Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early ...diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation.
Proteomic analysis revealed 119 and 166 proteins for patients in stages I-II and III-IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (
< 0.01) for distinguishing stages I-II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression.
The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.
PURPOSE OF REVIEWConventional transurethral resection of bladder tumor (cTURBT) is the standard approach to the diagnosis and treatment of nonmuscle invasive bladder cancer. However, it suffers from ...inherent limitations such as insufficient assessment of resection depth and the need for intravesical tumor fragmentation that hampers histopathological evaluation. We summarize recent clinical data on en bloc resection of bladder tumor (ERBT), a method that promises to overcome these limitations.
RECENT FINDINGSThe PubMed/Medline databases were searched for reports on ERBT focusing on trends in the last 2 years. ERBT provides greater resection quality, making up to 95% of detrusor muscle available for pathological evaluation. ERBT also allows detection of the muscularis mucosae thus facilitating T1 substaging. Available data demonstrate no significant difference in perioperative morbidity. No conclusions can be drawn on the impact of either modality on tumor recurrence and progression, as the available data is too underpowered.
SUMMARYERBT is gaining acceptances as there is increasing evidence that it improves the quality of resected specimens. There seems to be no difference in perioperative morbidity between ERBT and cTURBT. The impact of ERBT on important endpoints such as recurrence and progression remains to be fully elucidated in further studies.
We sought to assess the prognostic value of variant histology in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.
We searched PubMed®, Web of Science™, Cochrane ...Library and Scopus® databases in May 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with upper tract urothelial carcinoma with or without variant histology. Formal meta-analyses were performed for these outcomes.
We identified 32 studies with 16,052 patients, including 26 studies with 12,865 patients that were eligible for the meta-analysis. Variant histology was associated with poor outcomes in terms of cancer specific (pooled HR 2.00, 95% CI 1.57 to 2.56), overall (pooled HR 1.76, 95% CI 1.51 to 2.04) and recurrence-free survival (pooled HR 1.64, 95% CI 1.42 to 1.89). Subgroup analyses revealed that micropapillary (pooled HR 3.02, 95% CI 1.71 to 5.34), and squamous and/or glandular variant histologies (pooled HR 1.48, 95% CI 1.14 to 1.92) were also associated with poor cancer specific survival.
Variant histology in patients with upper tract urothelial carcinoma is associated with an increased risk of cancer specific and overall mortality and disease recurrence. Furthermore, variant histology was independently associated with cancer specific survival in the micropapillary, and squamous and/or glandular variant histology subgroups. It may be useful to incorporate variant histology into prognostic tools that help guide patients and physicians in selecting appropriate treatment strategies for upper tract urothelial carcinoma.
Purpose
A superpulse (500 W peak power) thulium fiber laser operating at a 1940 nm wavelength, suitable for lithotripsy, has recently been developed. The goal of this study was to compare stone ...fragmentation and dusting performance of the prototype superpulse thulium fiber laser with leading commercially available, high-power holmium:YAG lithotripters (wavelength 2100 nm) in a controlled in vitro environment.
Methods
Two experimental setups were designed for investigating stone ablation rates and retropulsion effects, respectively. In addition, the ablation setup enabled water temperature measurements during stone fragmentation in the laser–stone interaction zone. Human uric acid (UA) and calcium oxalate monohydrate (COM) stones were used for ablation experiments, whereas standard BegoStone phantoms were utilized in retropulsion experiments. The laser settings were matched in terms of pulse energy, pulse repetition rate, and average power.
Results
At equivalent settings, thulium fiber laser ablation rates were higher than those for holmium:YAG laser in both dusting mode (threefold for COM stones and 2.5-fold for UA stones) and fragmentation mode (twofold for UA stones). For single-pulse retropulsion experiments, the threshold for onset of stone retropulsion was two to four times higher for thulium fiber laser. The holmium:YAG laser generated significantly stronger retropulsion effects at equal pulse energies. The water temperature elevation near the laser-illuminated volume did not differ between the two lasers.
Conclusions
Distinctive features of the thulium fiber laser (optimal wavelength and long pulse duration) resulted in faster stone ablation and lower retropulsion in comparison to the holmium:YAG laser.
