Duusbrantley1165
About 40% of
wild-type metastatic colorectal cancer (mCRC) patients undergoing anti-EGFR-based therapy have poor outcomes. Treatment failure is not only associated with poorer prognosis but higher healthcare costs. Our aim was to identify novel somatic genetic variants in the primary tumor and assess their effect on anti-EGFR response.
Tumor (somatic) and blood (germline) DNA samples were obtained from two well-defined cohorts of mCRC patients, those sensitive and those resistant to EGFR blockade. Genetic variant screening of 43 EGFR-related genes was performed using targeted next-generation sequencing (NGS). Relevant clinical data were collected through chart review to assess genetic results.
Among 61 patients, 38 were sensitive and 23 were resistant to treatment. CH4987655 We identified eight somatic variants that predicted non-response. Three were located in insulin-related genes (I668N and E1218K in
, T1156M in
) and three in genes belonging to the LRIG family (T152T in
, S697L in
and V812M in
). The remaining two variants were found in
(G115Efs*46) and
(T301T). We did not identify any somatic variants related to good response.
This study provides evidence that novel somatic genetic variants along the EGFR-triggered pathway could modulate the response to anti-EGFR drugs in mCRC patients. It also highlights the influence of insulin-related genes and
genes on anti-EGFR efficacy. Our findings could help characterize patients who are resistant to anti-EGFR blockade despite harboring
wild-type tumors.
This study provides evidence that novel somatic genetic variants along the EGFR-triggered pathway could modulate the response to anti-EGFR drugs in mCRC patients. It also highlights the influence of insulin-related genes and LRIG genes on anti-EGFR efficacy. Our findings could help characterize patients who are resistant to anti-EGFR blockade despite harboring RAS/BRAF wild-type tumors.
Intraoral scanners (IOSs) in implantology represent a viable approach for single teeth or partial arches. However, when used for complete edentulous arches or long-span edentulous areas, it has been demonstrated that there is a need for improvement of IOS-related techniques. Therefore, the aim of this in vitro study was to assess the trueness and precision of a complete arch digital impression on four and six implants taken with or without a customized, prosthetic-based impression template.
Two experimental models were prepared, representative of a complete edentulous mandible restored with four and six implants with built-in scan abutments. Models were scanned with (test group, TG) or without (control group, CG) the prosthetic-based impression template. Eight scans were taken for each model. The time needed to take impressions, error, trueness, and precision were evaluated. A statistical analysis was performed.
In the case of four implants, the time needed for the impression was 128.7 ± 55.3 s in the Tiginal model in the range of clinical acceptability, the prosthetic-based impression template significantly improved the trueness and precision of complete edentulous arches rehabilitated with four or six implants, making the complete arch digital impression more predictable.
Although all of the impressions exhibited deviation from the original model in the range of clinical acceptability, the prosthetic-based impression template significantly improved the trueness and precision of complete edentulous arches rehabilitated with four or six implants, making the complete arch digital impression more predictable.Developing antistatic long chain polyamide (LCPA) resins and fabricating the corresponding fuel pipes are challenges but necessary. Herein, a facile but effective strategy was put forward to fabricate LCPA resins with a superior conductivity, meeting the requirements of electrostatic sub-conductors. The strategy was based on, first, the incorporation of a large amount (15 wt%) of multi-walled carbon nanotubes (MWCNTs) into a polyamide 1012 (PA1012) matrix as a master batch, which formed a dense conductive network. Subsequently, it was diluted with PA1012 granules to produce base resins, and the reprocessed nanocomposites with a critical content of MWCNTs (3 wt%) could generate an effectively interconnected conductive network, with sparse and thinning features. Using the base resins, fuel pipes for automobiles, petrol stations and high pressure applications were successfully fabricated, where the thin conductive network was transformed into a thick one due to external field-induced re-agglomeration of MWCNTs. In this way, the obtained fuel pipes combined excellent conductive and barrier properties, and mechanical properties at high and low temperatures. These comprehensive properties also arose from the uniform dispersion of MWCNTs in an LCPA matrix, even without coupling agents; the attractive interaction between MWCNTs and the polyamide chains contributed to their strong interface adhesion. Thus, this research provides a versatile approach to fabricating antistatic LCPA resins, which will certainly extend their application to vehicle fuel systems.Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening dermatologic adverse events in the same category, caused by a delayed-type drug hypersensitivity reaction. Although skin toxicity is common during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib-associated TEN is quite rare-thus far, only one report has been published from China. We report a case of an 80-year-old Japanese woman with lung adenocarcinoma harboring an EGFR-sensitizing mutation who was treated with osimertinib as the first-line treatment. Forty-six days after osimertinib induction, diffuse erythematous rash rapidly spread over the patient's trunk along with vesicles and purpuric macules; furthermore, she developed targetoid erythema on the face. Despite osimertinib discontinuation and corticosteroid treatment, diffuse erythema with Nikolsky's sign, general epidermal detachment, erosion and loose blisters developed over her entire body including the face. Based on her symptoms, TEN was diagnosed and thus, intravenous immunoglobulin was immediately administered for 4 days.
