scholarly journals Patient-derived organoids as a platform for modeling a patient’s response to chemoradiotherapy in esophageal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatiana A. Karakasheva ◽  
Joel T. Gabre ◽  
Uma M. Sachdeva ◽  
Ricardo Cruz-Acuña ◽  
Eric W. Lin ◽  
...  

Abstract3D patient-derived organoids (PDOs) have been utilized to evaluate potential therapies for patients with different cancers. However, the use of PDOs created from treatment-naive patient biopsies for prediction of clinical outcomes in patients with esophageal cancer has not yet been reported. Herein we describe a pilot prospective observational study with the goal of determining whether esophageal cancer PDOs created from treatment naive patients can model or predict clinical outcomes. Endoscopic biopsies of treatment-naive patients at a single tertiary care center were used to generate esophageal cancer PDOs, which were treated with standard-of-care chemotherapy, gamma-irradiation, and newer non-standard approaches, such as proton beam therapy or two small molecule inhibitors. Clinical outcomes of patients following neoadjuvant treatment were compared to their in vitro PDO responses, demonstrating the PDO’s ability to mirror clinical response, suggesting the value of PDOs in prediction of clinical response to new therapeutic approaches. Future prospective clinical trials should test the use of pre-treatment PDOs to identify specific, targeted therapies for individual patients with esophageal adenocarcinoma.

2016 ◽  
Vol 7 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Vishwas D. Pai ◽  
Sudhir Jatal ◽  
Vikas Ostwal ◽  
Reena Engineer ◽  
Supreeta Arya ◽  
...  

2014 ◽  
Vol 58 (8) ◽  
pp. 4565-4572 ◽  
Author(s):  
Laura Judith Marcos-Zambrano ◽  
Pilar Escribano ◽  
Carlos Sánchez ◽  
Patricia Muñoz ◽  
Emilio Bouza ◽  
...  

ABSTRACTAccurate knowledge of fungemia epidemiology requires identification of strains to the molecular level. Various studies have shown that the rate of resistance to fluconazole ranges from 2.5% to 9% inCandidaspp. isolated from blood samples. However, trends in antifungal resistance have received little attention and have been studied only using CLSI M27-A3 methodology. We assessed the fungemia epidemiology in a large tertiary care institution in Madrid, Spain, by identifying isolates to the molecular level and performing antifungal susceptibility testing according to the updated breakpoints of European Committee for Antimicrobial Susceptibility Testing (EUCAST) definitive document (EDef) 7.2. We studied 613 isolates causing 598 episodes of fungemia in 544 patients admitted to our hospital (January 2007 to December 2013). Strains were identified after amplification and sequencing of the ITS1-5.8S-ITS2 region and further tested forin vitrosusceptibility to amphotericin B, fluconazole, posaconazole, voriconazole, micafungin, and anidulafungin. Resistance was defined using EUCAST species-specific breakpoints, and epidemiological cutoff values (ECOFFs) were applied as tentative breakpoints. Most episodes were caused byCandida albicans(46%),Candida parapsilosis(28.7%),Candida glabrata(9.8%), andCandida tropicalis(8%). Molecular identification enabled us to better detect cryptic species ofCandida guilliermondiiandC. parapsilosiscomplexes and episodes of polyfungal fungemia. The overall percentage of fluconazole-resistant isolates was 5%, although it was higher inC. glabrata(8.6%) and non-Candidayeast isolates (47.4%). The rate of resistance to echinocandins was 4.4% and was mainly due to the presence of intrinsically resistant non-Candidaspecies. Resistance mainly affected non-Candidayeasts. The rate of resistance to fluconazole and echinocandins did not change considerably during the study period.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 124-124
Author(s):  
Andrew M. Blakely ◽  
Andres Matoso ◽  
Thomas J. Miner

