scholarly journals Impact of Blood Vessel Quantity and Vascular Expression of CD133 and ICAM-1 on Survival of Glioblastoma Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ave Minajeva ◽  
Marju Kase ◽  
Mikk Saretok ◽  
Aidi Adamson-Raieste ◽  
Sandra Kase ◽  
...  
Keyword(s):  
Overall Survival ◽  
Blood Vessel ◽  
Blood Vessels ◽  
Median Survival ◽  
Antiangiogenic Therapy ◽  
Staining Intensity ◽  
Survival Times ◽  
Microvascular Proliferation ◽  
High Median ◽  
Vascular Expression

Glioblastoma (GB) is the most angiogenic tumor. Nevertheless, antiangiogenic therapy has not shown significant clinical efficacy. The aim of this study was to assess blood vessel characteristics on survival of GB patients. Surgically excised GB tissues were histologically examined for overall proportion of glomeruloid microvascular proliferation (MP) and the total number of blood vessels. Also, immunohistochemical vascular staining intensities of CD133 and ICAM-1 were determined. Vessel parameters were correlated with patients’ overall survival. The survival time depended on the number of blood vessels (p=0.03) but not on the proportion of MP. Median survival times for patients with low (<median) and high (≥median) number of blood vessels were 9.0 months (95% CI: 7.5–10.5) and 12.0 months (95% CI: 9.3–14.7). Also, median survival times for patients with low (<median) and high (≥median) vascular expression level of CD133 were 9.0 months (95% CI: 8.0–10.1) and 12.0 months (95% CI: 10.3–13.7). In contrast, the staining intensity of vascular ICAM-1 did not affect survival. In multivariate analysis, the number of blood vessels emerged as an independent predictor for longer overall survival (HR: 2.4, 95% CI: 1.2–5.0, p=0.02). For success in antiangiogenic therapy, better understanding about tumor vasculature biology is needed.

A novel intermediate endpoint for predicting overall survival in men with metastatic castration-recurrent prostate cancer (CRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5113-5113 ◽  
Author(s):  
S. Halabi ◽  
S. Ou ◽  
N. J. Vogelzang ◽  
H. Scher ◽  
E. J. Small
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Clinical Benefit ◽  
Opioid Analgesic ◽  
Performance Status ◽  
Phase Iii ◽  
Training Dataset ◽  
Survival Times ◽  
Androgen Ablation ◽  
Three Components

5113 Background: In this proposed study, we developed and validated a novel composite clinical benefit endpoint constructed from symptoms that have intrinsic clinical importance in 800 men with CRPC who were treated with front-line chemotherapy. Methods: Data from nine multimember trials (five phase II and four randomized phase III studies) conducted by the Cancer and Leukemia Group B (CALGB) from 1992–2004 were combined. Eligible patients had progressive adenocarcinoma of the prostate during androgen ablation (despite castrate testosterone levels), an ECOG performance status of 0–2, adequate hematologic, renal and hepatic functions. The tripartite composite clinical benefit endpoint (TCCBE) had three components: one based on disease progression (whether it be PSA, bone, or soft tissue progression), and the second based on weight loss (defined as at least 10% decline from baseline) or on performance status (PS) decline (by at least one level) to capture clinical deterioration. The third component was based on pain control and opioid analgesic use (no or yes). For a person to fall in the TCCBE “yes” category, at least two of the three components had to be recorded as no. For instance, if a patient at 3 months had no progression, no change in weight and did not use opioid analgesic, then he will be classified in the “yes” group and for the purpose of this analysis was considered as someone who achieved “clinical benefit”. The sample was randomly split into 526 (67%) and 274 (33%) men in the training and testing datasets, respectively. Results: From the training dataset, the median survival times in men who had and did not have clinical benefit were 20.9 months (95% confidence interval (CI) = 18.5–22.8) and 11.1 months (95% = 8.79–12.6, p- value<0.001). In the testing dataset, the median survival times in men with and without clinical benefit were 21.7 months (95% CI= 19.1–26.1) and 8.8 months (95% CI= 7.8–11.6) and in men. The hazard ratio (HR) for men with a clinical benefit compared to men without was 0.52 (95% CI= 0.43–0.62, P<0.001). Conclusions: The TCCBE is a statistically significant intermediate endpoint for predicting overall survival. Prospective validation of this endpoint is needed. No significant financial relationships to disclose.

