15 research outputs found
Proatherogenic sialidases and desialylated lipoproteins: 35 years of research and current state from bench to bedside
This review summarizes the main achievements in basic and clinical research of atheroscle-rosis. Focusing on desialylation as the first and the most important reaction of proatherogenic pathological cascade, we speak of how desialylation increases the atherogenic properties of low density lipoproteins and decreases the anti-atherogenic properties of high density lipoproteins. The separate sections of this paper are devoted to immunogenicity of lipoproteins, the enzymes contribut-ing to their desialylation and animal models of atherosclerosis. In addition, we evaluate the available experimental and diagnostic protocols that can be used to develop new therapeutic approaches for atherosclerosis.This research was funded by the Russian Science Foundation, grant number 18-15-00254
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A phase II study of neoadjuvant and adjuvant chemotherapy with 5-fluorodeoxyuridine, leucovorin, oxaliplatin and docetaxel in the treatment of previously untreated advanced esophageal adenocarcinoma
A complete pathologic response to neoadjuvant chemotherapy, without the use of radiation, has infrequently been reported in operable chemo-naïve stage III esophageal adenocarcinoma patients.
Twenty-nine eligible patients were enrolled in the study. Neoadjuvant therapy consisted of 5-fluorodeoxyuridine, leucovorin, oxaliplatin and docetaxel and was administered in two 4-week cycles. Following therapy, patients underwent surgical resection. Those patients having residual disease were offered adjuvant chemotherapy. Patients having a complete pathologic response were not offered any further chemotherapy.
Twenty-four out of 29 patients finished neoadjuvant therapy and underwent curative esophagectomy. Two patients were declared inoperable after treatment, and three patients died prior to surgery. The median follow-up on all patients was 20.2 months. Median progression-free survival and median overall survival were 13.6 and 21.4 months, respectively. Clinical response to neoadjuvant chemotherapy was seen in 21 out of 29 patients (72.4%). Complete pathologic response with neoadjuvant chemotherapy was seen in 4 out of 24 patients (16.7%). Those four patients have been alive and progression-free for 20-37 months. Grade 3-4 toxicities occurred in 16 of the 29 patients during neoadjuvant therapy. Grade 3-4 toxicities were seen in 6 out of 14 patients during adjuvant therapy. (18)F-fluorodeoxyglucose-positron emission tomography standardized uptake values of ≥8 correlated with better progression-free survival.
5-Fluorodeoxyuridine, leucovorin, oxaliplatin and docetaxel regimen is active in patients with esophageal adenocarcinoma. Toxicity profiles are manageable. Neoadjuvant chemotherapy allowed achievement of complete pathologic response without radiation. (18)F-fluorodeoxyglucose-positron emission tomography standardized uptake values might be prognostic
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A Phase I Study of 5-Fluorouracil/Leucovorin and Arsenic Trioxide for Patients with Refractory/Relapsed Colorectal Carcinoma
Neoadjuvant, Surgery and Adjuvant Chemotherapy without Radiation for Esophageal Cancer
Background
A phase II trial to evaluate neoadjuvant (NAD), surgery and adjuvant (AD) combination chemotherapy without radiation therapy (RT) for patients with esophageal adenocarcinoma staged with endoscopic ultrasound and CT as T3N1 was carried out.
Methods
Thirty-three eligible patients were enrolled. NAD therapy was administered in two 49-day cycles and included cisplatin, floxuridine, paclitaxel and leucovorin. Esophageal resection was performed followed by AD therapy.
Results
Thirty-three patients initiated NAD therapy; 10 experienced grade 3 and 4 toxicities, which included leucopenia, fatigue, nausea, diarrhea and stomatitis. Additionally, 16 patients experienced grade 1 and 2 hematologic and non-hematologic toxicities. Fifteen patients were down-staged, of whom five were T2, seven were T1, and three had nodal disease with no evidence of residual cancer in the esophageal bed. Fifteen patients remained T3, and two showed progressive disease. Thirty-two patients proceeded to surgery and 30 were resected. Although all resected patients were eligible for AD therapy, 15 did not receive it either because of patient refusal or surgeon recommendation. Fifteen patients received AD therapy: nine who had remained T3 and six who had down-staged. Three patients experienced grade 3 and 4 toxicities similar to those in NAD therapy. Six patients had grade 1 and 2 toxicities. Kaplan-Meier estimates of overall survival at 1, 3 and 5 years were 73% (95% CI: 58-88%), 52% (95% CI: 34-69%) and 29% (95% CI: 13-45%), respectively. Median survival was 42 months.
