115 research outputs found
Особенности и эффективность проведения геолого-технических мероприятий на Шингинском нефтяном месторождении (Томская область)
Целью данной работы является анализ эффективности проведенных геолого-технических мероприятий на Шингинском нефтяном месторождении. В процессе работы были выявлены наиболее эффективные, и наиболее часто проводимые ГТМ, а также рассчитана экономическая эффективность от проведения гидроразрыва пласта.The purpose of this work is to analyze the effectiveness of geological and technical measures carried out at the Shinginskoye field. In the course of the work, the most effective and most frequently performed geological and technical measures were determined and the economic efficiency of the hydraulic fracture was calculated
Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection
Simple Summary: Hepatocellular carcinoma remains a leading cause of cancer-related death and the most common primary hepatic malignancy in the Western hemisphere. Previous research found that angiogenesis-related cytokines and elevated levels of interleukin 8 and vascular endothelial growth factor (VEGF) shorten the expected time of survival. Moreover, factors of tumor angiogenesis- and hypoxia-driven signaling pathways are already associated with worse outcome in disease-free survival in several tumor entities. Our study investigates the prognosis of hepatocellular carcinoma patients based on a selection of ten different single-nucleotide polymorphisms from angiogenesis, carcinogenesis, and hypoxia pathways. Our study with 127 patients found supporting evidence that polymorphisms in angiogenesis-associated pathways corelate with disease-free survival and clinical outcome in patients with hepatocellular carcinoma.
Abstract: Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)-restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of "high-expression" variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients' individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery
Diagnostic and Prognostic Implications of FGFR3(high)/Ki67(high) Papillary Bladder Cancers
Prognostic/therapeutic stratification of papillary urothelial cancers is solely based upon histology, despite activated FGFR3-signaling was found to be associated with low grade tumors and favorable outcome. However, there are FGFR3-overexpressing tumors showing high proliferation-a paradox of coexisting favorable and adverse features. Therefore, our study aimed to decipher the relevance of FGFR3-overexpression/proliferation for histopathological grading and risk stratification. N = 142 (n = 82 pTa, n = 42 pT1, n = 18 pT2-4) morphologically G1-G3 tumors were analyzed for immunohistochemical expression of FGFR3 and Ki67. Mutation analysis of FGFR3 and TP53 and FISH for FGFR3 amplification and rearrangement was performed. SPSS 23.0 was used for statistical analysis. Overall FGFR3(high)/Ki67(high) status (n = 58) resulted in a reduced Delta mean progression-free survival (PFS) (p < 0.01) of 63.92 months, and shorter progression-free survival (p < 0.01;mean PFS: 55.89 months) in pTa tumors (n = 50). FGFR3(mut)/TP53(mut) double mutations led to a reduced Delta mean PFS (p < 0.01) of 80.30 months in all tumors, and FGFR3(mut)/TP53(mut) pTa tumors presented a dramatically reduced PFS (p < 0.001;mean PFS: 5.00 months). Our results identified FGFR3(high)/Ki67(high) papillary pTa tumors as a subgroup with poor prognosis and encourage histological grading as high grade tumors. Tumor grading should possibly be augmented by immunohistochemical stainings and suitable clinical surveillance by endoscopy should be performed
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Identification and validation of potential new biomarkers for prostate cancer diagnosis and prognosis using 2D-DIGE and MS
