Pseudomonas mandelii SW-3, isolated from the Napahai plateau wetland, can survive in cold environments. The mechanisms underlying the survival of bacteria in low temperatures and high altitudes are not yet fully understood. In this study, the whole genome of SW-3 was sequenced to identify the genomic features that may contribute to survival in cold environments. The results showed that the genome size of strain SW-3 was 6,538,059 bp with a GC content of 59%. A total of 67 tRNAs, a 34,110 bp prophage sequence, and a large number of metabolic genes were found. Based on 16S rRNA gene phylogeny and average nucleotide identity analysis among P. mandelii, SW-3 was identified as a strain belonging to P. mandelii. In addition, we clarified the mechanisms by which SW-3 survived in a cold environment, providing a basis for further investigation of host-phage interaction. P. mandelii SW-3 showed stress resistance mechanisms, including glycogen and trehalose metabolic pathways, and antisense transcriptional silencing. Furthermore, cold shock proteins and glucose 6-phosphate dehydrogenase may play pivotal roles in facilitating adaptation to cold environmental conditions. The genome-wide analysis provided us with a deeper understanding of the cold-adapted bacterium.
- MeSH
- DNA bakterií genetika MeSH
- fylogeneze * MeSH
- fyziologická adaptace * genetika MeSH
- genom bakteriální * MeSH
- nízká teplota * MeSH
- profágy genetika MeSH
- Pseudomonas * genetika klasifikace MeSH
- RNA ribozomální 16S * genetika MeSH
- sekvenování celého genomu MeSH
- zastoupení bazí MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Predictive markers can help tailor treatment to the individual in metastatic renal cell carcinoma (mRCC). De Ritis ratio (DRR) is associated with oncologic outcomes in various solid tumors. OBJECTIVE: To assess the value of DRR in prognosticating survival in mRCC patients treated with tyrosine-kinase inhibitors (TKI). METHODS: Overall, 220 mRCC patients treated with TKI first-line therapy were analyzed. An optimal cut-off point for DRR was determined with Youden's J. We used multiple strata for DRR, performed descriptive, Kaplan-Meier and multivariable Cox-regression analyses to assess associations of DRR with progression-free (PFS) and overall survival (OS). RESULTS: Patients above the optimal cut-off point for DRR of ≥ 1.58 had fewer liver metastases (p = 0.01). There was no difference in PFS (p > 0.05) between DRR groups. DRR above the median of 1.08 (HR 1.42; p = 0.03), DRR ≥ 1.1(HR 1.44; p = 0.02), ≥ 1.8 (HR 1.56; p = 0.03), ≥ 1.9 (HR 1.59; p = 0.02) and ≥ 2.0 (HR 1.63; p = 0.047) were associated with worse OS. These associations did not remain after multivariable adjustment. In the intermediate MSKCC group, DRR was associated with inferior OS at cut-offs ≥ 1.0 (HR 1.78; p = 0.02), ≥ 1.1 (HR 1.81; p = 0.01) and above median (HR 1.88; p = 0.007) in multivariable analyses. In patients with clear-cell histology, DRR above median (HR 1.54; p = 0.029) and DRR ≥ 1.1 (HR 1.53; p = 0.029) were associated with OS in multivariable analyses. CONCLUSION: There was no independent association between DRR and survival of mRCC patients treated with TKI in the entire cohort. However, OS of patients with intermediate risk and clear-cell histology were affected by DRR. DRR could be used for tailored decision-making in these subgroups.
- MeSH
- alanintransaminasa analýza krev MeSH
- analýza přežití MeSH
- aspartátaminotransferasy analýza krev MeSH
- cytoredukční chirurgie metody MeSH
- indazoly * aplikace a dávkování škodlivé účinky MeSH
- inhibitory proteinkinas aplikace a dávkování škodlivé účinky MeSH
- karcinom z renálních buněk * krev farmakoterapie patologie chirurgie MeSH
- Karnofského skóre MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ledvin * krev farmakoterapie patologie chirurgie MeSH
- nefrektomie metody MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- pyrimidiny * aplikace a dávkování škodlivé účinky MeSH
- sorafenib aplikace a dávkování škodlivé účinky MeSH
- staging nádorů MeSH
- stupeň nádoru MeSH
- sulfonamidy * aplikace a dávkování škodlivé účinky MeSH
- sunitinib * aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Urothelial cancer of the bladder (UCB) is usually a disease of the elderly. The influence of age on oncological outcomes remains controversial. This study aims to investigate the impact of age on UCB outcomes in Europe focusing particularly on young and very young patients. We collected data of 669 UCB patients treated with RC at our tertiary care center. We used various categorical stratifications as well as continuous age to investigate the association of age and tumor biology as well as endpoints with descriptive statistics and Cox regression. The median age was 67 years and the mean follow-up was 52 months. Eight patients (1.2%) were ≤40 years old and 39 patients (5.8%) were aged 41-50 years, respectively. In multivariable analysis, higher continuous age and age above the median were independent predictors for disease recurrence, and cancer-specific and overall mortality (all p-values ≤ 0.018). In addition, patients with age in the oldest tertile group had inferior cancer-specific and overall survival rates compared to their younger counterparts. Young (40-50 years) and very young (≤40 years) patients had reduced hazards for all endpoints, which, however, were not statistically significant. Age remains an independent determinant for survival after RC. Young adults did, however, not have superior outcomes in our analyses. Quality of life and complications are endpoints that need further evaluation in patients undergoing RC.
- Publikační typ
- časopisecké články MeSH