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Patient-derived organoids as a platform for modeling a patient's response to chemoradiotherapy in esophageal cancer.
Karakasheva, TA, Gabre, JT, Sachdeva, UM, Cruz-Acuña, R, Lin, EW, DeMarshall, M, Falk, GW, Ginsberg, GG, Yang, Z, Kim, MM, et al
Scientific reports. 2021;(1):21304
Abstract
3D 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.
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Genetic Predisposition to Colon and Rectal Adenocarcinoma Is Mediated by a Super-enhancer Polymorphism Coactivating CD9 and PLEKHG6.
Ke, J, Tian, J, Mei, S, Ying, P, Yang, N, Wang, X, Zou, D, Peng, X, Yang, Y, Zhu, Y, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2020;(4):850-859
Abstract
BACKGROUND Genome-wide association studies (GWAS) have identified dozens of loci associated with colon and rectal adenocarcinoma risk. As tissue-specific super-enhancers (SE) play important roles in tumorigenesis, we systematically investigate SEs and inner variants in established GWAS loci to decipher the underlying biological mechanisms. METHODS Through a comprehensive bioinformatics analysis on multi-omics data, we screen potential single-nucleotide polymorphisms (SNP) in cancer-specific SEs, and then subject them to a two-stage case-control study containing 4,929 cases and 7,083 controls from the Chinese population. A series of functional assays, including reporter gene assays, electrophoretic mobility shift assays (EMSA), CRISPR-Cas9 genome editing, chromosome conformation capture (3C) assays, and cell proliferation experiments, are performed to characterize the variant's molecular consequence and target genes. RESULTS The SNP rs11064124 in 12p13.31 is found significantly associated with the risk of colon and rectal adenocarcinoma with an odds ratio (OR) of 0.87 [95% confidence interval (CI), 0.82-0.92, P = 8.67E-06]. The protective rs11064124-G weakens the binding affinity with vitamin D receptor (VDR) and increases the enhancer's activity and interactions with two target genes' promoters, thus coactivating the transcription of CD9 and PLEKHG6, which are both putative tumor suppressor genes for colon and rectal adenocarcinoma. CONCLUSIONS Our integrative study highlights an SE polymorphism rs11064124 and two susceptibility genes CD9 and PLEKHG6 in 12p13.31 for colon and rectal adenocarcinoma. IMPACT These findings suggest a novel insight for genetic pathogenesis of colon and rectal adenocarcinoma, involving transcriptional coactivation of diverse susceptibility genes via the SE element as a gene regulation hub.
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Enhanced recovery after surgery in gastric cancer: which are the main achievements from the Italian experience?
Fumagalli Romario, U, Weindelmayer, J, Coratti, A, Cossu, A, Gianotti, L, Rausei, S, Sansonetti, A, De Pascale, S, ,
Updates in surgery. 2018;(2):257-264
Abstract
In the last years, the concept of 'enhanced recovery after surgery' (ERAS) has become a routine in the perioperative care of patients undergoing colorectal resection. The application of ERAS programs in gastric surgery had a more difficult penetration into clinical practice, mainly for the introduction of radical changes in the traditional postoperative management. The aim of the study was to analyze the rate of compliance to a standardized ERAS protocol in different Italian centers and evaluate the results in terms of postoperative outcomes. From April 2015 to July 2017, a prospective observational study was conducted among seven centers participating in the Italian Group for Research for Gastric Cancer (GIRCG), in patient candidates to elective gastrectomy for cancer. A standardized ERAS perioperative protocol was approved by all centers. Compliance to the protocol was then evaluated and postoperative outcomes (morbidity and mortality rate, duration of hospital stay and readmission rate) were analyzed. Two-hundred and seventy unselected patients operated on for gastric cancer were enrolled. The median age was 73 years; 40.4% of patients were female; 24.1% had a nutritional risk score ≥ 3. Perioperative chemotherapy was used in 23.7% of cases. Total gastrectomy was performed in 57.4% of patients; minimally invasive approach was adopted in 28.1% of patients. Adherence to the protocol varied between 23 and 88% for single items. It was quite low for pre- and intraoperative items, mainly for items related to nutritional care. Postoperative complications occurred in 35.5% of patients, mortality was 0.7%. Median length of hospital stay was 8 days (range 4-72) and the readmission rate was 6.3%. There is a growing attention on the implementation of ERAS protocol for gastric cancer surgery, but several elements of this protocol are still not routinely adopted, among them items regarding nutritional care.