This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 (P < 0.044) in prostate cancer, while vinculin showed significant upregulation (P < 0.001). Secernin-1 overexpression in prostate tissue was validated using Western blot and immunohistochemistry while vinculin expression was validated using immunohistochemistry. These findings indicate that secernin-1 and vinculin are potential new tissue biomarkers for prostate cancer diagnosis and prognosis, respectively. For validation, protein levels in urine were also examined by Western blot analysis. Urinary vinculin levels in prostate cancer patients were significantly higher than in urine from nontumor patients (P = 0.006). Using multiple reaction monitoring-MS (MRM-MS) analysis, prostatic acid phosphatase (PAP) showed significant higher levels in the urine of prostate cancer patients compared to controls (P = 0.012), while galectin-3 showed significant lower levels in the urine of prostate cancer patients with biochemical relapse, compared to those without relapse (P = 0.017). Three proteins were successfully differentiated between patients with and without prostate cancer and patients with and without relapse by using MRM. Thus, this technique shows promise for implementation as a noninvasive clinical diagnostic technique
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Brief inhalation of nitric oxide increases resuscitation success and improves 7-day-survival after cardiac arrest in rats: a randomized controlled animal study
Introduction: Inhaled nitric oxide (iNO) improves outcomes when given post systemic ischemia/reperfusion injury. iNO given during cardiopulmonary resuscitation (CPR) may therefore improve return of spontaneous circulation (ROSC) rates and functional outcome after cardiac arrest (CA). Methods: Thirty male Sprague-Dawley rats were subjected to 10 minutes of CA and at least 3 minutes of CPR. Animals were randomized to receive either 0 (n = 10, Control), 20 (n = 10, 20 ppm), or 40 (n = 10, 40 ppm) ppm iNO during CPR until 30 minutes after ROSC. A neurological deficit score was assessed daily for seven days following the experiment. On day 7, brains, hearts, and blood were sampled for histological and biochemical evaluation. Results: During CPR, 20 ppm iNO significantly increased diastolic arterial pressure (Control: 57 ± 5.04 mmHg; 20 ppm: 71.57 ± 57.3 mmHg, p < 0.046) and decreased time to ROSC (Control: 842 ± 21 s; 20 ppm: 792 ± 5 s, (p = 0.02)). Thirty minutes following ROSC, 20 ppm iNO resulted in an increase in mean arterial pressure (Control: 83 ± 4 mmHg; 20 ppm: 98 ± 4 mmHg, p = 0.035), a less pronounced rise in lactate and inflammatory cytokine levels, and attenuated cardiac damage. Inhalation of NO at 20 ppm improved neurological outcomes in rats 2 to 7 days after CA and CPR. This translated into increases in 7 day survival (Control: 4; 20 ppm: 10; 40 ppm 6, (p ≤ 0.05 20 ppm vs Control and 40 ppm). Conclusions: Our study revealed that breathing NO during CPR markedly improved resuscitation success, 7-day neurological outcomes and survival in a rat model of VF-induced cardiac arrest and CPR. These results support the beneficial effects of NO inhalation after cardiac arrest and CPR
Clinical sequencing identifies potential actionable alterations in a high rate of urachal and primary bladder adenocarcinomas.
OBJECTIVE
Administration of targeted therapies provides a promising treatment strategy for urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC); however, the selection of appropriate drugs remains difficult. Here, we aimed to establish a routine compatible methodological pipeline for the identification of the most important therapeutic targets and potentially effective drugs for UrC and PBAC.
METHODS
Next-generation sequencing, using a 161 cancer driver gene panel, was performed on 41 UrC and 13 PBAC samples. Clinically relevant alterations were filtered, and therapeutic interpretation was performed by in silico evaluation of drug-gene interactions.
RESULTS
After data processing, 45/54 samples passed the quality control. Sequencing analysis revealed 191 pathogenic mutations in 68 genes. The most frequent gain-of-function mutations in UrC were found in KRAS (33%), and MYC (15%), while in PBAC KRAS (25%), MYC (25%), FLT3 (17%) and TERT (17%) were recurrently affected. The most frequently affected pathways were the cell cycle regulation, and the DNA damage control pathway. Actionable mutations with at least one available approved drug were identified in 31/33 (94%) UrC and 8/12 (67%) PBAC patients.
CONCLUSIONS
In this study, we developed a data-processing pipeline for the detection and therapeutic interpretation of genetic alterations in two rare cancers. Our analyses revealed actionable mutations in a high rate of cases, suggesting that this approach is a potentially feasible strategy for both UrC and PBAC treatments
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