veno-occlusive disease (HVOD) and lower the transplant related toxicity. We performed a retrospective matched 2:1 case analysis to evaluate the impact of the use of oral vs IV busulphan as part of RIC HSCT on toxicity as well as engraftment. 75 patients received fludarabine (30mg/m2 x 5 days), alemtuzumab (20mg x 5 days) and either oral Bu (4mg/kg x 2 days) (25 patients) or IV Bu (3.2mg/kg x 2 days) (50 patients). 25 patients received IV Bu between Jan 2004 and Jan 2005. Each of these patients was matched for sex, diagnosis, disease stage, donor status and cell source with 2 comparable historical patients receiving oral Bu. There were 42 male and 33 female patients. Median age was 55 years (range:22–72). Median follow-up was 850 days (range: 39–1820) for the oral Bu group and 228 days (range: 38–453) for the IV Bu group. All patients were being treated for myeloid malignancies: AML n=21, MDS/MPD n=45, CML n= 9. There were 33 sibling matched HSCT, 27 matched VUD HSCT and 15 HLA-mismatched VUD HSCT. 63 patients received PBSC and 12 received BM, the median CD34 cell dose was 5.17 x 106/kg (range:1.2–18.5) and 2.49 x 106/kg (range:0.7–4.9) respectively. 28 patients had early disease vs 48 advanced disease (advance disease defined as AML > CR1, CML > CP1, MDS with RAEB or AML with multilineage dysplasia). 5 patients in the oral group and 3 patients in the IV group had a previous allogenic HSCT. No patients had a previous history of hepatic impairment. Median time to neutrophil (>0.5x10^9/kg) and platelet (>20x10^9/kg) regeneration was 12 days and 14 days respectively, with no significant difference between both arms. There was 1 case of primary graft failure and 1 case of HVOD in both arms. Both patients with HVOD had a previous allogeneic HSCT. Myeloid (CD15) engraftment occurred rapidly in both groups with full donor chimerism (>95% donor chimerism) achieved at day+28/day+100/day+180 in 92%/90%/86% IV and 90%/85%/89% oral Bu patients. Lymphoid (CD3) engraftment was delayed in both groups, with full donor chimerism in 28%/26%/37% of IV Bu and 56%/57%/49% of oral Bu patients at day+28/day+100/day+180. 14 patients in the oral Bu group had grade I–III acute graft versus host disease (aGvHD), of which 3 had Gd III aGvHD. In contrast, 4 patients in the IV Bu group developed Gd I–III aGvHD, with 1 patient having Gd III aGvHD. The day +100 treatment related mortality (TRM100) was 8% in both groups. The overall survival (OS), disease free survival (DFS) and relapse incidence at day +200 for the IV vs oral groups was (86% vs 70%, p=0.30), (75% vs 60%, p=0.21), and (18% vs 24%, p=0.36) respectively. In summary, RIC HSCT with both oral and IV busulphan appears to be safe and well tolerated regimen with a low incidence of HVOD and low TRM100. Persisting CD3 mixed donor chimerism is seen in both arms, with a trend to lower incidence of aGvHD with IV Bu (p=0.09) with no significant difference in early relapse, DFS, OS.

scholarly journals The Impact of GPIba on the Efficacy of Platelet-Targeted FVIII Gene Therapy in Hemophilia a with Pre-Existing Anti-FVIII Immunity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1067-1067
Author(s):  
Juan Chen ◽  
Jocelyn Schroeder ◽  
Xiaofeng Luo ◽  
Robert R Montgomery ◽  
Qizhen Shi
Keyword(s):  
Gene Therapy ◽  
Clinical Efficacy ◽  
Hemophilia A ◽  
Hemoglobin Level ◽  
Pcr Analysis ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Model Control ◽  
Significant Difference ◽  
The Impact