High- versus low-dose leucovorin in the modified FOLFOX6 regimen for first-line treatment of metastatic colorectal cancer

2016 ◽  
Vol 23 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Jana Reynolds ◽  
April Chamberland-Tremblay ◽  
Jon D Herrington ◽  
Yolanda Munoz Maldonado ◽  
Lucas Wong
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Retrospective Study ◽  
Metastatic Colorectal Cancer ◽  
Median Survival ◽  
High Dose ◽  
Survival Times ◽  
First Line ◽  
Metastatic Site ◽  
Modified Folfox6

Background In response to the national leucovorin shortage in 2008, our institution adjusted the modified FOLFOX6 (leucovorin, fluorouracil, and oxaliplatin) protocol to utilize a lower dose of leucovorin (20 mg/m2). This adjustment was based on prospective studies suggesting that lower doses of leucovorin may be equally effective in other fluorouracil containing regimens. This retrospective study evaluates outcomes in metastatic colorectal cancer (mCRC) patients treated with low- (20 mg/m2) vs. high-dose (400 mg/m2) leucovorin in the FOLFOX6 regimen for mCRC. Methods This retrospective analysis included consecutive mCRC patients from 2004 to 2011 if they received at least one cycle of modified FOLFOX6 as first line therapy. Patients who received an initial leucovorin dose other than 20 mg/m2 or 400 mg/m2 on their first cycle were excluded. Patient characteristics included demographics, metastatic site at initial diagnosis, and treatment history including chemotherapy and surgery. Primary outcome was date of death or last contact. Cox proportional hazards regression analysis and Kaplan–Meier survival curves were utilized to evaluate the effect of leucovorin dose on overall survival. Log-rank tests were used to compare median survival times by dose group. Results Of the 93 mCRC patients who received first line modified FOLFOX6, leucovorin 400 mg/m2 was administered to 47 (51%) patients and 20 mg/m2 to 46 (49%) patients. There were no differences of baseline characteristics between the groups with exception of primary site of cancer ( p = 0.038). The overall survival time was 22.5 months (95% CI 16.6–29.6). The median survival time in the leucovorin 400 mg/m2 group was 23.1 months (95% CI 16.2–35.7) compared to leucovorin 20 mg/m2 which was 20.5 months (95% CI 14.2–34.2); p = 0.573. The median survival times in patients with one versus two or more sites with metastasis were statistically different (26.9 vs. 16.2 months, p = 0.009). Metastatic site removal or ablation showed differences in the median survival, 34.2 months (95% CI 20.8–50.9) vs. 16.6 months (95% CI 14.1–23.6) without metastatic disease removal ( p = 0.004). The odds of dying for patients with two metastatic sites was higher compared with the odds of those patients with one site, HR 1.8 (95% CI 1.08–3.0). Patients without metastatic site removal or ablation had higher odds of dying compared to those patients without this procedure, HR 0.47 (95% CI 0.27–0.81). Conclusion In this single center retrospective study, there was no difference in overall survival for mCRC patients treated with first line FOLFOX6 with low- vs. high-dose leucovorin.

scholarly journals VEGFR-2 Expression in Glioblastoma Multiforme Depends on Inflammatory Tumor Microenvironment

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jana Jaal ◽  
Marju Kase ◽  
Ave Minajeva ◽  
Mikk Saretok ◽  
Aidi Adamson ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Microenvironment ◽  
Blood Vessels ◽  
Optical Density ◽  
Antiangiogenic Therapy ◽  
Growth Factor Receptor ◽  
Positive Association ◽  
Staining Intensity ◽  
Tissue Expression ◽  
The Impact

