The aim of this study was to evaluate whether stage at cancer diagnosis differed according to patient economic status.
A total of 10,528 patients with cancer of the stomach, colorectum, breast, or ...cervix, which are target organs of the Korean National Cancer Screening Program (NCSP; fully implemented in 2005) were extracted from population-based cancer registries. The patients were classified into four groups based on socioeconomic status (SES), as determined using their National Health Insurance (NHI) monthly premium at the time of cancer diagnosis. Cancer stage at diagnosis was defined as early (in situ/local) or late stage (regional/distant) based on the Surveillance, Epidemiology, and End Results (SEER) summary stage. Multivariable logistic regression analysis was performed to estimate the risk of non-local stage using age, residential area, and community deprivation index as covariates.
The lowest SES subjects showed significantly higher risks of being diagnosed at a later stage for stomach, colorectal, and female breast cancer, but not for cervical cancer, compared with the highest SES subjects. The estimated ORs were 1.28 (95% CI, 1.10–1.49), 1.29 (95% CI, 1.03–1.61), and 1.35 (95% CI, 1.02–1.81) in the lowest SES subjects with stomach, colorectal, and breast cancer, respectively.
In conclusion, later stage diagnoses of stomach, colon, and female breast cancer are still associated with SES in Korea in the era of the NCSP for the lower SES population.
•Advanced stage was more frequent in cancer patients with lower economic status.•Differences of stage by SES were found in stomach, colorectal, and breast cancer.•Disparities still exist after the National Cancer Screening program in Korea.
Although first-line crizotinib treatment leads to clinical benefit in
lung cancer, high prevalence of crizotinib-resistant ROS1-G2032R (ROS1
) mutation and progression in the central nervous system ...(CNS) represents a therapeutic challenge. Here, we investigated the antitumor activity of repotrectinib, a novel next-generation ROS1/TRK/ALK-tyrosine kinase inhibitor (TKI) in
patient-derived preclinical models.
Antitumor activity of repotrectinib was evaluated in
patient-derived preclinical models including treatment-naïve and ROS1
models and was further demonstrated in patients enrolled in an on-going phase I/II clinical trial (NCT03093116). Intracranial antitumor activity of repotrectinib was evaluated in a brain-metastasis mouse model.
Repotrectinib potently inhibited
and
tumor growth and ROS1 downstream signal in treatment-naïve YU1078 compared with clinically available crizotinib, ceritinib, and entrectinib. Despite comparable tumor regression between repotrectinib and lorlatinib in YU1078-derived xenograft model, repotrectinib markedly delayed the onset of tumor recurrence following drug withdrawal. Moreover, repotrectinib induced profound antitumor activity in the CNS with efficient blood-brain barrier penetrating properties. Notably, repotrectinib showed selective and potent
and
activity against ROS1
. These findings were supported by systemic and intracranial activity of repotrectinib observed in patients enrolled in the on-going clinical trial.
Repotrectinib is a novel next-generation ROS1-TKI with improved potency and selectivity against treatment-naïve and ROS1
with efficient CNS penetration. Our findings suggest that repotrectinib can be effective both as first-line and after progression to prior ROS1-TKI.
Background Despite many studies on endoplasmic reticulum (ER) stress in patients with various inflammatory diseases, there is scarce information on ER stress in patients with bronchial asthma. ...Objective In this study we aimed to elucidate the role of ER stress in the pathogenesis of bronchial asthma. Methods Using mice sensitized with ovalbumin (OVA) and LPS and challenged with OVA (OVALPS -OVA mice), as well as mice sensitized and challenged with OVA (OVA-OVA mice), we investigated whether ER stress is involved in the pathogenesis of bronchial asthma. Moreover, we also determined the levels of ER stress markers in blood and bronchoalveolar lavage fluid from asthmatic patients. Results The OVALPS -OVA mice showed that the expression of ER stress markers and the protein levels of unfolded protein response-related markers in lung tissue were significantly increased after OVA challenge. Moreover, we found that ER stress markers in PBMCs and bronchoalveolar lavage fluid from human asthmatic patients were dramatically increased compared with those from healthy control subjects. In OVALPS -OVA mice 4-phenylbutyric acid (4-PBA), a chemical chaperone, significantly reduced the increases in ER stress, nuclear translocation of nuclear factor κB, inflammatory cytokine levels, dendritic cell infiltration, Toll-like receptor 4 expression, airway inflammation, and bronchial hyperresponsiveness, whereas it further enhanced the increase in IL-10 levels. Additionally, the established asthmatic features of OVA-OVA mice were substantially attenuated by 4-PBA administered after completion of OVA challenge. Conclusion These results indicate that ER stress might be implicated in the pathogenesis of bronchial asthma at least in part through modulation of nuclear factor κB activation.
Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the ...disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC).
Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC
and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites.
The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC.
Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.