Abstract Platelets play fundamental roles in hemostasis through surface proteins, e.g. GPIb, and storage proteins, such as von Willebrand factor (VWF). Our previous studies have demonstrated that FVIII ectopically targeted to platelets under control of the platelet-specific aIIb promoter (2bF8) is therapeutic in hemophilia A mice even in the presence of anti-FVIII inhibitory antibodies (inhibitors). Our recent studies have shown that VWF is essential in platelet-targeted FVIII gene therapy of hemophilia A with inhibitors. Without VWF, the clinical efficacy of platelet-FVIII was aborted. In primary hemostasis, platelets adhere to the vessel wall through the binding of GPIb to VWF. Thus, we wanted to explore whether GPIb is critical for maintaining the clinical efficacy of platelet-FVIII gene therapy of hemophilia A in the presence of inhibitors. To address this question, recipient FVIIInull (F8null) mice were immunized with recombinant FVIII (rhF8) to induce anti-FVIII inhibitory antibody development (the inhibitor model). Hematopoietic stem cells (HSCs) from GPIba knockout (Ibnull) mice were transduced with 2bF8 lentivirus and transplanted into rhF8-primed F8null mice under 1100 cGy total body irradiation (2bF8-Ibnull/F8null). As an inhibitor model control (2bF8-F8null/F8null), HSCs from F8null mice were transduced with 2bF8 and transplanted into rhF8-primed recipients under the same preconditioning. After bone marrow transplantation and reconstitution, animals were assessed for transgene expression and phenotypic correction. PCR analysis showed that the 2bF8 transgene was detected in all of the transduced recipients, demonstrating the viability of 2bF8-transduced engraftment. The level of functional platelet-FVIII expression as determined by a Chromogenic assay was 6.37 ± 5.62 mU/108 platelets (n = 6), which appeared to be higher than the level obtained in the inhibitor control group (1.97 ± 0.96 mU/108 platelets, n = 5), but there was no significant difference between these two groups. Since the size of Ibnull platelets is larger and the platelet number is lower than those in F8null mice, we converted FVIII levels into mU/ml whole blood and the level was 10.36 ± 5.33 mU/ml in 2bF8-Ibnull/F8null mice, which is not significantly different from the 2bF8-F8null/F8null mice (9.04 ± 3.38 mU/ml). When the tail bleeding test was used to grade phenotypic correction of the F8null coagulation defect, all transduced recipients in both groups survived beyond a 6-hour tail clipping test and the remaining hemoglobin level in the 2bF8-Ibnull/ F8null group was 46.4 ± 8.5%, which is not significantly different from the 2bF8-F8null/F8null group (48.3 ± 9.7%). The remaining hemoglobin levels in both groups were significantly higher than in the untransduced F8null control, in which only 5 of 12 animals survived beyond the 6-hour tail clipping test with a remaining hemoglobin level of 34.8 ± 7%. Thus, our data suggest that a lack of platelet GPIba does not negate the clinical efficacy of platelet FVIII gene therapy in hemophilia A in the presence of inhibitors. Disclosures Montgomery: Baxter: Consultancy; Bayer: Consultancy; CSL: Consultancy; Biogen: Consultancy; Octapharma: Consultancy; Grifols: Consultancy. Shi:BloodCenter of Wisconsin: Patents & Royalties: METHOD OF INDUCING IMMUNE TOLERANCE THROUGH TARGETTED GENE EXPRESSION..

144 Sex ratio of in vitro-produced goat embryos

2019 ◽  
Vol 31 (1) ◽  
pp. 197 ◽  
Author(s):  
M. Stoltzfus ◽  
J. Wayman ◽  
R. Stilz ◽  
D. Bresnahan
Keyword(s):  
Sex Ratio ◽  
Dna Extraction ◽  
Culture Media ◽  
The United States ◽  
Blastocyst Stage ◽  
Culture Conditions ◽  
Pcr Analysis ◽  
Significant Difference ◽  
The Impact

