Search results for "kr"
showing 10 items of 7011 documents
Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non–Small Cell Lung Cancer
2013
Abstract Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non–small cell lung cance…
Liver Transplantation for Unresectable Intrahepatic Cholangiocarcinoma: The Role of Sequencing Genetic Profiling
2021
Simple Summary Intrahepatic cholangiocarcinoma is a rare disease with increasing incidence and mortality still characterized by an insufficient clinical outcome. Growing attention has recently surrounded this disease, and liver transplantation has emerged as a novel curative treatment for cholangiocarcinoma, along with a better understanding of genetic alterations potentially capable of driving tumorigenesis. The aim of this paper is to present a clinical description of our case series of patients affected by intrahepatic cholangiocarcinoma and by mixed forms of hepatocellular and cholangiocellular carcinoma, together with a genomic profiling of mutations occurring in a panel of genes relev…
Definitive evidence for Club cells as progenitors for mutantKras/Trp53‐deficient lung cancer
2021
Accumulating evidence suggests that both the nature of oncogenic lesions and the cell-of-origin can strongly influence cancer histopathology, tumor aggressiveness and response to therapy. Although oncogenic Kras expression and loss of Trp53 tumor suppressor gene function have been demonstrated to initiate murine lung adenocarcinomas (LUADs) in alveolar type II (AT2) cells, clear evidence that Club cells, representing the second major subset of lung epithelial cells, can also act as cells-of-origin for LUAD is lacking. Equally, the exact anatomic location of Club cells that are susceptible to Kras transformation and the resulting tumor histotype remains to be established. Here, we provide de…
A Multicenter Large Retrospective Database on the Personalization of Stereotactic Ablative Radiotherapy for Lung Metastases From Colon-Rectal Cancer:…
2021
PURPOSE/OBJECTIVE(S): stereotactic ablative radiotherapy (SABR) has been shown to increase survival rates in oligometastatic disease (OMD), but local control of colorectal metastases still remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate how lung SBRT can impact on the progression to the polymetastatic disease (PMD). MATERIALS/METHODS: the study involved 22 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1023 lung metastases treated with SBRT in 622 patients were reported. The median BED was 105 Gy10. Lesion diameter GTV, PTV volume, dose, fractionations, and site…
No evidence of EMAST in whole genome sequencing data from 248 colorectal cancers.
2021
Microsatellite instability (MSI) is caused by defective DNA mismatch repair (MMR), and manifests as accumulation of small insertions and deletions (indels) in short tandem repeats of the genome. Another form of repeat instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), has been suggested to occur in 50% to 60% of colorectal cancer (CRC), of which approximately one quarter are accounted for by MSI. Unlike for MSI, the criteria for defining EMAST is not consensual. EMAST CRCs have been suggested to form a distinct subset of CRCs that has been linked to a higher tumor stage, chronic inflammation, and poor prognosis. EMAST CRCs not exhibiting MSI have b…
Evolutionary convergence and nitrogen metabolism in Blattabacterium strain Bge, primary endosymbiont of the cockroach Blattella germanica.
2009
Bacterial endosymbionts of insects play a central role in upgrading the diet of their hosts. In certain cases, such as aphids and tsetse flies, endosymbionts complement the metabolic capacity of hosts living on nutrient-deficient diets, while the bacteria harbored by omnivorous carpenter ants are involved in nitrogen recycling. In this study, we describe the genome sequence and inferred metabolism of Blattabacterium strain Bge, the primary Flavobacteria endosymbiont of the omnivorous German cockroach Blattella germanica. Through comparative genomics with other insect endosymbionts and free-living Flavobacteria we reveal that Blattabacterium strain Bge shares the same distribution of functio…
Dermatux: Phase IV trial of C-FOLFIRI in 1st-line metastatic colorectal cancer receiving a pre-defined skin care.
2016
e15048Background: Dose- and treatment limiting cetuximab-induced skin rash ≥ 3° occur in 18% of colorectal cancer (CRC) patients. Survival, response and toxicity parameters were re-evaluated under a pre-defined skin prophylaxis consistent of vitamin K1 ointment and oral doxycycline. Methods: This is a national, phase IV, multicenter, 1st-line CRC trial (N = 165, KRAS wt, EGFR +, ECOG 0/1) in UICC stage 4 patients. Patients received irinotecan 180 mg/m² (d1) , folinic acid 400 mg/m² (d1), and 5-FU 400 mg/m² (d1, d2) and cetuximab ( 400 mg² (d1), then 250 mg/m² qw). Concurrently, patients received 0.1% vitamin K1 ointment qd and oral doxycycline 100 mg bid. Upon occurrence of rash ≥ 3°, an ad…
KRAS-G12C Mutation in One Real-Life and Three Population-Based Nordic Cohorts of Metastatic Colorectal Cancer
2022
Background: KRAS mutations, present in over 40% of metastatic colorectal cancer (mCRC), are negative predictive factors for anti-EGFR therapy. Mutations in KRAS-G12C have a cysteine residue for which drugs have been developed. Published data on this specific mutation are conflicting; thus, we studied the frequency and clinical characteristics in a real-world and population-based setting. Methods: Patients from three Nordic population-based cohorts and the real-life RAXO-study were combined. RAS and BRAF tests were performed in routine healthcare, except for one cohort. The dataset consisted of 2,559 patients, of which 1,871 could be accurately classified as KRAS, NRAS, and BRAF-V600E. Demog…
Eksperimentāla modeļa izstrāde neisseria gonorrhoeae antibakteriālas rezistences noteikšnai
2019
Neisseria gonorrhoeae infekcija mūsdienās ir globāla problēma. Latvijā tā ir otrā visbiežāk izplatītā bakteriālā seksuāli transmisīvā slimība. Mūsdienās satraucošā N. gonorrhoeae rezistence pret antibiotikām tiek atzīmēta visā pasaulē, tā ir padarījusi ārstēšanu nekomplicētai gonokoku infekcijai vēl sarežģītāku, ar mazāk ārstēšanas iespējām nekā agrāk. Visu laiku ārstiem pastāv jautājums, kā efektīvāk un ar maksimālu precizitāti noteikt antibakteriālo rezistenci. Tehnoloģijas nepārtraukti attīstās, tāpēc, teorētiski, pētījumi ar silīcija dioksīda mirkodaļiņām un to mijiedarbību ar mikroorganismiem varētu būt nozīmīgi antibakteriālās rezistences noteikšanai. Darba mērķis: Eksperimentāli note…
Tracing the fate of microplastic carbon in the aquatic food web by compound-specific isotope analysis
2019
Increasing abundance of microplastics (MP) in marine and freshwaters is currently one of the greatest environmental concerns. Since plastics are fairly resistant to chemical decomposition, breakdown and reutilization of MP carbon complexes requires microbial activity. Currently, only a few microbial isolates have been shown to degrade MPs, and direct measurements of the fate of the MP carbon are still lacking. We used compound-specific isotope analysis to track the fate of fully labelled 13C-polyethylene (PE) MP carbon across the aquatic microbial-animal interface. Isotopic values of respired CO2 and membrane lipids showed that MP carbon was partly mineralized and partly used for cell growt…