Prospective Observational Study of 1st and 2nd Line Vectibix Use in RAS-wt mCRC Pts to Evaluate Pattern of Use and ORR
Ontology highlight
ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2180719 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:This non-interventional retrospective medical record review study will assess the prevalence of KRAS testing and the impact of the KRAS test result on patterns of Vectibix use in patients with metastatic colorectal cancer (mCRC) treated with Vectibix in selected European countries over 3 rounds. As the optimal use of Vectibix also requires accurate KRAS mutation testing, this study will also assess data from the laboratory that performed the KRAS test. The study will also monitor changes in the pattern of Vectibix treatment between the different rounds of the study.
| 2140053 | ecrin-mdr-crc
Project description:Tarsometatarsal joint arthrodesis is used to treat a variety of injuries and deformities in the midfoot. However, the surgical technique has not been optimized, in part due to limited knowledge of morphologic features and variation in the related joints. Previous research has relied primarily on dissection-based anatomical analysis, but quantitative imaging may allow for a more sophisticated description of this complex. Here, we used quantitative micro-CT imaging to examine dimensions, distance maps, and curvature of the four articular surfaces in the first and second tarsometatarsal joints. Image segmentation, articular surface identification, and anatomic coordinate systems were all done with semi or fully automatic methods, and distance and size measurements were all taken utilizing these anatomic planes. Surface curvature was studied using Gaussian curvature and a newly defined measure of curvature similarity on the whole joint and on four subregions of each surface. These data show larger articular surfaces on the cuneiforms, rather than metatarsals, and define the generally tall and narrow articular surfaces seen in these joints. Curvature analysis shows minimally curved opposing convex surfaces. Our results are valuable for furthering knowledge of surgical anatomy in this poorly understood region of the foot.
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Project description:Over the past decade, immunotherapy has become an increasingly fundamental modality in the treatment of cancer. The positive impact of immune checkpoint inhibition, especially anti-programmed death (PD)-1/PD-ligand (L)1 blockade, in patients with different cancers has focused attention on the potential for other immunotherapeutic approaches. These include inhibitors of additional immune checkpoints, adoptive cell transfer (ACT), and therapeutic vaccines. Patients with advanced cancers who previously had limited treatment options available may now benefit from immunotherapies that can offer durable responses and improved survival outcomes. However, despite this, a significant proportion of patients fail to respond to immunotherapy, especially those with less immunoresponsive cancer types, and there remains a need for new treatment strategies.The virtual Immunotherapy Bridge (December 1st-2nd, 2021), organized by the Fondazione Melanoma Onlus, Naples, Italy in collaboration with the Society for Immunotherapy of Cancer addressed several areas of current research in immunotherapy, including lessons learned from cell therapies, drivers of immune response, and trends in immunotherapy across different cancers, and these are summarised here.
| S-EPMC9172186 | biostudies-literature
Project description:After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply interrogate longitudinal tissue in order to gain translatable, pan-malignancy insights into response and mechanisms of resistance to immunotherapy. Neoadjuvant immunotherapy across cancers was a focus of discussion at the virtual Immunotherapy Bridge meeting (December 1-2, 2021). Clinical, biomarker, and pathologic insights from prostate, breast, colon, and non-small-cell lung cancers, melanoma and non-melanoma skin cancers were discussed and are summarized in this report.
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Project description:PurposeTo investigate prediction of age older than 18 years in sub-adults using tooth tissue volumes from MRI segmentation of the entire 1st and 2nd molars, and to establish a model for combining information from two different molars.Materials and methodsWe acquired T2 weighted MRIs of 99 volunteers with a 1.5-T scanner. Segmentation was performed using SliceOmatic (Tomovision©). Linear regression was used to analyse the association between mathematical transformation outcomes of tissue volumes, age, and sex. Performance of different outcomes and tooth combinations were assessed based on the p-value of the age variable, common, or separate for each sex, depending on the selected model. The predictive probability of being older than 18 years was obtained by a Bayesian approach using information from the 1st and 2nd molars both separately and combined.Results1st molars from 87 participants, and 2nd molars from 93 participants were included. The age range was 14-24 years with a median age of 18 years. The transformation outcome (high signal soft tissue + low signal soft tissue)/total had the strongest statistical association with age for the lower right 1st (p= 7.1*10-4 for males) and 2nd molar (p=9.44×10-7 for males and p=7.4×10-10 for females). Combining the lower right 1st and 2nd molar in males did not increase the prediction performance compared to using the best tooth alone.ConclusionMRI segmentation of the lower right 1st and 2nd molar might prove useful in the prediction of age older than 18 years in sub-adults. We provided a statistical framework to combine the information from two molars.