Conclusion
Deletion of RT may safely allow for more aggressive chemotherapy and increase chances of survival. The results need to be confirmed in a randomized phase II or larger phase III trial
Chromosome 18 Transcriptome Profiling and Targeted Proteome Mapping in Depleted Plasma, Liver Tissue and HepG2 Cells
The final goal of the Russian part of the Chromosome-centric
Human
Proteome Project (C-HPP) was established as the analysis of the chromosome
18 (Chr 18) protein complement in plasma, liver tissue and HepG2 cells
with the sensitivity of 10<sup>–18</sup> M. Using SRM, we have
recently targeted 277 Chr 18 proteins in plasma, liver, and HepG2
cells. On the basis of the results of the survey, the SRM assays were
drafted for 250 proteins: 41 proteins were found only in the liver
tissue, 82 proteins were specifically detected in depleted plasma,
and 127 proteins were mapped in both samples. The targeted analysis
of HepG2 cells was carried out for 49 proteins; 41 of them were successfully
registered using ordinary SRM and 5 additional proteins were registered
using a combination of irreversible binding of proteins on CN-Br Sepharose
4B with SRM. Transcriptome profiling of HepG2 cells performed by RNAseq
and RT-PCR has shown a significant correlation (<i>r</i> = 0.78) for 42 gene transcripts. A pilot affinity-based interactome
analysis was performed for cytochrome b5 using analytical and preparative
optical biosensor fishing followed by MS analysis of the fished proteins.
All of the data on the proteome complement of the Chr 18 have been
integrated into our gene-centric knowledgebase (www.kb18.ru)
Chromosome 18 Transcriptome Profiling and Targeted Proteome Mapping in Depleted Plasma, Liver Tissue and HepG2 Cells
The final goal of the Russian part of the Chromosome-centric
Human
Proteome Project (C-HPP) was established as the analysis of the chromosome
18 (Chr 18) protein complement in plasma, liver tissue and HepG2 cells
with the sensitivity of 10<sup>–18</sup> M. Using SRM, we have
recently targeted 277 Chr 18 proteins in plasma, liver, and HepG2
cells. On the basis of the results of the survey, the SRM assays were
drafted for 250 proteins: 41 proteins were found only in the liver
tissue, 82 proteins were specifically detected in depleted plasma,
and 127 proteins were mapped in both samples. The targeted analysis
of HepG2 cells was carried out for 49 proteins; 41 of them were successfully
registered using ordinary SRM and 5 additional proteins were registered
using a combination of irreversible binding of proteins on CN-Br Sepharose
4B with SRM. Transcriptome profiling of HepG2 cells performed by RNAseq
and RT-PCR has shown a significant correlation (<i>r</i> = 0.78) for 42 gene transcripts. A pilot affinity-based interactome
analysis was performed for cytochrome b5 using analytical and preparative
optical biosensor fishing followed by MS analysis of the fished proteins.
All of the data on the proteome complement of the Chr 18 have been
integrated into our gene-centric knowledgebase (www.kb18.ru)
Chromosome 18 Transcriptome Profiling and Targeted Proteome Mapping in Depleted Plasma, Liver Tissue and HepG2 Cells
The final goal of the Russian part of the Chromosome-centric
Human
Proteome Project (C-HPP) was established as the analysis of the chromosome
18 (Chr 18) protein complement in plasma, liver tissue and HepG2 cells
with the sensitivity of 10<sup>–18</sup> M. Using SRM, we have
recently targeted 277 Chr 18 proteins in plasma, liver, and HepG2
cells. On the basis of the results of the survey, the SRM assays were
drafted for 250 proteins: 41 proteins were found only in the liver
tissue, 82 proteins were specifically detected in depleted plasma,
and 127 proteins were mapped in both samples. The targeted analysis
of HepG2 cells was carried out for 49 proteins; 41 of them were successfully
registered using ordinary SRM and 5 additional proteins were registered
using a combination of irreversible binding of proteins on CN-Br Sepharose
4B with SRM. Transcriptome profiling of HepG2 cells performed by RNAseq
and RT-PCR has shown a significant correlation (<i>r</i> = 0.78) for 42 gene transcripts. A pilot affinity-based interactome
analysis was performed for cytochrome b5 using analytical and preparative
optical biosensor fishing followed by MS analysis of the fished proteins.
All of the data on the proteome complement of the Chr 18 have been
integrated into our gene-centric knowledgebase (www.kb18.ru)
Chromosome 18 Transcriptome Profiling and Targeted Proteome Mapping in Depleted Plasma, Liver Tissue and HepG2 Cells
The final goal of the Russian part of the Chromosome-centric
Human
Proteome Project (C-HPP) was established as the analysis of the chromosome
18 (Chr 18) protein complement in plasma, liver tissue and HepG2 cells
with the sensitivity of 10<sup>–18</sup> M. Using SRM, we have
recently targeted 277 Chr 18 proteins in plasma, liver, and HepG2
cells. On the basis of the results of the survey, the SRM assays were
drafted for 250 proteins: 41 proteins were found only in the liver
tissue, 82 proteins were specifically detected in depleted plasma,
and 127 proteins were mapped in both samples. The targeted analysis
of HepG2 cells was carried out for 49 proteins; 41 of them were successfully
registered using ordinary SRM and 5 additional proteins were registered
using a combination of irreversible binding of proteins on CN-Br Sepharose
4B with SRM. Transcriptome profiling of HepG2 cells performed by RNAseq
and RT-PCR has shown a significant correlation (<i>r</i> = 0.78) for 42 gene transcripts. A pilot affinity-based interactome
analysis was performed for cytochrome b5 using analytical and preparative
optical biosensor fishing followed by MS analysis of the fished proteins.
All of the data on the proteome complement of the Chr 18 have been
integrated into our gene-centric knowledgebase (www.kb18.ru)