scholarly journals Characterization of guinea pig megakaryocyte subpopulations at different phases of maturation prepared with a Celsep separation system

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1801-1808 ◽  
Author(s):  
PK Schick ◽  
BP Schick ◽  
K Williams-Gartner
Keyword(s):  
Guinea Pig ◽  
Stage I ◽  
Stage Iii ◽  
Ploidy Class ◽  
Group 3 ◽  
Group 2 ◽  
Von Willebrand ◽  
Immature Cells ◽  
Willebrand Factor ◽  
Group 1

Abstract We introduce a new method for preparing subpopulations of guinea pig megakaryocytes (MK). MK, partially purified by a density gradient, were separated according to size by sedimentation, starting as a monolayer, in an albumin gradient at unit gravity. Twenty-two fractions were collected. Cells were cytocentrifuged, ploidy was assessed by microdensitometry, and small MK were identified with anti-von Willebrand factor (vWF) immunoglobulin. Immaturity was assessed by uptake of 3H thymidine and synthesis of proteoglycans from 35S sulfate. About 88% of cells in fractions 2 through 18 were MK, of which 90% were viable. Fractions containing the largest cells were composed of 98% stage III and IV MK; fractions with the smallest cells contained up to 80% stage I and II MK. Six MK classes were isolated: immature cells, both stage I and II cells, at either the 8N, 16N or 32N ploidy class; mature cells, both stage III and IV cells, at either the 8N, 16N or 32N ploidy class. The fractions were pooled into three groups: (a) 8% of MK in group 1, fractions 2 through 11, were immature, and group 1 was composed of 92% of 16N and 32N mature classes; (b) 29% of MK in group 2, fractions 12 through 15, were immature, and group 2 was composed of 52% 16N mature, 24% 16N immature, and 13% 8N mature classes; 67% of MK in group 3, fractions 16 through 18, were immature, and group 3 contained 51% 8N immature, 14% 16N immature, and 18% mature 16N classes. The mean protein content of the three groups was 1.251, 0.624, and 0.284 mg/10(6) MK, respectively. Nine percent of cells in group 3 but no cells in group 1 took up large amounts of 3H thymidine. The synthesis of high-molecular-weight (high-mol-wt) proteoglycans in group 3 and synthesis of lower mol wt proteoglycans in groups 1 and 2 provided further evidence for differences in MK maturity. Thus, the method can isolate MK subpopulations that are viable and can be used to investigate the biochemical characteristics of MK at different phases of maturation.

scholarly journals Characterization of guinea pig megakaryocyte subpopulations at different phases of maturation prepared with a Celsep separation system

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1801-1808
Author(s):  
PK Schick ◽  
BP Schick ◽  
K Williams-Gartner
Keyword(s):  
Guinea Pig ◽  
Stage I ◽  
Stage Iii ◽  
Ploidy Class ◽  
Group 3 ◽  
Group 2 ◽  
Von Willebrand ◽  
Immature Cells ◽  
Willebrand Factor ◽  
Group 1

We introduce a new method for preparing subpopulations of guinea pig megakaryocytes (MK). MK, partially purified by a density gradient, were separated according to size by sedimentation, starting as a monolayer, in an albumin gradient at unit gravity. Twenty-two fractions were collected. Cells were cytocentrifuged, ploidy was assessed by microdensitometry, and small MK were identified with anti-von Willebrand factor (vWF) immunoglobulin. Immaturity was assessed by uptake of 3H thymidine and synthesis of proteoglycans from 35S sulfate. About 88% of cells in fractions 2 through 18 were MK, of which 90% were viable. Fractions containing the largest cells were composed of 98% stage III and IV MK; fractions with the smallest cells contained up to 80% stage I and II MK. Six MK classes were isolated: immature cells, both stage I and II cells, at either the 8N, 16N or 32N ploidy class; mature cells, both stage III and IV cells, at either the 8N, 16N or 32N ploidy class. The fractions were pooled into three groups: (a) 8% of MK in group 1, fractions 2 through 11, were immature, and group 1 was composed of 92% of 16N and 32N mature classes; (b) 29% of MK in group 2, fractions 12 through 15, were immature, and group 2 was composed of 52% 16N mature, 24% 16N immature, and 13% 8N mature classes; 67% of MK in group 3, fractions 16 through 18, were immature, and group 3 contained 51% 8N immature, 14% 16N immature, and 18% mature 16N classes. The mean protein content of the three groups was 1.251, 0.624, and 0.284 mg/10(6) MK, respectively. Nine percent of cells in group 3 but no cells in group 1 took up large amounts of 3H thymidine. The synthesis of high-molecular-weight (high-mol-wt) proteoglycans in group 3 and synthesis of lower mol wt proteoglycans in groups 1 and 2 provided further evidence for differences in MK maturity. Thus, the method can isolate MK subpopulations that are viable and can be used to investigate the biochemical characteristics of MK at different phases of maturation.