: This study was undertaken to investigate the antimicrobial effect of organic acids against Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes on whole red organic apples ...and lettuce. Several studies have been conducted to evaluate organic acids as sanitizers. However, no studies have compared antimicrobial effects of various organic acids on organic fresh produce, including evaluation of color changes of produce. Apples and lettuce were inoculated with a cocktail of 3 strains each of 3 foodborne pathogens provided above and treated with 1% and 2% organic acids (propionic, acetic, lactic, malic, and citric acid) for 0, 0.5, 1, 5, and 10 min. With increasing treatment time and acid concentration, organic acid treatments showed significant reduction compared to the control treatment (distilled water), and differences in antimicrobial effects between organic acids were observed. After 10 min of treatment with 1% and 2% organic acids in apples, propionic (0.92 to 2.75 log reduction), acetic (0.52 to 2.78 log reduction), lactic (1.69 to >3.42 log reduction), malic (1.48 to >3.42 log reduction), and citric acid (1.52 to >3.42 log reduction) exhibited significant (P < 0.05) antibacterial effects against 3 foodborne pathogens compared to the control treatment. In lettuce, propionic (0.93 to 1.52 log reduction), acetic (1.13 to 1.74 log reduction), lactic (1.87 to 2.54 log reduction), malic (2.32 to 2.98 log reduction), and citric acid (1.85 to 2.86 log reduction) showed significant (P < 0.05) effects compared to the control treatment. Changes in sample color subjected to organic acids treatment were not significant during storage.
Practical Application: It is suggested that organic acids have a potential as sanitizers for organic fresh produce. These data may help the organic produce industry provide safe fresh produce for consumers.
Background
With advances in surgical technique and instrumentation, intracorporeal anastomosis is increasingly being performed for laparoscopic total gastrectomy (LTG). However, the benefits of ...intracorporeal anastomosis in reducing postoperative complications have not been demonstrated, although its technical feasibility has been proven in many studies. In this study, we investigated the impact of intracorporeal anastomosis in reducing postoperative complications after LTG.
Methods
We analyzed 410 consecutive gastric cancer patients who underwent LTG between 2008 and 2018. Of these, 118 underwent intracorporeal anastomosis using linear staplers (overlap method), while 292 underwent extracorporeal anastomosis using a circular stapler. Short-term surgical outcomes including postoperative complications were compared between the two groups.
Results
The two groups showed no significant differences in age, sex, comorbidity, and abdominal surgery history. D2 lymph node dissection was more frequently performed in the intracorporeal group because of the presence of more advanced cancer stages. The overall morbidity in the intracorporeal and extracorporeal group was 23.7% and 27.7%, respectively (
p
= 0.405). However, the intracorporeal group showed a significantly lower incidence of late complications (0.8% vs. 7.5%,
p
= 0.008). Concerning complications, the incidence of anastomotic bleeding (0% vs. 5.5%,
p
= 0.008) and anastomotic stenosis (0% vs. 4.5%,
p
= 0.024) was significantly lower in the intracorporeal group. In univariate and multivariate analyses, American Society of Anesthesiologists score and operative bleeding were independent predictive factors for postoperative complications in patients who underwent intracorporeal anastomosis.
Conclusions
Intracorporeal anastomosis using linear staplers reduced anastomotic bleeding and stenosis compared to extracorporeal anastomosis after LTG. Future research will be required to determine the ideal method for intracorporeal anastomosis in LTG.
RATIONALE:Peroxiredoxin 2 (Prdx2), a thiol-specific peroxidase, has been reported to regulate proinflammatory responses, vascular remodeling, and global oxidative stress.
OBJECTIVE:Although Prdx2 has ...been proposed to retard atherosclerosis development, no direct evidence and mechanisms have been reported.
METHODS AND RESULTS:We show that Prdx2 is highly expressed in endothelial and immune cells in atherosclerotic lesions and blocked the increase of endogenous H2O2 by atherogenic stimulation. Deficiency of Prdx2 in apolipoprotein E–deficient (ApoE) mice accelerated plaque formation with enhanced activation of p65, c-Jun, JNKs, and p38 mitogen-activated protein kinase; and these proatherogenic effects of Prdx2 deficiency were rescued by administration of the antioxidant ebselen. In bone marrow transplantation experiments, we found that Prdx2 has a major role in inhibiting atherogenic responses in both vascular and immune cells. Prdx2 deficiency resulted in increased expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1, which led to increased immune cell adhesion and infiltration into the aortic intima. Compared with deficiency of glutathione peroxidase 1 or catalase, Prdx2 deficiency showed a severe predisposition to develop atherosclerosis.
CONCLUSIONS:Prdx2 is a specific peroxidase that inhibits atherogenic responses in vascular and inflammatory cells, and specific activation of Prdx2 may be an effective means of antiatherogenic therapy.
Background
Since the eighth American Joint Committee on Cancer (AJCC) classification recently introduced the clinical classification for preoperative staging of gastric cancer, the new clinical ...classification has not been extensively validated yet. Therefore, in this study, we compared the prognostic performance of the new clinical classification and the pathologic classification for preoperative staging of gastric cancer.
Methods
We reviewed 3027 patients with gastric cancer who were surgically treated between 2009 and 2013. Patient survival was analyzed according to the preoperative stage by the clinical classification and the pathologic classification in the eighth AJCC classification. The prognostic performance was examined using the Akaike information criterion (AIC) value and Harrell
c
-index.
Results
Patient survival was significantly different across the different stages when both classifications were used. However, individual pairwise comparisons showed that survival differences between each stage were more distinctive and homogeneous in the pathologic classification. In the multivariate model adjusted for the final pathologic stage, preoperative staging by the pathologic classification was an independent prognostic factor, whereas the clinical classification was not. The pathologic classification showed a lower AIC value compared with the clinical classification (5100.64 vs. 5114.14). The Harrell
c
-index was higher in the pathologic classification than in the clinical classification (0.741 vs. 0.739).
Conclusions
The new clinical classification in the eighth AJCC classification discriminates patient survival well. However, it does not appear to have a better prognostic performance compared with the pathologic classification for preoperative staging of gastric cancer.
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