124 Background: The immune microenvironment is emerging as an important prognostic factor with potential therapeutic targets for various malignancies. Although programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) have been studied in some tumor types, significance of their expression in gastrointestinal stromal tumors (GISTs) is largely unknown. Methods: Tissue microarrays at an academic tertiary care center were constructed from pathology files from 1996 to 2016. Immunohistochemistry for PD-L1 and IDO was performed and correlated with tumor size, mitoses, and clinical outcomes. Tumor infiltrating lymphocytes (TILs) were counted using image analysis software. Results: 131 GISTs were analyzed. Median patient age was 64 years (range 30-89); 51.1% were male. Tumor location included 89 stomach (67.9%), 34 small bowel (26.0%), 4 colorectal (3.1%), and 4 other (3.1%). Median follow-up was 58 months. Mean tumor size was 5.6±4.5cm, range 0.5 to 24; mean mitoses were 7.2/50HPF. 19 (14.5%) metastasized to mesentery (n = 8), liver (n = 6), and elsewhere (n = 5). Mean survival was 61 months (range 7-127); 5 patients died of disease (3.8%). PD-L1 immunostain was positive in 89 (67.9%), including 11 of 19 (57.9%) malignant and 78 of 112 (69.6%) benign tumors (p = 0.4). PD-L1 positive tumors were larger (6.3±4.4 vs. 4.4±3.4 cm; p = 0.02) and had more mitoses/50HPF (8.9±5.4 vs. 3.9±3.5; p = 0.006) than PD-L1 negative tumors. IDO immunostain was positive in 116 (88.5%), including 14 of 19 (73.7%) malignant and 102 of 112 (91.1%) benign tumors (p = 0.07). There was no significant difference in size or mitotic count between IDO positive and negative tumors. Mean number of CD8-positive TILs was 168±35/mm2 and mean number of PD-L1 positive TILs was 147±28/mm2 in PD-L1 positive tumors. PD-L1 positive tumors had significantly more TILs than PD-L1 negative tumors (113±21 vs. 104±18; p < 0.001). Conclusions: The majority of GISTs express PD-L1 and IDO. Expression of PD-L1 was associated with increased tumor size and higher mitotic activity. PD-L1 and IDO could play a significant role in the tumor biology of GISTs; immunotherapy targeting one or both may provide novel treatment options.


2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Amar Ramachandran ◽  
Pratap Kumar ◽  
Naveen Manohar ◽  
Raviraj Acharya ◽  
Anita Eipe ◽  
...  

Ovarian hyperstimulation syndrome (OHSS) is a known complication of using ovulation induction drugs in assisted reproductive techniques. Its incidence and severity vary. Tuberculosis is a very common disease in the developing world, and ascites is one of its sequelae. The newer aids in diagnosing tuberculosis include measuring levels of Adenosine DeAminase (ADA) in the third-space fluids or serum. This case report is from a tertiary care center, reflecting how tubercular ascites simulated OHSS, and the right diagnosis was made and managed. This is being presented due to its rarity.


2021 ◽  
Vol 34 (2) ◽  
pp. 229-231
Author(s):  
Thomas Woodard ◽  
Lueke Anderson ◽  
Jessica Ehrig ◽  
Courtney Shaver ◽  
Michael Hofkamp

2021 ◽  
Vol 12 ◽  
Author(s):  
Vasudha Mantravadi ◽  
Jeffrey J. Bednarski ◽  
Michelle A. Ritter ◽  
Hongjie Gu ◽  
Ana L. Kolicheski ◽  
...  

The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting immunology findings of term infants referred to a tertiary care center with abnormal newborn SCID screens over a 6-year period. Key findings included a 33% incidence of non-SCID TCL including infants with novel variants in FOXN1, TBX1, MYSM1, POLD1, and CD3E; 57% positivity rate of newborn SCID screening among infants with DiGeorge syndrome; and earlier diagnosis and improved transplant outcomes for SCID in infants diagnosed after compared to before implementation of routine screening. Our study is unique in terms of the extensive laboratory workup of abnormal SCID screens including lymphocyte subsets, measurement of thymic output (TREC and CD4TE), and lymphocyte proliferation to mitogens in nearly all infants. These data allowed us to observe a stronger positive correlation of the absolute CD3 count with CD4RTE than with TREC copies, and a weak positive correlation between CD4RTE and TREC copies. Finally, we did not observe a correlation between risk of TCL and history of prenatal or perinatal complications or low birth weight. Our study demonstrated SCID newborn screening improves disease outcomes, particularly in typical SCID, and allows early detection and discovery of novel variants of certain TCL-associated genetic conditions.


IJID Regions ◽  
2021 ◽  
Author(s):  
Suvaporn Anugulruengkitt ◽  
Sirinya Teeraananchai ◽  
Napaporn Chantasrisawad ◽  
Pathariya Promsena ◽  
Watsamon Jantarabenjakul ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document