scholarly journals Blood Plasma Serotonin and von Willebrand Factor as Biomarkers of Unstable Angina Progression Toward Myocardial Infarction

2021 ◽  
Vol 28 (1) ◽  
pp. E202112
Author(s):  
Yuliya Tyravska ◽  
Oleksandr Savchenko ◽  
Viktor Lizogub ◽  
Nataliia Raksha ◽  
Olexiy Savchuk
Keyword(s):  
Myocardial Infarction ◽  
Blood Plasma ◽  
Von Willebrand Factor ◽  
Serotonin Concentration ◽  
Group 3 ◽  
Group 2 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Plasma Serotonin ◽  
Group 1

Aim: To investigate the serotonin and von Willebrand factor (vWF) concentrations among unstable angina (UA) patients without and with progression toward myocardial infarction (outcome) and to assess the utility of both as prognostic markers of UA complications. Materials and methods: In observational cohort study, we recruited 103 patients with ischemic heart disease (the median age 65.0 (59.0-69.0) years, 45 females (43.7%)). After full set of investigations including high sensitive Troponin I test and 28-day follow-up period, we defined three groups: Group 1 - stable angina patients (n=22) as control, Group 2 - UA patients without outcome (n=71), Group 3 - UA patients with outcome (n=10). We analyzed the blood plasma serotonin content by the ion-exchange chromatography with measurement of serotonin on fluorescence spectrophotometer. VWF concentration was determined by ELISA. We compared the concentrations of observed parameters among the groups with the Kruskal-Wallis test (with post-hoc Mann-Whitney test with Bonferroni-Holm correction). We assessed binary logistic models, receiver operating characteristic curves, calculated sensitivity (Se), specificity (Sp), and positive likelihood ratio (LR+) for each indicator. Results: We registered elevation in serotonin concentration and decline in vWF concentration in Group 3 in comparison with Group 2 (22.670 (20.687-24.927) μg/ml vs 11.980 (8.120-15.000) μg/ml, p< 0.001, and 0.117 (0.109-0.120) rel.units/ml vs 0.134 (0.127-0.143) rel.units/ml, p < 0.001) and Group 1 (12.340 (10.052-13.619) μg/ml, p < 0.001, and 0.137 (0.127-0.156) rel.units/ml, p < 0.001), respectively. No significant differences in serotonin and vWF concentrations between Group 1 and Group 2 were detected (p=0.81 and p=0.36, respectively). The probability of outcome increased significantly (by 60.7% and 59.7%, LR+ 19.0 [6.0, 60.0] and 18.0 [3.9, 80.0]) if serotonin concentration was above 21.575 μg/ml (Se=80.0%, Sp=95.8%, AUC=0.975) and vWF concentration was below 0.114 rel.units/ml (Se=50.0%, Sp=97.2%, AUC=0.973), respectively. Conclusions: Serotonin and vWF as biomarkers are demonstrated promising results for rule-in the patients with risk of short-term UA progression toward myocardial infarction.