Glioblastoma multiforme (GBM) is one of the most angiogenic tumors. However, antiangiogenic therapy has not shown significant clinical efficacy. The aim of our study was to evaluate the impact of inflammatory tumor microenvironment on the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). Surgically excised primary GBM tissues were histologically examined for overall extent of inflammation (score 1–3). After immunohistochemistry, the tissue expression of ICAM-1 (optical density), the number of VEGFR-2 positive (VEGFR-2+) blood vessels (per microscopic field), and the endothelial staining intensity of VEGFR-2 (score 0–3) were determined. In GBM, the extent of inflammation was 1.9 ± 0.7 (group mean ± SD). Mean optical density of inflammatory mediator ICAM-1 was 57.0 ± 27.1 (pixel values). The number of VEGFR-2+ blood vessels and endothelial VEGFR-2 staining intensity were 6.2 ± 2.4 and 1.2 ± 0.8, respectively. A positive association was found between endothelial VEGFR-2 staining intensity and the extent of inflammation (p=0.005). Moreover, VEGFR-2 staining intensity correlated with the expression level of ICAM-1 (p=0.026). The expression of VEGFR-2, one of the main targets of antiangiogenic therapy, depends on GBM microenvironment. Higher endothelial VEGFR-2 levels were seen in the presence of more pronounced inflammation. Target dependence on inflammatory tumor microenvironment has to be taken into consideration when treatment approaches that block VEGFR-2 signaling are designed.

Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma: Recursive Partitioning Analysis of the EORTC 26981/22981-NCIC CE3 Phase III Randomized Trial

2006 ◽  
Vol 24 (16) ◽  
pp. 2563-2569 ◽  
Author(s):  
René-Olivier Mirimanoff ◽  
Thierry Gorlia ◽  
Warren Mason ◽  
Martin J. Van den Bent ◽  
Rolf-Dieter Kortmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Recursive Partitioning ◽  
Survival Rates ◽  
Recursive Partitioning Analysis ◽  
Survival Advantage ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Survival Times ◽  
European Organisation

Purpose The European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada trial on temozolomide (TMZ) and radiotherapy (RT) in glioblastoma (GBM) has demonstrated that the combination of TMZ and RT conferred a significant and meaningful survival advantage compared with RT alone. We evaluated in this trial whether the recursive partitioning analysis (RPA) retains its overall prognostic value and what the benefit of the combined modality is in each RPA class. Patients and Methods Five hundred seventy-three patients with newly diagnosed GBM were randomly assigned to standard postoperative RT or to the same RT with concomitant TMZ followed by adjuvant TMZ. The primary end point was overall survival. The European Organisation for Research and Treatment of Cancer RPA used accounts for age, WHO performance status, extent of surgery, and the Mini-Mental Status Examination. Results Overall survival was statistically different among RPA classes III, IV, and V, with median survival times of 17, 15, and 10 months, respectively, and 2-year survival rates of 32%, 19%, and 11%, respectively (P < .0001). Survival with combined TMZ/RT was higher in RPA class III, with 21 months median survival time and a 43% 2-year survival rate, versus 15 months and 20% for RT alone (P = .006). In RPA class IV, the survival advantage remained significant, with median survival times of 16 v 13 months, respectively, and 2-year survival rates of 28% v 11%, respectively (P = .0001). In RPA class V, however, the survival advantage of RT/TMZ was of borderline significance (P = .054). Conclusion RPA retains its prognostic significance overall as well as in patients receiving RT with or without TMZ for newly diagnosed GBM, particularly in classes III and IV.

Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10581-10581
Author(s):  
Sherif S. Morgan ◽  
Raymond B. Nagle ◽  
Lee D. Cranmer
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Median Survival ◽  
Prognostic Significance ◽  
Significant Proportion ◽  
Soft Tissue Sarcomas ◽  
Staining Intensity ◽  
Cellular Adhesion ◽  
Elevated Expression ◽  
Sparc Expression

10581 Background: SPARC is a matricellular secreted glycoprotein that performs several functions, including modulating cellular adhesion and proliferation. It has been implicated in tumorigenesis and identified as an adverse prognostic factor in a number of cancers. The specific mechanisms involved have yet to be identified. Agents targeting SPARC-expressing tumors, such as nanoparticle albumin-bound-paclitaxel (NAB-P), have been developed. Soft tissue sarcomas (STS) represent a heterogeneous group of tumors with inadequate systemic therapies. Our objective was to explore the pattern of SPARC expression and its prognostic significance in STS. Methods: Formalin-fixed paraffin-embedded tissue sections were stained by immunohistochemistry using a mouse monoclonal antibody for SPARC (Abnova). Staining intensity was scored blindly. Patient survival was determined from patients’ medical records. Kaplan-Meier and log-rank analyses were used to compare survival by SPARC expression level. Results: 27 tissue specimens of various STS subtypes were investigated (Table). Elevated SPARC expression was observed in 56% of specimens, but did not correlate with underlying histology. Overall survival segregated into 2 groups based on SPARC levels. Patients who expressed low-to-moderate levels of SPARC exhibited median survival of 22.1 months, while the median survival of patients with moderate-to-high expression levels was 4.4 months (log rank; p=0.0016). Conclusions: A significant proportion of STS specimens exhibit elevated SPARC expression. Elevated SPARC does not correlate with underlying histology, although analysis of a greater number of specimens might reveal subtypes with more frequently elevated expression. Overall survival segregates strongly by degree of SPARC expression, with elevated expression being adverse. Our results suggest that analysis in STS of agents targeting SPARC, such as NAB-P, should be stratified by extent of SPARC expression. [Table: see text]

scholarly journals Model for End-Stage Liver Disease and Sodium Velocity Predicts Overall Survival in Nonmetastatic Hepatocellular Carcinoma Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Justin Y. Tang ◽  
Nitin Ohri ◽  
Rafi Kabarriti ◽  
Santiago Aparo ◽  
Jennifer Chuy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Disease ◽  
Median Survival ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Survival Times ◽  
Short Term ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims. The significance of short-term changes in model for end-stage liver disease and Sodium (MELD-Na) following hepatocellular carcinoma (HCC) diagnosis is unknown. In this report, we explore the value of the rate of short-term changes in MELD-Na as an independent predictor of mortality in patients with nonmetastatic HCC. Methods. We reviewed a cohort of patients diagnosed with nonmetastatic HCC at our institution between 2001 and 2011. We evaluated potential predictors of overall survival, including baseline MELD-Na and the change in MELD-Na over 90 days. We explored survival times of cohorts grouped by baseline MELD-Na and the change in MELD-Na. Results. 182 patients met eligibility criteria. With a median follow-up of 21 months for surviving patients, 110 deaths were observed (60%). Median MELD-Na at the time of diagnosis was 9.7 (IQR 7.5 to 13.9). The median changes in percentage of MELD-Na over 90 days were an increase of 9% (IQR -4% to 55%). Multivariable Cox proportional hazards modeling demonstrated that both baseline MELD-Na (HR=1.07 per unit increase, 95% CI 1.03 to 1.11, p<0.001) and changes in MELD-Na exceeding 40% (HR=3.69, 95% CI 2.39 to 5.69, p<0.001) were independently associated with increased mortality risk. Median survival among patients whose changes in MELD-Na were greater than 40% was 4.5 months, and median survival among the 131 other patients was 25.8 months (p<0.001). Conclusions. We identified a subset of HCC patients who have extremely poor prognosis by incorporating the rate of short-term change in MELD-Na to baseline MELD-Na score.