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Project description:BACKGROUND:Superoxide generated by non-phagocytic NADPH oxidases (NOXs) is of growing importance for physiology and pathobiology. The calcium binding domain (CaBD) of NOX5 contains four EF-hands, each binding one calcium ion. To better understand the metal binding properties of the 1st and 2nd EF-hands, we characterized the N-terminal half of CaBD (NCaBD) and its calcium-binding knockout mutants. RESULTS:The isothermal titration calorimetry measurement for NCaBD reveals that the calcium binding of two EF-hands are loosely associated with each other and can be treated as independent binding events. However, the Ca2+ binding studies on NCaBD(E31Q) and NCaBD(E63Q) showed their binding constants to be 6.5 × 105 and 5.0 × 102 M-1 with ?Hs of -14 and -4 kJ/mol, respectively, suggesting that intrinsic calcium binding for the 1st non-canonical EF-hand is largely enhanced by the binding of Ca2+ to the 2nd canonical EF-hand. The fluorescence quenching and CD spectra support a conformational change upon Ca2+ binding, which changes Trp residues toward a more non-polar and exposed environment and also increases its ?-helix secondary structure content. All measurements exclude Mg2+-binding in NCaBD. CONCLUSIONS:We demonstrated that the 1st non-canonical EF-hand of NOX5 has very weak Ca2+ binding affinity compared with the 2nd canonical EF-hand. Both EF-hands interact with each other in a cooperative manner to enhance their Ca2+ binding affinity. Our characterization reveals that the two EF-hands in the N-terminal NOX5 are Ca2+ specific. GRAPHICAL
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Project description:Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m2 weekly) or flat-dose capecitabine (2000 mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays). The secondary endpoint is efficacy (week 12 objective response). Exploratory aims are to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. The trial demonstrates that both regimens meet the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate is 29% for pembrolizumab/paclitaxel (n = 4/13, 95% CI: 10-61%) and 43% for pembrolizumab/capecitabine (n = 6/14, 95% CI: 18-71%). Partial responses are observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens are associated with significant peripheral leukocyte contraction over time. Response is associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor-infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). In conclusion, pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens are lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted. The clinical trial registration is NCT02734290.
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Project description:Memory B cells play essential roles in the maintenance of long-term immunity and may be important in the pathogenesis of autoimmune disease, but how these cells are distinguished from their naïve precursors is poorly understood. To address this, it would be important to understand how gene expression differs between memory and naive B cells in order to elucidate memory-specific functions. Using model systems that help overcome the lack of murine memory-specific markers and the low frequency of antigen-specific memory and naïve cells, we undertook a global comparison of gene expression between memory B cells and their naive precursors. 1st generation screen: These data represent our first generation comparison of gene expression between murine naïve and memory splenic B cells. Naïve NP-binding splenic B cells were FACS purified from unimmunized mVh186.2 transgenic Balb/c mice. Memory B cells were generated by immunizing mVh186.2 transgenic Balb/c mice with 2 doses of NP-CGG in alum delivered i.p. 6 weeks apart. After a minimum of 12-weeks rest, NP-binding splenic B cells were isolated by FACS. Total RNA was extracted, cRNA synthesized and labeled and hybridized to Affymetrix mouse 430 2.0 chips. 2nd generation screen: These data represent our second generation comparison of gene expression between murine naïve and memory splenic B cells. Naïve NP-binding AA4.1neg splenic B cells were FACS purified from unimmunized mVh186.2 transgenic Jk KO Balb/c mice. Memory B cells were generated from these naive precursors after adoptive transfer into recipients that mount poor endogenous NP-responses. 12-weeks post i.p. immunization with NP-CGG in alum, NP-specific splenic memory B cells were isolated by FACS. Total RNA was extracted, cRNA synthesized and labeled and hybridized to Affymetrix mouse 430 2.0 chips. Memory/Naïve comparison data linked below as Supplementary files. Keywords: Cell type comparison
2008-06-05 | GSE11386 | GEO
Project description:Epigenetics may play a central, but yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy. We investigated changes in the methylome in isolated circulating CD4+ T cells in non-pregnant and pregnant women, during the 1st and 2nd trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with thousands of methylation differences, particularly during the 2nd trimester, where the majority of sites were hypermethylated, indicating transcriptional repression. Using a network-based modular approach disclosed several genes and pathways related to T cell signalling and activation. The pregnancy module was significantly enriched for disease-associated methylation changes related to multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. The directionality of the changes was also in line with the previously observed effect of pregnancy on the disease activity, with a negative correlation for multiple sclerosis and rheumatoid arthritis that improves during pregnancy, and a positive correlation for systemic lupus erythematosus, a disease that instead worsens. In summary, this systems medicine approach supports the importance of the methylome in immune regulation of CD4+ T cells during pregnancy. Samples included twelve (n=12) non-pregnant women, elven (n=11) 1st trimester pregnant women and twelve (n=12)
2022-06-06 | GSE153459 | GEO
Project description:PurposeWe aimed to establish a model combining MRI volume measurements from the 1st, 2nd and 3rd molars for age prediction in sub-adults and compare the age prediction performance of different combinations of all three molars, internally in the study cohort.Material and methodWe examined 99 volunteers using a 1.5 T MR scanner with a customized high-resolution single T2 sequence. Segmentation was performed using SliceOmatic (Tomovision©). Age prediction was based on the tooth tissue ratio (high signal soft tissue + low signal soft tissue)/total. The model included three correlation parameters to account for statistical dependence between the molars. Age prediction performance of different combinations of teeth for the three molars was assessed using interquartile range (IQR).ResultsWe included data from the 1st molars from 87 participants (F/M 59/28), 2nd molars from 93 (F/M 60/33) and 3rd molars from 67 (F/M 45/22). The age range was 14-24 years with a median age of 18 years. The model with the best age prediction performance (smallest IQR) was 46-47-18 (lower right 1st and 2nd and upper right 3rd molar) in males. The estimated correlation between the different molars was 0.620 (46 vs. 47), 0.430 (46 vs. 18), and 0.598 (47 vs. 18). IQR was the smallest in tooth combinations including a 3rd molar.ConclusionWe have established a model for combining tissue volume measurements from the 1st, 2nd and 3rd molars for age prediction in sub-adults. The prediction performance was mostly driven by the 3rd molars. All combinations involving the 3rd molar performed well.
| S-EPMC11003927 | biostudies-literature