Hodgkin Lymphoma: 20 Years Experience From a Single Brazilian Institution

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3153-3153
Author(s):  
Camila C.G. Linardi ◽  
Luis Fernando Pracchia ◽  
Rodrigo Dolphini Velasques ◽  
Claudia Bitti Barroso ◽  
Valeria Buccheri
Keyword(s):  
Prognostic Factors ◽  
Hodgkin Lymphoma ◽  
Developed Countries ◽  
Stage I ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Free Survival ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Abstract 3153 Hodgkin Lymphoma (HL) is characterized by high cure rates. Approximately 90% early stage and 60–70% advanced stage patients have long term disease free survival. In Brazil it is observed that about 60% of patients present with advanced stage, while in developed countries about 40% belong to this group. The aim of this retrospective study was to analyze data of patients with HL from the Oncohematology Unit of University of São Paulo- Medical School and evaluate the event free survival (EFS) and the overall survival (OS) according to clinical stage. We included all consecutive patients diagnosed with HL between January 1991 and June 2010. The collection of data from medical records was done and the following variables at diagnosis were evaluated: age and sex, staging according to Cotswolds modified Ann-Arbor criteria (CS), histological subtype, presence of B symptoms and bulky disease, International Prognostic Index (IPI) according to International Prognostic Factors Project on Advanced Hodgkin's Disease, laboratorial data, and the protocol used in first line therapy. The complete remission (CR) rate, EFS and OS were analyzed in all patients. The survival analysis was estimated by the Kaplan-Meier method and the survival curves were compared by the log-rank test. Differences in CR rates among staging groups were compared using the chi squared test. Overall, 564 HL patients were identified; thirteen did not have adequate information about clinical staging and were excluded from the analysis. The median age, at diagnosis, of the remaining 551 patients was 28 (12–83) and 54.3% were male. Histological subtypes lymphocyte rich classical HL, nodular sclerosis, mixed cellularity and lymphocyte depletion were found in 3.6%, 51.4%, 24.2% and 5.6% cases, respectively, and 11.8% patients were diagnosed as HL classic not classifiable otherwise. Nodular lymphocyte predominance was observed in 3.3% cases. Stage I, II, III and IV were found in 42 (7.6%), 208 (37.7%), 145 (26.3%) e 156 (28.3%) patients, respectively. B symptoms and bulky disease were present in 65.5%and 58.8% patients, respectively. After staging the patients were divided in three groups: group 1 -CS I/II, without B symptoms nor bulky disease= 62 (11.25%) patients, group 2 -CS I/ II, with B symptoms and/or bulky disease=188 (34.12%) patients and group 3- CS III/ IV= 301 (54.62%) patients. IPI high risk score was recognized in 63.9% patients of group 3. Only 1.5% of patients were treated with exclusive radiotherapy. Of the patients that were treated with chemotherapy, 4.9% were treated with MOPP, 23.1% with MOPPABV, 70.5% with ABVD and 1.5% with other types of chemotherapy. The median follow-up of the entire cohort was 59.6 months (0–258.8 months) and 88.3% (CI 95%: 85.2%-91.1%) were in CR at the end of treatment (CS I: 100%, CS II: 90.6% CS III: 84.6% and CS IV: 85.3%; p=0.03) (group 1: 98.2%, group 2: 90.2% and group 3: 84.9%; p=0.012). The 5-year EFS rate was 69.2% (CS I: 84.8%; CS II: 77.8%; CS III: 64.5%, CS IV: 56%; p=0.0008) (group 1: 88%, group 2: 76% and group 3: 60.3%; p=0.0002) (Figures 1 and 2). The 5-year OS rate was 86.44% (CS I: 90.3%, CS II: 94.6%, CS III: 87.6%, CS IV: 71.4%; p<0.0001) (group 1: 98.3%, group 2: 92.6% and group 3: 79, 6%; p=0.0003).Figure 1Figure 1. Figure 2Figure 2. We found that there were more advanced stage patients (stage III/IV) in comparison to developed countries, however, patients classified as stage I/II without poor prognostic factors, like B symptoms and/or bulky disease, showed high rates of CR, EFS and OS. These data suggest that there is a need to enhance early diagnosis in Brazilian patients, in order to detect less advanced stage patients due to late diagnosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2013
Author(s):  
Wai-Shan Chung ◽  
Po-Hsien Le ◽  
Chiang-Jung Kuo ◽  
Tsung-Hsing Chen ◽  
Chang-Fu Kuo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gastric Cancer ◽  
Recurrence Risk ◽  
Tumour Recurrence ◽  
Stage I ◽  
Stage Iii ◽  
Metformin Group ◽  
Insignificant Difference ◽  
Group 2 ◽  
Group 1