scholarly journals Impact of CD133 positive stem cell proportion on survival in patients with glioblastoma multiforme

2013 ◽  
Vol 47 (4) ◽  
pp. 405-410 ◽  
Author(s):  
Marju Kase ◽  
Ave Minajeva ◽  
Kristi Niinepuu ◽  
Sandra Kase ◽  
Markus Vardja ◽  
...  
Keyword(s):  
Stem Cells ◽  
Overall Survival ◽  
Stem Cell ◽  
Glioblastoma Multiforme ◽  
Survival Time ◽  
Median Survival ◽  
Postoperative Radiotherapy ◽  
Study Group ◽  
Survival Times ◽  
Cell Proportion

Abstract Background. The aim of the study was to assess the impact of CD133-positive (CD133+) cancer stem cell proportions on treatment results of glioblastoma multiforme (GBM) patients. Patients and methods. Patients with GBM (n = 42) received postoperative radiotherapy (± chemotherapy). Surgically excised GBM tissue sections were immunohistochemically examined for CD133 expression. The proportions of CD133+ GBM cells were determined (%). The proportion of CD133+ GBM stem cells was established by 2 independent researchers whose results were in good accordance (R = 0.8, p < 0.01). Additionally, CD133 expression levels were correlated with patients overall survival. Results. The proportion of CD133+ cells varied between patients, being from 0.5% to 82%. Mean and median proportions of CD133+ cells of the entire study group were 33% ± 24% (mean ± SD) and 28%, respectively. Clinical data do not support the association between higher proportion of stem cells and the aggressiveness of GBM. Median survival time of the study group was 10.0 months (95% CI 9.0-11.0). The survival time clearly depended on the proportion of CD133+ cells (log rank test, p = 0.02). Median survival times for patients with low (< median) and high (≥ median) proportion of CD133+ cells were 9.0 months (95% CI 7.6-10.5) and 12.0 months (95% CI 9.3-14.7), respectively. In multivariate analysis, the proportion of CD133+ cells emerged as a significant independent predictor for longer overall survival (HR 2.0, 95% CI 1.0-3.8, p = 0.04). Conclusions. In patients with higher stem cell proportion, significantly longer survival times after postoperative radiotherapy were achieved. Underlying reasons and possible higher sensitivity of GBM stem cells to fractionated radiotherapy should be clarified in further studies.

Mixed photon and neutron radiotherapy given concurrently with chemotherapy in unresectable pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 328-328
Author(s):  
M. E. Christensen ◽  
P. Paximadis ◽  
A. F. Shields ◽  
P. A. Philip ◽  
D. W. Weaver ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Survival ◽  
Local Control ◽  
Neutron Radiation ◽  
Pancreatic Tumors ◽  
Tumor Control ◽  
Unresectable Pancreatic Cancer ◽  
Survival Times ◽  
Histologic Diagnosis

328 Background: Unresectable tumors of the pancreas remain difficult to treat despite the advent of targeted radiotherapy and modern chemotherapy. Randomized trials exploring the efficacy of chemotherapy and radiation have demonstrated median survival of 9 to 11 months. These survival times have not improved appreciably in the modern era. The purpose of this study was to retrospectively review our institutional experience with unresectable pancreatic cancer treated with mixed photon-neutron radiotherapy given concurrently with chemotherapy. Methods: Thirteen patients with unresectable tumors of the pancreas were treated between 1993 and 2001. All patients were treated with mixed photon-neutron radiotherapy given concurrently with chemotherapy. Median photon dose was 39.6 Gy (30.6-45Gy) and median neutron dose was 8 nGy (7-9 nGy). 12 of 13 patients were treated with neoadjuvant chemotherapy, followed by 5-FU given concurrently with radiotherapy. Median survival, overall survival, and local control were calculated for all patients. Results: The median age of all patients was 65 years (46-75 years). Twelve patients had histologic diagnosis of adenocarcinoma, with the other having an islet cell carcinoma. All patients are now deceased. Median survival for all patients was 11.5 months (3.0-25.6 months). The 1 and 2- year overall survival was 46.2% and 7.7%, respectively. Local control of the primary tumor was excellent at 92.3%. The rate of distant metastasis was 76.9%. One patient experienced decline without documented recurrence. No grade ≥3 acute toxicities were reported. However, there were 2 grade 5 late toxicities, both caused by gastrointestinal bleeding. Conclusions: Our experience demonstrates that treatment of unresectable pancreatic tumors with mixed photon-neutron radiotherapy given concurrently with chemotherapy results in excellent local control, with survival time equivalent to or exceeding that demonstrated in previous series. With the added capability of intensity modulated neutron radiation therapy (IMNRT), the incidence of treatment-related morbidity may be improved while taking advantage of the superior tumor control that high-LET radiation may impart. No significant financial relationships to disclose.