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Recovery of Food Intake after Gastrectomy for Gastric Cancer: Based on a Large-Scale Gastric Cancer Cohort.
Eom, BW, Kim, J, Kim, DH, Kim, YI, Yoon, HM, Cho, SJ, Lee, JY, Kim, CG, Choi, IJ, Kim, YW, et al
Digestive surgery. 2018;(3):220-229
Abstract
BACKGROUND This study was aimed at evaluating the food intake and nutritional status of patients who underwent gastrectomy for gastric cancer based on a large-scale gastric cancer cohort. METHODS An observational prospective cohort study for gastric cancer has been conducted since 2010. From the cohort data, we selected the data for patients who completed at least 2 days of 3-day diet diaries and who underwent subtotal gastrectomy (STG) or total gastrectomy (TG). As a control group, patients who underwent endoscopic submucosal dissection were also included. The collected diet data were converted to macro- and micronutrients using computerized software, and the nutrient intakes were compared. RESULTS Among 6,556 patients who participated in the cohort study from 2011 to 2016, 1,289 patients who completed at least 2 days of 3-day diet diaries were included in this study. During the postoperative 3-month period, body weight was significantly decreased in the and TG groups. However, there was no difference in nutrient intake among the 3 groups except vitamin D and calcium intake. Similar results were observed during the postoperative 12 months period. CONCLUSIONS Postoperative body weight loss and anemia might originate from altered absorptive function and metabolic change after gastrectomy rather than decreased nutrient intake.
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Birth rates after radioactive iodine treatment for differentiated thyroid cancer.
Anderson, C, Engel, SM, Weaver, MA, Zevallos, JP, Nichols, HB
International journal of cancer. 2017;(11):2291-2295
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Abstract
Treatment with radioactive iodine (RAI) for differentiated thyroid cancer has been associated with alterations in gonadal function in women, including changes in menstrual function and an earlier age at menopause. Our objective was to evaluate associations between RAI and postdiagnosis live birth rates among thyroid cancer survivors diagnosed at ages 15-39 years. We identified women diagnosed with differentiated thyroid cancer between January 2000 and December 2013 in the North Carolina Central Cancer Registry (CCR). CCR records were linked to state birth certificate files to identify livebirths to thyroid cancer survivors through December 2014. Person-years of follow-up were accrued from 6 months after diagnosis to first birth, 46th birthday, death, or December 31, 2014, whichever came first. Cox proportional hazards regression was used to estimate hazards ratios (HR) and 95% confidence intervals (CI) for first livebirth. Among 2,360 women with a differentiated thyroid cancer diagnosis, 53% received RAI. The cumulative incidence of birth at the end of follow-up (maximum 14.5 years) was 30.0 and 29.3% among those who were and were not treated with RAI, respectively. Overall, first birth rates did not significantly differ between groups (HR = 1.00; 95% CI: 0.82, 1.23). In our observational cohort, treatment with RAI was not associated with a reduced birth rate. Our findings add to the evidence available for counseling thyroid cancer patients with concerns about future fertility.
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[Nab-Paclitaxel plus gemcitabine in patients with metastatic pancreatic adenocarcinoma: experience of use].
Ferris Villanueva, E, Martínez Penella, M, Cerezuela Fuentes, P, Guerrero Bautista, R, García Márquez, A, Mira Sirvent, Mdel C
Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria. 2015;(3):181-5
Abstract
OBJECTIVE To evaluate the results obtained with the combined use of nab-paclitaxel and gemcitabine in the treatment of patients with metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS Retrospective observational study. Patients treated with nab-paclitaxel and gemcitabine between January of 2013 and January of 2014 were selected. Demographical and clinical data were gathered. RESULTS 15 patients (mean age 59,4 ± 10,3 years) were included. All patients received the combination of nab-paclitaxel and gemcitabine in first-line metastatic disease. Nine received adjuvant treatment before the disease was metastatic. The median progression-free survival rate with combined nab-paclitaxel and gemcitabine was 5,6 months (95% CI: 4,44 - 8,03). In two patients the treatment was stopped due to toxicity. CONCLUSIONS The treatment with nab-paclitaxel and gemcitabine in our patients resulted in progression-free survival rates similar to those published in clinical trials with good treatment tolerability.