Studies have shown the anticancer effects of metformin in vitro. However, whether metformin can prevent cancer recurrence or prolong survival in patients with gastric cancer (GC) and diabetes mellitus (DM) post-gastrectomy remains unknown. We evaluated the beneficial effects of metformin in patients with GC and DM post-gastrectomy. We recruited 2400 patients with GC (1749 without DM, 651 with DM) who underwent surgery between 1997 and 2010. Patients with DM were stratified into metformin (group 1) and non-metformin (group 2) users. Their clinicopathological data were recorded prospectively, and demographics, recurrence-free survival (RFS), and cancer-specific survival (CSS) were compared. Tumour recurrence risk and cause of death were analysed between groups 1 and 2 among patients with DM stratified by tumour stage. We also compared RFS and overall survival among patients with and without DM. Tumour recurrence occurred in 201 patients with GC: 57 (25%) in group 1 and 144 (37%) in group 2. After adjusting for confounders, metformin significantly prolonged CSS (hazard ratio (HR) = 0.54, 95% confidence interval (CI) = 0.38–0.77) in patients with stage I–III GC and DM. In subgroup analysis, metformin users with stage III GC and DM had significantly prolonged CSS compared to non-metformin users (HR = 0.45, 95% CI = 0.30–0.68), with an insignificant difference in patients with stage I–II GC. Adjusted HRs for RFS and CSS were significantly lower in patients with stage I–III GC and DM than those in patients without DM (0.67 (95% CI = 0.54–0.92) and 0.62 (95% CI = 0.50–0.77), respectively), with an insignificant difference in patients with stage I GC. Metformin significantly reduces tumour recurrence risk and improves CSS in patients with stage III GC and DM post-gastrectomy. Further prospective studies may confirm the efficacy of metformin as an adjunctive treatment for advanced GC postoperatively.

scholarly journals Krim Ekstrak Buah Merah (Pandanus conoideus ) 10% Sama Efektifnya dengan Krim Hidrokuinon 4% dalam Mencegah Peningkatan Jumlah Melanin Kulit Marmut (Cavia porcellus) yang Dipapar Sinar Ultraviolet B

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Corazon H. Dumaria ◽  
A AGP Wiraguna ◽  
Wimpie Pangkahila
Keyword(s):  
Guinea Pig ◽  
Ultraviolet B ◽  
Control Group ◽  
Control Group Design ◽  
Group Design ◽  
Significant Difference ◽  
Post Test ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract: This study was aimed to prove that administration of 10% redfruit extract cream could prevent the increase of skin melanin in guinea pig exposed to UVB and to compare this effect with 4% hydroquinone cream. This was a true experimental study using post test only control group design. Subjects were devided into three groups; each of 10 guinea pigs. Group 1, the control group, was exposed to UVB and applied with basic cream. Group 2 was exposed to UVB and applied with 4% hydroquinone cream. Group 3 was exposed to UVB and applied with 10% redfruit extract cream. The total dose of UVB was 390 mJ/cm2 given for 2 weeks. The amount of melanin was calculated using the percentage of the pixel area of melanin and was compared with the pixel areas of all epidermal tissues. The results showed that the highest percentage of melanin area was in group 1 (19.78%±3.79%). The percentage of melanin area in group 3 was 1.25%±0.76% meanwhile in group 2 was 0.85%±0.37%. There were signi-ficant differences in melanin percentage between the control group and group 2 as well as group 3 (P <0.05). There was no significant difference in melanin percentage between group 2 and group 3 (P >0.05). Conclusion: The 10% redfruit extract cream could prevent the increase of skin melanin in guinea pig exposed to UVB as effectively as the 4% hydroquinone cream.Keywords: redfruit extract cream, melanin, UVBAbstrak: Penelitian ini bertujuan untuk membuktikan efek pemberian krim ekstrak buah merah 10% dalam mencegah peningkatan jumlah melanin kulit marmut yang dipapar sinar UVB dan perbandingannya dengan krim hidrokuinon 4%. Jenis penelitian ialah eksperimental murni dengan post test only control group design. Sampel terdiri dari tiga kelompok dengan jumlah sampel 10 ekor marmut jantan tiap kelompok. Kelompok 1 yaitu kelompok kontrol, diberi paparan sinar UVB dan diolesi krim dasar. Kelompok 2 diberi paparan sinar UVB dan diolesi krim hidrokuinon 4%. Kelompok 3 diberi paparan sinar UVB dan diolesi krim ekstrak buah merah 10%. Dosis total UVB yaitu 390 mJ/cm2 diberikan selama 2 minggu. Jumlah melanin dihitung dengan persentase pixel luas area melanin dibandingkan dengan pixel seluruh jaringan epidermis. Hasil penelitian menunjukkan jumlah melanin tertinggi pada kelompok 1 (19,78± 3,79%) dan terendah pada kelompok 2 (0,85±0,37%), sedangkan jumlah melanin pada kelompok 3 di antara keduanya (1,25±0,76%). Terdapat perbedaan bermakna antara kelompok 1 dengan kelompok 2 dan 3 (P <0,05). Tidak terdapat perbedaan bermakna antara kelompok 2 dan 3 dalam mencegah peningkatan jumlah melanin (P >0,05 ). Simpulan: Krim ekstrak buah merah 10% dapat mencegah peningkatan jumlah melanin kulit marmut yang dipapar sinar UVB sama efektif dengan krim hidrokuinon 4%.Kata kunci: krim ekstrak buah merah, melanin, UVB