COMPARISON OF ANTIHYPERTENSIVE EFFECT OF MOXONIDINE VERSUS CLONIDINE IN RENAL FAILURE PATIENTS.

2018 ◽  
Vol 6 (9) ◽  
Author(s):  
DR.MATHEW GEORGE ◽  
DR.LINCY JOSEPH ◽  
MRS.DEEPTHI MATHEW ◽  
ALISHA MARIA SHAJI ◽  
BIJI JOSEPH ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Failure ◽  
Blood Flow ◽  
Blood Vessel ◽  
Blood Vessels ◽  
High Blood Pressure ◽  
Antihypertensive Effect ◽  
The Body ◽  
Ability To Work ◽  
Blood Flows

Blood pressure is the force of blood pushing against blood vessel walls as the heart pumps out blood, and high blood pressure, also called hypertension, is an increase in the amount of force that blood places on blood vessels as it moves through the body. Factors that can increase this force include higher blood volume due to extra fluid in the blood and blood vessels that are narrow, stiff, or clogged(1). High blood pressure can damage blood vessels in the kidneys, reducing their ability to work properly. When the force of blood flow is high, blood vessels stretch so blood flows more easily. Eventually, this stretching scars and weakens blood vessels throughout the body, including those in the kidneys.

scholarly journals Retinal Vessel Segmentation by Deep Residual Learning with Wide Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yuliang Ma ◽  
Xue Li ◽  
Xiaopeng Duan ◽  
Yun Peng ◽  
Yingchun Zhang
Keyword(s):  
Blood Vessel ◽  
Blood Vessels ◽  
Area Under The Curve ◽  
Retinal Vessel ◽  
Vessel Segmentation ◽  
Superior Performance ◽  
Retinal Blood Vessel ◽  
Low Contrast ◽  
Blood Vessel Segmentation ◽  
Small Vessels

Purpose. Retinal blood vessel image segmentation is an important step in ophthalmological analysis. However, it is difficult to segment small vessels accurately because of low contrast and complex feature information of blood vessels. The objective of this study is to develop an improved retinal blood vessel segmentation structure (WA-Net) to overcome these challenges. Methods. This paper mainly focuses on the width of deep learning. The channels of the ResNet block were broadened to propagate more low-level features, and the identity mapping pathway was slimmed to maintain parameter complexity. A residual atrous spatial pyramid module was used to capture the retinal vessels at various scales. We applied weight normalization to eliminate the impacts of the mini-batch and improve segmentation accuracy. The experiments were performed on the DRIVE and STARE datasets. To show the generalizability of WA-Net, we performed cross-training between datasets. Results. The global accuracy and specificity within datasets were 95.66% and 96.45% and 98.13% and 98.71%, respectively. The accuracy and area under the curve of the interdataset diverged only by 1%∼2% compared with the performance of the corresponding intradataset. Conclusion. All the results show that WA-Net extracts more detailed blood vessels and shows superior performance on retinal blood vessel segmentation tasks.

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