A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The developed method was successfully ...applied to pharmacokinetic studies. The sample preparation process included solid-phase extraction (SPE). Effective chromatographic separation of the analytes and internal standard (dalargin) was achieved with a C18 column, using a gradient elution with two mobile phases: 0.1%
/
formic acid (aqueous solution) and 0.1%
/
formic acid (acetonitrile solution). The linearity of the method was demonstrated within a concentration range of 0.5-20 ng/mL, with correlation coefficients between 0.998-0.999 for goserelin, buserelin, triptorelin, and octreotide, respectively. The relative standard deviation (RSD, %) values for method accuracy and precision did not exceed 20% at the lower level of quantitation (LLOQ) or 15% at other concentration levels.
Purpose
To evaluate the efficacy and safety of thulium-fiber laser (TFL) in laser lithotripsy during percutaneous nephrolithotomy (PCNL).
Methods
Patients with stones < 30 mm were prospectively ...recruited to undergo PCNL using TFL “FiberLase” (NTO IRE-Polus, Russia). Stone size, stone density, operative time, and “laser on” time (LOT) were recorded. Study included only cases managed with fragmentation. Stone-free rate and residual fragments were determined on postoperative computer tomography. Complications were classified using the Clavien–Dindo grade. Stone retropulsion and endoscopic visibility were assessed based on surgeons’ feedback using a questionnaire.
Results
A total of 120 patients were included in the study with a mean age of 52 (± 1.8) years; of these 77 (56%) were males. Mean stone size was 12.5 (± 8.8) mm with a mean density of 1019 (± 375) HU. Mean operative time was 23.4 (± 17.9) min and mean LOT was 5.0 (± 5.7) min. Most used settings were of 0.8 J/25–30 W/31–38 Hz (fragmentation). The mean total energy for stone ablation was 3.6 (± 4.3) kJ. Overall stone-free rate was 85%. The overall complication rate was 17%. Surgeons reported stone retropulsion that interfered with surgery in 2 (1.7%) cases insignificant retropulsion was noted in 16 (10.8%) cases. Poor visualization was reported in three (2.5%) cases and minor difficulties with visibility in four (3.3%) cases.
Conclusions
TFL is a safe and effective modality for lithotripsy during PCNL and results in minimal retropulsion.
Post-translational processing leads to conformational changes in protein structure that modulate molecular functions and change the signature of metabolic transformations and immune responses. Some ...post-translational modifications (PTMs), such as phosphorylation and acetylation, are strongly related to oncogenic processes and malignancy. This study investigated a PTM pattern in patients with gender-specific ovarian or breast cancer. Proteomic profiling and analysis of cancer-specific PTM patterns were performed using high-resolution UPLC-MS/MS. Structural analysis, topology, and stability of PTMs associated with sex-specific cancers were analyzed using molecular dynamics modeling. We identified highly specific PTMs, of which 12 modified peptides from eight distinct proteins derived from patients with ovarian cancer and 6 peptides of three proteins favored patients from the group with breast cancer. We found that all defined PTMs were localized in the compact and stable structural motifs exposed outside the solvent environment. PTMs increase the solvent-accessible surface area of the modified moiety and its active environment. The observed conformational fluctuations are still inadequate to activate the structural degradation and enhance protein elimination/clearance; however, it is sufficient for the significant modulation of protein activity.
We assessed the prognostic value of sex differences in upper tract urothelial carcinoma and urothelial carcinoma of the bladder treated with radical surgery.
The PubMed®, Web of Science®, Cochrane ...Library and Scopus® databases were searched in July 2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies were deemed eligible if they compared overall, cancer specific, and recurrence-free survival in patients with upper tract urothelial carcinoma and urothelial carcinoma of the bladder. Formal meta-analyses were performed for these outcomes according to sex differences.
Overall 66 studies with 100,389 patients with urothelial carcinoma of the bladder and 40 studies with 39,759 patients with upper tract urothelial carcinoma were eligible for review and meta-analysis. Female patients with urothelial carcinoma of the bladder were associated with worse cancer specific survival (pooled HR 1.20, 95% CI 1.10-1.31), overall survival (pooled HR 1.03, 95% CI 1.01-1.05) and recurrence-free survival (pooled HR 1.13, 95% CI 1.02-1.25). In contrast, those with upper tract urothelial carcinoma were not associated with cancer specific survival (pooled HR 0.94, 95% CI 0.89-1.00), overall survival (pooled HR 0.98, 95% CI 0.95-1.01) and recurrence-free survival (pooled HR 0.90, 95% CI 0.78-1.03).
Sex is associated with cancer specific mortality, overall mortality and disease recurrence in urothelial carcinoma of the bladder but not in upper tract urothelial carcinoma. Given the genetic and social differences between the sexes, sex differences may represent a key factor in the clinical decision making process.
Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified ...an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies.
We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I
statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months).
A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months).
Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.
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