Intergroup Rhabdomyosarcoma Study-IV: Results for Patients With Nonmetastatic Disease

2001 ◽  
Vol 19 (12) ◽  
pp. 3091-3102 ◽  
Author(s):  
William M. Crist ◽  
James R. Anderson ◽  
Jane L. Meza ◽  
Christopher Fryer ◽  
R. Beverly Raney ◽  
...  
Keyword(s):  
Stage I ◽  
Embryonal Tumors ◽  
Primary Tumor Site ◽  
Free Survival ◽  
Eyelid Tumors ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
To Receive ◽  
Group 1

PURPOSE: The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy. PATIENTS AND METHODS: Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT). RESULTS: Overall 3-year FFS and survival were 77% and 86%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P = .42). No significant difference in outcome was noted with HF-RT versus C-RT (P = .85 and P = .90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%. CONCLUSION: VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.

Effect of introduction of paclitaxel on survival among women with stage III and IV ovarian cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5536-5536
Author(s):  
S. S. Dawood ◽  
C. Albaracin ◽  
A. Gonzalez-Angulo ◽  
M. Markman ◽  
B. Hennessy
Keyword(s):  
Ovarian Cancer ◽  
Stage Iv ◽  
Stage Iii ◽  
First Line ◽  
Fda Approval ◽  
Significant Difference ◽  
Stage Iv Disease ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

5536 Background: The objective of this study was to evaluate survival over time in relation to FDA approval of paclitaxel (P) for second- and first-line treatment in a population-based cohort of women with stage III and de novo stage IV ovarian cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) program was searched to identify 8,267 and 10,746 women with stage III and stage IV epithelial ovarian cancer diagnosed between 1988–2004. Women were divided according to their year of diagnosis and year of FDA approval of P for second- (1992) and first-line(1998) treatment of ovarian cancer: Group1 (1988–1991; before P approval); Group2 (1992–1997; P approved for second-line); Group3 (1998–2003; P approved for first-line). Overall (OS) and ovarian-cancer-specific survival (OCS) were estimated using Kaplan-Meier product method and compared across groups with log rank statistic. Cox-proportional hazards models were fitted to determine the association of group year of diagnosis and survival after adjusting for patient/tumor characteristics. Results: Median age was 66 years. Median OCS was 44 and 18 months among women with stages III and IV disease, respectively. With stage III disease, 2-year OCS was 64%, 68%, and 70% for groups 1, 2, and 3, respectively (p < 0.0001). With stage IV disease, 2-year OCS was 39%, 41%, and 42% for groups 1, 2, and 3, respectively (p = 0.19). In the multivariable model for stage III disease, women in group 1 (HR = 1.4, 95% CI 1.2–1.5, p < 0.0001) and group 2 (HR = 1.2, 95% CI 1.1–1.3, p = 0.0003) had an increased hazard of ovarian-cancer-specific death vs. group 3. For stage IV disease, women in group 1 (HR = 1.2, 95% CI 1.12–1.3, p < 0.0001) had a significantly increased hazard of ovarian cancer-specific death, but no significant difference in group 2 (HR = 1.0, 95% CI 0.9–1.1, p = 0.88) vs. group 3. Similar trends were observed for OS. Conclusions: The survival of women with stages III and IV ovarian cancer has significantly improved with the introduction of P over the last two decades. However, the incremental improvement in survival with stage IV disease is clinically minimal and indeed not significant in the univariable analysis in the SEER patient cohort analyzed, suggesting a desperate need for new and more active drugs in these patients. No significant financial relationships to disclose.