Goats are important livestock species because they produce meat, milk, and fibre and are also easily maintainable on small farms. Although goats provide many products and consumption of goat meat is increasing in the United States, the industry lags compared with many species with regard to IVF techniques to enhance goat production. It has been demonstrated in other species that male IVF embryos tend to develop faster than those of females. This may be due to increased tolerance of male embryos to inadequate conditions, particularly, glucose concentrations in culture media. However, the sex ratio of goat embryos produced utilising IVF remains unknown. The aim of this study was to determine the sex ratio of goat embryos utilising a commercially available media suite (IVF Biosciences, Falmouth, UK). Oocytes were harvested from ovaries obtained from 2 local abattoirs and matured in vitro. Frozen sperm from 1 of 2 billy goats were randomly assigned for each round of IVF. Embryos were evaluated daily from Days (D) 6 through 9 of in vitro culture. On the day an embryo reached the expanded blastocyst stage, it was removed from culture and placed into DNA extraction buffer (PicoPureTM DNA Extraction Kit, Applied Biosystems, Waltham, MA, USA) and stored at −20 for PCR analysis, typically within one month of collection. In all unknown samples, positive male (sperm) and female (uterus) controls, the amelogenin gene was amplified and products were evaluated on a 1.5% agarose gel with ethidium bromide. Embryos with 2 bands (202 and 262bp) were classified as male, and those with 1 band (262bp) were classified as female. Embryos with no bands were not included in analysis. Embryos reached the expanded blastocyst stage on D6 (n=29), D7 (n=39), and D8/9 (n=35, combined for evaluation). A chi-squared analysis comparing the percentage of male and female embryos to the expected 50% was completed for each time point (D6, D7, D8/9), as well as overall ratios (D6-9). In total, 350 oocytes were utilised in 6 rounds of IVF resulting in a mean blastocyst rate of 32% (range 17-47%). There was no significant difference in the number of embryos that were male on D6 (55%) and D7 (46%). However, on D8/9 significantly fewer embryos were male (29% male; P=0.01). Overall, there was no significant difference (P=0.14) in the sex ratio, with 41% male and 59% female embryos. Our findings are somewhat consistent with other species, in that male goat embryos produced via IVF develop more quickly in culture conditions; however, female embryos were still able to tolerate culture conditions. Delayed blastocyst development may not necessarily be an indication of a reduced quality embryo but one that is slower to develop based on its sex. This could be due to expression of X-linked genes being unbalanced during pre-implantation embryo development stages and warrants further study. One influencer of sex ratio we are currently investigating is the impact of glucose during culture, to further understand metabolism in IVF embryos.

Neoadjuvant Chemotherapy Is Associated With Prolonged Primary Treatment Intervals in Patients With Advanced Epithelial Ovarian Cancer

2011 ◽  
Vol 21 (1) ◽  
pp. 66-71 ◽  
Author(s):  
Michael R. Milam ◽  
Xia Tao ◽  
Robert L. Coleman ◽  
Robyn Harrell ◽  
Roland Bassett ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Disease Stage ◽  
Perioperative Outcomes ◽  
Cycle Number ◽  
Significant Difference ◽  
Advanced Epithelial Ovarian Cancer ◽  
The Impact

