The fact that many chemotherapeutic drugs cause chemoresistance and side effects during the course of colorectal cancer treatment necessitates development of novel cytotoxic agents aiming to attenuate new molecular targets. Here, we show that Astragalus membranaceus (Fischer) Bge. var. mongolicus (Bge.) Hsiao (AM), a traditional Chinese medicine, can inhibit tumor growth in vivo and elucidate the underlying molecular mechanisms. The antitumor effect of AM was assessed on the subcutaneous tumors of human colorectal cancer cell line HCT116 grafted into nude mice. The mice were treated with either water or 500 mg/kg AM once per day, before being sacrificed for extraction of tumors, which were then subjected to microarray expression profiling. The gene expression of the extraction was then profiled using microarray analysis. The identified genes differentially expressed between treated mice and controls reveal that administration of AM suppresses chromosome organization, histone modification, and regulation of macromolecule metabolic process. A separate analysis focused on differentially expressed microRNAs revealing involvement of macromolecule metabolism, and intracellular transport, as well as several cancer signaling pathways. For validation, the input of the identified genes to The Library of Integrated Network-based Cellular Signatures led to many chemopreventive agents of natural origin that produce similar gene expression profiles to that of AM. The demonstrated effectiveness of AM suggests a potential therapeutic drug for colorectal cancer.
Background The three geriatric conditions, depression, dementia and delirium (3D’s), are common among hospitalized older patients and often lead to impairments of activities of daily living. The aim of this study is to explore the impact of depression, dementia and delirium on activities of daily living (ADLs) during and after hospitalization. Methods A prospective cohort study was conducted between 2012 and 2013 in a tertiary medical center in Taiwan. Patients who aged over 65 years and admitted to the geriatric ward were invited to this study. Geriatric Depression Scale Short Form, Mini-Mental State and Confusion Assessment Method were used to identify patients with depression, dementia and delirium on admission, respectively. Barthel Index (BI) was used to evaluate patients’ functional status on admission, at discharge, 30-day, 90-day and 180-day after discharge. Generalized Estimating Equation (GEE) was used to calculate the associations between 3 D’s and BI. Results One-hundred-and-forty-nine patients were included in this study. Twenty-seven patients (18.1%) had depression, 37 (24.8%) had dementia, and 85 (57.0%) had delirium. The study demonstrated that all the geriatric patients with functional decline presented gradual improvements of physical function up to 180 days after discharge. Whether depression exists did not substantially affect functional recovery after discharge, whilst either dementia or delirium could impede elder people functional status. The recovery of functional improvement in delirium or dementia was relatively irreversible when comparing with depression. Once delirium or dementia was diagnosed, poorer functional restore was expected. In brief, intensive work and strategies on modifying delirium or dementia should be put more effort as early as possible. Conclusions Old hospitalized patients with depression can recover well after adequate intervention. We emphasize that early detection of dementia and delirium is imperative in subsequent functional outcome, even if at or before admission. Comprehensive plan must be implemented timely.
Background The three geriatric conditions, depression, dementia and delirium (3D’s), are common among hospitalized older patients and often lead to impairments of activities of daily living. The aim of this study is to explore the impact of depression, dementia and delirium on activities of daily living (ADLs) during and after hospitalization. Methods A prospective cohort study was conducted between 2012 and 2013 in a tertiary medical center in Taiwan. Patients aged 65 years and older admitted to the geriatric ward were invited to this study. Geriatric Depression Scale Short Form, Mini-Mental State and Confusion Assessment Method were used to identify patients with depression, dementia and delirium on admission, respectively. Barthel Index (BI) was used to evaluate patients’ functional status on admission, at discharge, 30-day, 90-day and 180-day after discharge. Generalized Estimating Equation was used to calculate the associations between 3 D’s and BI. Results One-hundred-and-forty-nine patients were included in this study. Twenty-seven patients (18.1%) had depression, 37 (24.8%) had dementia, and 85 (57.0%) had delirium. There were significant lower BI scores in patients with dementia and delirium compared with those without up to 180 days after discharge, but no difference was seen in the depression group. In general, patients had delirium or dementia had worsening functional status, even though significant magnitude of improvements on BI scores after discharge. Conclusions Depression does not affect patients’ ADLs. On the other hand, dementia and delirium can persistently limit patients’ physical function. Future care should focus more on dementia and delirium to restore function.
The impact of the new International Association for the Study of Lung Cancer pathology committee grading system for advanced lung adenocarcinoma (LADC) on survival is unclear, especially in Asian populations. In this study, we reviewed the prognostic outcomes of patients with late-stage disease according to the new grading system. We reviewed 136 LADC cases who underwent a small biopsy from 2007 to 2018. Tumors were classified according to the new grading system for LADC. Baseline characteristics (age, sex, smoking status, body mass index, and driver gene mutations) were analyzed. Kaplan–Meier and Cox regression analyses were used to determine correlations with the new grading system and prognosis. Patients with poorly differentiated adenocarcinoma were significantly correlated with a poor progression-free survival (PFS) (p = 0.013) but not overall survival (OS) (p = 0.154). Subgroup analysis showed that wild-type EGFR patients with poorly differentiated adenocarcinoma treated with chemotherapy had significantly worse PFS (p = 0.011). There was no significant difference in survival among the patients with epidermal growth factor receptor mutations who were treated with tyrosine kinase inhibitors. Patients aged >70 years and those with a BMI ≤ 25 kg/m2 and wild-type patients had significantly worse OS in both univariate (HR = 1.822, p = 0.006; HR = 2.250, p = 0.004; HR = 1.537, p = 0.046, respectively) and multivariate analyses (HR = 1.984, p = 0.002; HR = 2.383, p = 0.002; HR = 1.632, p = 0.028, respectively). Despite therapy, patients with poorly differentiated tumors still fared worse than those with better differentiated tumors. No differences were found among the EGFR mutations treated with TKI. Our findings highlight that the therapeutic regimen should be adjusted for EGFR Wild-type patients with poorly differentiated adenocarcinoma treated with chemotherapy to provide better outcomes.
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