Retrospective analysis of the role of CA 15-3 as a biomarker for breast cancer relapse.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23051-e23051 ◽  
Author(s):  
Marwan Elahi Shaikh ◽  
Samantha Hall ◽  
Sijin Wen ◽  
Hui Liu ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Retrospective Analysis ◽  
Bone Pain ◽  
Stage I ◽  
Group 3 ◽  
Group 2 ◽  
Patient’S History ◽  
Relapse Group ◽  
Group 1

e23051 Background: The latest ASCO guidelines regarding tumor markers in breast cancer do not recommend routine monitoring of serum CA 15-3 (CA) levels alone as a marker for relapse. They do, however, acknowledge their use in conjunction with a patient’s history, physical exam, and diagnostic imaging. The study objective is to evaluate CA as a marker for relapse and determine its continued use in our patient population. Methods: We performed a retrospective analysis on female stage I-III breast cancer patients with an elevated CA marker treated in our cancer center between 2009-2014. Patients with metachronous or synchronous malignancies were excluded. Patients were categorized into three groups: Group 1 (elevated CA at relapse), Group 2 (normal CA at relapse, with elevation post-relapse), Group 3 (elevated CA without relapse). Categorical variables were collected to fulfill our objectives and the Fisher’s exact test was used to assess the correlation between them. The incidence rate and its 95% confidence interval were estimated based on the binomial distribution. Results: Out of 340 initially screened patients, 92 met our inclusion criteria: Group 1 (n = 25), Group 2 (n = 23), Group 3 (n = 44). The PPV for an elevated CA as a marker for relapse was 36% (95% CI: 26-48%). On routine surveillance, patients with elevated CA levels were more likely to have relapse if they presented with nausea (p = 0.02), myalgia (p = 0.003), or axial bone pain (p = 0.04). At relapse, an elevated CA was associated with fatigue (p = 0.02), myalgia (p = 0.01), liver metastases (p = 0.01), axial bone metastases (p = 0.005), and peripheral bone metastases (p = 0.0002). In patients with an elevated CA, a BMI < 25 had a higher incidence of relapse in comparison to those with a BMI ≥ 25 (p = 0.01). Conclusions: Our study suggests that a patient’s history, physical, and symptom-dictated imaging should be the main way to screen for relapse in stage I-III breast cancer. Based on the higher incidence of relapse in patients with both an elevated CA and symptoms of nausea, myalgia, or axial bone pain, we conclude that serum CA levels may be used as an adjunctive test in symptomatic patients. Our data also suggests that elevated CA levels may be less useful in detecting relapse in patients with BMI ≥ 25.

Association of HER2 alterations and ESR1 mutations in cell-free DNA (cfDNA) with circulating tumor cells (CTCs), multiple metastasis, and prognosis in stage III/IV breast cancer (BCa).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1036-1036
Author(s):  
Qiang Zhang ◽  
Lorenzo Gerratana ◽  
Ami N. Shah ◽  
Andrew A. Davis ◽  
Lisa E. Flaum ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Endocrine Resistance ◽  
Treatment Resistance ◽  
Stage Iii ◽  
Treatment Benefit ◽  
Group 4 ◽  
Group 3 ◽  
Esr1 Mutations ◽  
Group 2 ◽  
Group 1