Background:We evaluated the impact of neoadjuvant chemotherapy (NC) relative to primary surgery (PS) to determine if there was a difference in the total time and number of chemotherapy cycles given in patients with advanced epithelial ovarian cancer.Methods:We identified 263 consecutive women meeting eligibility from 1993 to 2005 for this institutional review board-approved study. Eligible patients in this analysis were those women with advanced disease (stage IIIC-IV) in whom a maximal cytoreductive effort was planned either at PS or after NC. Time to start chemotherapy was defined as follows: (1) NC group: confirmation of diagnosis through biopsy, cytological diagnosis from ascites, and pleural effusion; (2) PS group: confirmation of diagnosis from the date of surgery that confirmed the diagnosis of epithelial ovarian cancer. Total chemotherapy cycles: (1) NC group: NC chemotherapy cycles plus postoperative cycles; (2) PS group: chemotherapy after primary tumor debulking surgery. Clinical information evaluated included chemotherapy type, chemotherapy cycle number, total time to administer frontline chemotherapy, and survival.Results:Median chemotherapy cycles were greater in the NC group compared with the PS group (9 [range, 4-30] vs 6 [range, 3-19];P< 0.01). The PS group was also more likely to undergo chemotherapy regimens involving platinum and taxane treatment compared with the NC group (79% vs 65%;P= 0.017). Total time undergoing primary chemotherapy from initial diagnosis was greater in the NC group compared with PS (223 vs 151 days;P< 0.01). No significant difference was observed in overall survival and progression-free survival in the 2 groups.Conclusions:In patients with advanced ovarian cancer, NC followed by abdominal hysterectomy is associated with improved perioperative outcomes including optimal cytoreduction, decreased blood loss, and decreased inpatient hospitalization. In this cohort, NC was also associated with prolonged chemotherapy treatment intervals and increased chemotherapy cycles without improvement in survival.

The Impact of Agent Orange Exposure On Presentation and Prognosis of Patients with Chronic Lymphocytic Leukemia (CLL): An Exploratory Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4575-4575
Author(s):  
Lisa M Baumann Kreuziger ◽  
Vicki A. Morrison
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Doubling Time ◽  
Hazard Ratio ◽  
Lymphocytic Leukemia ◽  
Agent Orange ◽  
Disease Stage ◽  
Younger Age ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4575 Background: From 1962–1971, 19 million gallons of Agent Orange (AO) and other herbicides were sprayed in South Vietnam and Cambodia to destroy dense jungle and crops used to conceal and feed enemy troops. In 2004, the Department of Veterans Affairs added chronic lymphocytic leukemia (CLL) to the list of Veterans Diseases Associated with Agent Orange, based upon data from agricultural exposure suggesting a causative association. In our retrospective cohort study, we evaluated if Agent Orange exposure was associated with an altered prognosis, time to treatment, or overall survival in veterans with newly diagnosed CLL. Methods: Clinical data was reviewed from 205 patients (pts) with CLL diagnosed from 2000–2010, identified through the Minneapolis MN VA Tumor Registry. Demographic information and laboratory parameters at diagnosis were collected, and Rai disease stage, marrow cytogenetics and lymphocyte doubling time were determined. Baseline labs, lymphocyte doubling time and time to initial CLL treatment were compared between exposed and unexposed pts using Student's t-test. Kaplan Meier analysis compared overall survival between Agent Orange-exposed and unexposed pts. Results: Of the 199 (97%) pts confirmed to have CLL, 33 pts (16.6%) had Agent Orange exposure. Median follow-up time was 40.7 months (0.1–123 months). Pts with Agent Orange exposure were younger at diagnosis (61 vs. 72 years, p=0.001). WBC, hemoglobin, platelet count, Rai stage, and LDH at diagnosis were similar between the groups. Mean lymphocyte doubling time was comparable in exposed and unexposed pts (27 vs. 23 months (mos), respectively p=0.6). Cytogenetic analysis was limited as 24% of pts underwent a bone marrow biopsy. Poor risk cytogenetics (17p-, 11q-) were found in 1 of 10 (10%) pts with Agent Orange exposure and 3 of 37 (8%) unexposed pts. Time to first CLL treatment was significantly shorter in pts with Agent Orange exposure [9.6 (range 0.1–23.7) vs. 30.2 mos (range 0.1–163.3), respectively; p=0.02]. No significant difference in reason for treatment initiation was found between the groups. First line fludarabine therapy was used more often in exposed than unexposed pts, which may have been due to their younger age at diagnosis (100% AO exposed vs 36% AO unexposed, Fisher's Exact p=0.01). No difference in overall survival was found between exposed and unexposed pts (Wilcoxon p=0.28). In a multivariable Cox regression model adjusted for age, Agent Orange exposure had a hazard ratio of death of 1.8 compared to non-exposure (95% CI: 0.7– 4.5, p = 0.24). Conclusions: CLL pts with Agent Orange exposure were diagnosed at a younger age and had a shorter time to first treatment, as compared to unexposed pts. Agent Orange exposure was not associated with a difference in prognosis in these patients. Although our hazard ratio result was not statistically significant, the high estimate of the mortality hazard combined with the relatively low numbers in the exposure group suggest that further examination of this issue in a larger patient population is warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Regulation of Interleukin-8 Expression in Human Endometrial Endothelial Cells: A Potential Mechanism for the Pathogenesis of Endometriosis

