Triptolide is an extract from Tripterygium wilfordii used in traditional Chinese medicine to treat autoimmune disorders. Triptolide has anticancer effects in vitro and is reported to impair cancer ...cell migration. We studied whether triptolide inhibits lung cancer cell migration and metastasis.
We determined the microRNA expression profile of triptolide-treated cells. We tested the effects of triptolide treatment on migration and invasion of lung cancer cells by using Transwell filters coated with fibronectin and Matrigel, respectively. Western blot analyses were used to compare expression of proteins involved in cell migration before and after 10 nmol/L triptolide treatment. Tail vein injections with H358 cells were performed. The mice were treated with 1 mg/kg triptolide or vehicle by intraperitoneal injection three times per week. Lung and liver metastases were compared at 9 weeks. Means of groups were compared by using a t test.
Triptolide altered the expression of microRNAs involved in cellular movement and significantly decreased migration and invasion of lung cancer cells from approximately 18 to 3 cells per field (p < 0.001). Triptolide decreases focal adhesion kinase expression, which leads to impairment of downstream signaling. Finally, triptolide-treated mice injected with lung cancer cells significantly decreased metastatic colony formation in the lungs (p < 0.01).
Triptolide decreases lung cancer cell migration and invasion in vitro and inhibits metastatic tumor formation in mice. Triptolide suppresses focal adhesion kinase, which causes deregulation of the migration machinery. These results suggest that triptolide inhibits lung cancer metastasis and should be investigated as a new lung cancer therapy.
Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a ...comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients' smoking status, and the response to immunotherapy.
Abstract Context Palliative care, including symptom management and attention to quality of life (QOL) concerns, should be addressed throughout the trajectory of a serious illness such as lung cancer. ...Objectives This study tested the effectiveness of an interdisciplinary palliative care intervention for patients with Stage I–IV non–small cell lung cancer (NSCLC). Methods Patients undergoing treatments for NSCLC were enrolled in a prospective, quasi-experimental study whereby the usual care group was accrued first followed by the intervention group. Patients in the intervention group were presented at interdisciplinary care meetings, and appropriate supportive care referrals were made. They also received four educational sessions. In both groups, QOL, symptoms, and psychological distress were assessed at baseline and 12 weeks using surveys which included the Functional Assessment of Cancer Therapy–Lung and the Lung Cancer Subscale, the 12-item Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being, and the Distress Thermometer. Results A total of 491 patients were included in the primary analysis. Patients who received the intervention had significantly better scores for QOL (109.1 vs. 101.4; P < 0.001), symptoms (25.8 vs. 23.9; P < 0.001) spiritual well-being (38.1 vs. 36.2; P = 0.001), and lower psychological distress (2.2 vs. 3.3; P < 0.001) at 12 weeks, after controlling for baseline scores, compared to patients in the usual care group. Patients in the intervention group also had significantly higher numbers of completed advance care directives (44% vs. 9%; P < 0.001), and overall supportive care referrals (61% vs. 28%; P < 0.001). The benefits were seen primarily in the earlier stage patients vs. those with Stage IV disease. Conclusion Interdisciplinary palliative care in the ambulatory care setting resulted in significant improvements in QOL, symptoms, and distress for NSCLC patients.
Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer deaths. Lung cancer screening (LCS) reduces NSCLC mortality; however, a lack of diversity in LCS studies may limit the ...generalizability of the results to marginalized groups who face higher risk for and worse outcomes from NSCLC. Identifying sources of inequity in the LCS pipeline is essential to reduce disparities in NSCLC outcomes. The authors searched 3 major databases for studies published from January 1, 2010 to February 27, 2020 that met the following criteria: 1) included screenees between ages 45 and 80 years who were current or former smokers, 2) written in English, 3) conducted in the United States, and 4) discussed socioeconomic and race‐based LCS outcomes. Eligible studies were assessed for risk of bias. Of 3721 studies screened, 21 were eligible. Eligible studies were evaluated, and their findings were categorized into 3 themes related to LCS disparities faced by Black and socioeconomically disadvantaged individuals: 1) eligibility; 2) utilization, perception, and utility; and 3) postscreening behavior and care. Disparities in LCS exist along racial and socioeconomic lines. There are several steps along the LCS pipeline in which Black and socioeconomically disadvantaged individuals miss the potential benefits of LCS, resulting in increased mortality. This study identified potential sources of inequity that require further investigation. The authors recommend the implementation of prospective trials that evaluate eligibility criteria for underserved groups and the creation of interventions focused on improving utilization and follow‐up care to decrease LCS disparities.