1036 Background: The monitoring of CTCs and cfDNA in metastatic BCa showed ability to predict treatment resistance and survival. Here we report a highly significant correlation between HER2 alterations and ESR1 mutations of cfDNA with CTCs and prognosis of BCa, which may help to predict disease recurrence and treatment benefit. Methods: A total of 85 blood samples (7.5ml/each) were collected from 85 patients with stage III/IV BCa who received treatments at Northwestern RHLCCC. CTC enumeration was performed in FDA approved CELLTRACKS ANALYZERII System (Menarini). Plasma cfDNA was analyzed using Guardant360 NGS-based assay including a 73-gene panel for genomic alterations or mutations. We previously reported cut-off of 5.7% (2018 ASCO) was used to dichotomize the prognostic value of cfDNA percentage. Kruskal-Wallis test was used for statistics. Results: Of the 85 whole samples analyzed, there were 72 samples and 67 samples without ESR1 mutations (ESR1-) and HER2 alterations ( HER2-) respectively, and there are 13 samples and 18 samples that had ESR1 mutations ( ESR1+) and HER2 alterations ( HER2+, 10 amplified, 7 mutated, 1 for both) respectively. CTC positive (≥5) were detected in 13/57 ESR1-HER2- samples (Group 1) and 5/15 ESR1- HER2+ samples (Group 2), 7 /10 ESR1+ HER2- samples (Group 3), 3/3 ESR1+ HER2+ samples (Group 4). The median CTCs number/sample in Group 3 (15 CTCs) and Group 4 (12 CTCs) were significantly higher than Group 1 (0 CTC) and Group 2 (2 CTCs) (P = 0.0020). There were a significant higher average metastasis sites in Group 3 (3 sites) and Group 4 (3 sites) in compared to Group 1 (2 sites) and Group 2 (1 site) (P = 0.0035). Furthermore, patients in Group 4 ( ESR1+ HER2+) has the worst prognosis in compared to other groups (P = 0.0151) on overall survival. Conclusions: Both ESR1 mutations and HER2 alterations in cfDNA contribute to CTCs detection and disease metastasis sites independently, when ESR1 mutations plays a major role. The synergy of ESR1 mutation and HER2 alteration expands the predictive role of liquid biopsy tests monitoring the metastatic prognosis and endocrine resistance for clinical decision-making.

scholarly journals Effect of minimally invasive extracorporeal circulation on endothelial dysfunction in cardiac ­surgery patients

2020 ◽  
Vol 101 (2) ◽  
pp. 279-283
Author(s):  
V I Kornev ◽  
N M Kalinina ◽  
O N Startseva
Keyword(s):  
Cardiopulmonary Bypass ◽  
Endothelial Dysfunction ◽  
Minimally Invasive ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Activated Platelets ◽  
Group 2 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Group 1

Aim. To assess the changes in endothelial dysfunction in patients undergoing cardiac surgery with minimally invasive extracorporeal circulation (MiECC). Methods. The study included 50 patients who were undergoing coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB). The patients were divided assigned to either a minimally invasive cardiopulmonary bypass system (group 1, n=15) or standard extracorporeal circuit (group 2, n=35). Changes in the laboratory parameters were assessed 5 times: before the operation, 5 minutes after protamine sulfate administration, 12 hours after the operation, 7 days after the patient's discharged from the hospital and one month after the operation. The activity of von Willebrand factor, factor VIII, and the number of activated platelets were examined in all patients in venous blood. Results. After protamine sulfate administration, the activity of von Willebrand factor was increased to 164% in the group 1, and up to 193% in the group 2, with a tendency to increase the indicator after 12 hours. The peak of endothelial dysfunction, with the growth of von Willebrand factor and factor VIII, occurs on the 7th day after the operation. In patients of the group with MiECC, von Willebrand factor activity was decreased at the hospital discharge and returned to normal in 1 month. The number of activated platelets increases mainly in group 2 (6% versus 4% in group 1, p=0.29). The expression of P-selectin was significantly higher in group 2 at the hospital discharge (5.5% versus 3.1% in group 1, p 0.001), and in 1 month (4.5% versus 2.3% in group 1, p 0.001). Conclusion. In patients with minimally invasive cardiopulmonary bypass, platelet activation decreases, endothelial dysfunction, accompanied by an increase in the von Willebrand factor and factor VIII activity, is less pronounced; the seventh day after surgery is a period of the high risk of thrombogenic complications.

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