2005 ◽  
Vol 90 (3) ◽  
pp. 1805-1811 ◽  
Author(s):  
Janelle Luk ◽  
Yasemin Seval ◽  
Umit A. Kayisli ◽  
Murat Ulukus ◽  
Cagnur E. Ulukus ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sex Steroids ◽  
Cycle Phase ◽  
Eutopic Endometrium ◽  
Protein Levels ◽  
Cytokine Levels ◽  
Mrna And Protein Expression ◽  
The Relationship

The elevation of the proinflammatory chemoattractant cytokine levels in ectopic and eutopic endometrium of endometriosis implies an inflammatory basis for this disease. The relationship between endothelial cells and leukocytes is likely to be important in the regulation of inflammatory mediators of endometriosis. The aim of this study was to describe the temporal and spatial expression of IL-8 in human endometrial endothelial cells (HEEC) in vivo and to compare the in vitro regulation of IL-8 expression by sex steroids in HEEC from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to menstrual cycle phase and examined by immunohistochemistry for IL-8 expression. Endothelial cells of endometriotic implants expressed higher IL-8 immunoreactivity compared with endothelial cells of eutopic endometrium from women with or without endometriosis (P &lt; 0.02). For in vitro studies, HEEC were isolated from women with or without endometriosis and grown to preconfluence. The purity of cultured HEEC (90–95%) was confirmed by immunocytochemistry using endothelium-specific markers, CD31 and CD146. The effects of estradiol (5 × 10−8m), progesterone (10−7m), or both on IL-8 mRNA and protein levels were analyzed by RT-PCR and ELISA, respectively. Sex steroids reduced the expression of IL-8 mRNA and protein in HEEC from women without endometriosis. In contrast, both estradiol and progesterone stimulated IL-8 mRNA and protein expression in HEEC from women with endometriosis. We postulate that the stimulation of chemokine expression by sex steroids in HEEC of women with endometriosis may play a role in the inflammatory aspect of this disease.

scholarly journals Racial disparities in papillary thyroid microcarcinoma survival

2016 ◽  
Vol 131 (1) ◽  
pp. 83-87 ◽  
Author(s):  
U C Megwalu ◽  
A T Saini
Keyword(s):  
Overall Survival ◽  
Disease Stage ◽  
Papillary Thyroid Microcarcinoma ◽  
Study Cohort ◽  
Racial Groups ◽  
Papillary Thyroid ◽  
Thyroid Microcarcinoma ◽  
Black Patients ◽  
Significant Difference ◽  
The Impact

AbstractObjective:To evaluate the impact of race on survival in patients with papillary thyroid microcarcinoma.Methods:The study cohort included 17 668 patients diagnosed with papillary thyroid microcarcinoma between 1988 and 2009, identified in the Surveillance, Epidemiology, and End Results 18 database of the National Cancer Institute.Results:Black patients had lower overall survival than other racial groups (p < 0.001). Black patients had significantly worse overall survival (hazard ratio = 2.59) after adjusting for sex, marital status, age, year of diagnosis, multifocal disease and type of surgery. A subset analysis of Black patients revealed no significant difference in overall survival for total thyroidectomy versus lobectomy (p = 0.15).Conclusion:Black race is a negative prognostic factor in thyroid cancer, which cannot be explained by advanced disease stage. Further research on mechanisms by which race affects survival is needed to reveal areas of opportunity for interventions aimed at reducing health disparities in cancer care.

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