192 research outputs found
Multicenter fresh frozen tissue sampling in colorectal cancer: does the quality meet the standards for state of the art biomarker research?
The growing interest in the molecular subclassification of colorectal cancers is increasingly facilitated by large multicenter biobanking initiatives. The quality of tissue sampling is pivotal for successful translational research. This study shows the quality of fresh frozen tissue sampling within a multicenter cohort study for colorectal cancer (CRC) patients. Each of the seven participating hospitals randomly contributed ten tissue samples, which were collected following Standard Operating Procedures (SOP) using established techniques. To indicate if the amount of intact RNA is sufficient for molecular discovery research and prove SOP compliance, the RNA integrity number (RIN) was determined. Samples with a RIN < 6 were measured a second time and when consistently low a third time. The highest RIN was used for further analysis. 91% of the tissue samples had a RIN ā„ 6 (91%). The remaining six samples had a RIN between 5 and 6 (4.5%) or lower than 5 (4.5%). The median overall RIN was 7.3 (range 2.9ā9.0). The median RIN of samples in the university hospital homing the biobank was 7.7 and the median RIN for the teaching hospitals was 7.3, ranging from 6.5 to 7.8. No differences were found in the outcome of different hospitals (p = 0.39). This study shows that the collection of high quality fresh frozen samples of colorectal cancers is feasible in a multicenter design with complete SOP adherence. Thus, usin
Determination of Ki-67 defined growth fraction by monoclonal antibody MIB- I in formalin-fixed, paraffin-embedded prostatic cancer tissues
The applicability of MIBā1, a monoclonal antibody directed against the Kiā67 antigen, was studied in the PCā82 and LNCaP prostatic tumor models at various levels of proliferative activity. Statistically significant correlations were found in LNCaP cultures between Kiā67 and MIBā1 scores (r = 0.84, P < 0.001), and in PCā82 tumors between MIBā1 scores and paraffin tissue Kiā67 (pKiā67) (r = 0.90, P < 0.001), frozen tissue Kiā67 (fKiā67) (r = 0.86, P < 0.001), and BrdU uptake (r = 0.70, P < 0.001), respectively. pKiā67 scores were double the fKiā67 scores, which may be due to methodological differences. MIBā1 scores exceeded both the fKiā67 and pKiā67 scores. The affinity of MIBā1 for the antigen is much higher than the affinity of Kiā67, which may explain the differences. MIBā1 is a promising means of evaluating the presence of only minute amounts of the Kiā67 antigen in paraffināembedded human tumor material, especially in relatively slowly growing tumors
Expression and prognostic value of Wilms' tumor 1 and early growth response 1 proteins in nephroblastoma
Expression and prognostic value of Wilms' tumor 1 and early growth response 1 proteins in nephroblastoma
Wilms' tumor is one of the most common solid tumors of children. The
protein product of the tumor-suppressor gene, Wilms' tumor 1 (WT-1), binds
to the same DNA sequences as the protein product of the early growth
response 1 (EGR-1) gene. There is experimental evidence that EGR-1 is
involved in controlling cell growth. The expression of both genes in
Wilms' tumor was studied by others, mainly at the mRNA level. The present
study evaluates the prognostic value of WT-1 and EGR-1 in 61 Wilms' tumors
of chemotherapeutically treated patients at the protein level, using an
immunohistochemical approach. WT-1 was expressed in normal kidney tissues
and in the blastemal and epithelial component of Wilms' tumor, whereas
stromal tissue was negative. EGR-1 was expressed in normal kidney tissues
and in the three main cell types of Wilms' tumor. In 59 and 56% of Wilms'
tumor, the blastemal cells stained for WT-1 and EGR-1, respectively. The
blastemal expression of WT-1 and EGR-1 and the epithelial expression of
WT-1 were statistically significantly correlated with clinical stage. WT-1
immunoreactivity correlated with EGR-1 expression. Univariate analysis
showe
Kinetics of neuroendocrine differentiation in an androgen-dependent human prostate xenograft model
It was previously shown in the PC-295 xenograft that the number of
chromogranin A (CgA)-positive neuroendocrine (NE) cells increased after
androgen withdrawal. NE cells did not proliferate and differentiated from
G0-phase-arrested cells. Here we further characterized NE differentiation,
androgen receptor status, and apoptosis-associated Bcl-2 expression in the
PC-295 model after androgen withdrawal to assess the origin of NE cells.
PC-295 tumor volumes decreased by 50% in 4 days. Intraperitoneal
bromodeoxyuridine (BrdU) incorporation and MIB-1 labeling decreased to 0%,
and the apoptosis was maximal at day 4. Androgen receptor expression and
prostate-specific antigen (PSA) serum levels decreased rapidly within 2
days. The number of NE cells increased 6-fold at day 4 and 30-fold at day
7. Five and ten percent of the CgA-positive cells were BrdU positive after
continuous BrdU labeling for 2 and 4 days, respectively. However, no MIB-1
expression was observed in CgA-positive cells. NE cells expressed the
regulated secretory pathway marker secretogranin III but were negative for
androgen receptor and Bcl-2. Bcl-2 expression did increase in the non-NE
tumor cells. In conclusion, androgen withdrawal leads to a rapid PC-295
tumor regression and a proliferation-independent induction of NE
differentiation. The strictly androgen-independent NE cells that were
still present after 21 days differentiated mainly from G0-phase-arrested
cells
The SAFE-trial:Safe surgery for glioblastoma multiforme: Awake craniotomy versus surgery under general anesthesia. Study. protocol for a multicenter prospective randomized controlled trial
Background: Surgery of GBM nowadays is usually performed under general anesthesia (GA) and resections are often not as aggressive as possible, due to the chance of seriously damaging the patient with a rather low life expectancy. A surgical technique optimizing resection of the tumor in eloquent areas but preventing neurological deficits is necessary to improve survival and quality of life in these patients. Awake craniotomy (AC) with the use of cortical and subcortical stimulation has been widely implemented for low-grade glioma resections (LGG), but not yet for GBM. AC has shown to increase resection percentage and preserve quality of life in LGG and could thus be of important value in GBM surgery. Methods/design: This study is a prospective, multicenter, randomized controlled trial (RCT). Consecutive patients with a glioblastoma in or near eloquent areas (Sawaya grading II/III) will be 1:1 randomized to awake craniotomy or craniotomy under general anesthesia. 246 patients will be included in neurosurgical centers in the Netherlands and Belgium. Primary end-points are: 1) Postoperative neurological morbidity and 2) Proportion of patients with gross-total resections. Secondary end-points are: 1) Health-related quality of life; 2) Progression-free survival (PFS); 3) Overall survival (OS) and 4) Frequency and severity of Serious Adverse Effects in each group. Also, a cost-benefit analysis will be performed. All patients will receive standard adjuvant treatment with concomitant chemoradiotherapy. Discussion: This RCT should demonstrate whether AC is superior to craniotomy under GA on neurological morbidity, extent of resection and survival for glioblastoma resections in or near eloquent areas. Trial registration: Clinicaltrials.gov: NCT03861299 Netherlands Trial Register (NTR): NL758
Composition of Human Thrombus Assessed by Quantitative Colorimetric Angioscopic Analysis.
Background Angioscopy surpasses other diagnostic tools, such as angiography and intravascular ultrasound, in detecting arterial thrombus. This capability arises in part from the unique ability of angioscopy to assess true color during imaging. In practice, hardware-induced chromatic distortions and the subjectivity of human color perception subs
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