Dysregulated histone methyltransferase G9a may represent a potential cancer therapeutic target. The roles of G9a in tumorigenesis and therapeutics are not well understood in non-small cell lung ...cancer (NSCLC). Here we investigated the impact of G9a on tumor growth and signaling pathways in NSCLC.
Immunohistochemistry analyzed G9a expression in NSCLC tissues. Both siRNA and selective inhibitor were used to target G9a. The impact of targeting G9a on key genes, signaling pathways and growth were investigated in NSCLC cells by RNA sequencing analysis, rescue experiments, and xenograft models.
Overexpression of G9a (≥ 5% of cancer cells showing positive staining) was found in 43.2% of 213 NSCLC tissues. Multiple tumor-associated genes including HP1α, APC2 are differentially expressed; and signaling pathways involved in cellular growth, adhesion, angiogenesis, hypoxia, apoptosis, and canonical Wnt signaling pathways are significantly altered in A549, H1299, and H1975 cells upon G9a knockdown. Additionally, targeting G9a by siRNA-mediated knockdown or by a selective G9a inhibitor UNC0638 significantly inhibited tumor growth, and dramatically suppressed Wnt signaling pathway in vitro and in vivo. Furthermore, we showed that treatment with UNC0638 restores the expression of APC2 expression in these cells through promoter demethylation. Restoring HP1α and silencing APC2 respectively attenuated the inhibitory effects on cell proliferation and Wnt signaling pathway in cancer cells in which G9a was silenced or suppressed.
These findings demonstrate that overexpressed G9a represents a promising therapeutic target, and targeting G9a potentially suppresses growth and Wnt signaling pathway partially through down-regulating HP1α and epigenetically restoring these tumor suppressors such as APC2 that are silenced in NSCLC.
Summary Background The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such ...patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. Methods A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I–III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). Findings Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5–80·0) in low-risk, 58·3% (48·9–66·6) in intermediate-risk, and 49·2% (42·2–55·8) in high-risk patients (ptrend =0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0–80·6) in low-risk, 57·4% (48·3–65·5) in intermediate-risk, and 44·6% (40·2–48·9) in high-risk patients (ptrend <0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. Interpretation Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. Funding UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
Liquid biopsy (LB) is clinically utilized to detect minute amounts of genetic material or protein shed by cancer cells, most commonly cell free DNA (cfDNA), as a noninvasive precision oncology tool ...to assess genomic alterations to guide cancer therapy or to detect the persistence of tumor cells after therapy. LB is also being developed as a multi-cancer screening assay. The use of LB holds great promise as a tool to detect lung cancer early. Although lung cancer screening (LCS) with low-dose computed tomography (LDCT) substantially reduces lung cancer mortality in high-risk individuals, the ability of current LCS guidelines to reduce the public health burden of advanced lung cancer through early detection has been limited. LB may be an important tool to improve early lung cancer detection among all populations at risk for lung cancer. In this systematic review, we summarize the test characteristics, including sensitivity and specificity of individual tests, as they pertain to the detection of lung cancer. We also address critical questions in the use of liquid biopsy for early detection of lung cancer including: 1. How might liquid biopsy be used to detect lung cancer early; 2. How accurate is liquid biopsy in detecting lung cancer early; and 3. Does liquid biopsy perform as well in never and light-smokers compared with current and former smokers.
Abstract Introduction Lung cancer screening (LCS) with low dose computed tomography (LDCT) reduces mortality and is recommended for high-risk current and former smokers. Several potential harms ...associated with LCS have been identified, including the potential for psychological burden. To summarize the current state of the scientific knowledge on psychological burden associated with LCS, we performed a systematic search of the contemporary quantitative and qualitative research literature. Methods We included randomized controlled trials and cohort studies that evaluated the impact of LCS with LDCT on psychological burden and health-related quality of life (HRQOL) as assessed by validated and non-validated measures. PubMed, CINAHL, PsychINFO, and Scopus were searched for English language articles published between 2004 and January 2015. Data abstraction and quality assessment were conducted by two independent reviewers. Results Thirteen studies were included that met our inclusion criteria. Overall, results were variable with some studies reporting worse psychological burden for patients with indeterminate results at pre-screening, post-screening and short-term follow-up (<6 months post-screen). These adverse effects diminished or resolved at long-term follow-up (>6 months post-screen). Conclusion LCS may be associated with short-term adverse psychological burden, particularly after a false positive result. However, these adverse effects diminished over time. The current evidence is small, with limitations in study design and use of outcome measures. More high-quality research is needed to determine the frequency, duration, and overall magnitude of LCS-related psychological burden in non-clinical trial settings.
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