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doi:10.18632/oncotarget.v8i44

Cited by 8 publications

(3 citation statements)

References 45 publications

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“…22 Notably, recent studies showed that KRT8 is also involved in tumor progress. KRT8 up-regulation promoted renal cell carcinoma metastasis via IL-11/STAT3 pathway, 23 enhanced migration of gastric cancer cells through TGF-β pathway. 24 In contrast, some studies indicated that KRT8 inhibit tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 98%

<p>The Metastasis Potential Promoting Capacity of Cancer-Associated Fibroblasts Was Attenuated by Cisplatin via Modulating KRT8</p>

Song¹,

Guo²,

Wang³

et al. 2020

OTT

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Background: Cancer-associated fibroblasts (CAFs) are an essential component of tumor microenvironment. They are attracting increasing attentions due to their crucial role in tumor growth, drug-resistance and metastasis. Cisplatin is a first-line chemotherapy drug applying in various types of cancer. There are intensive studies on cisplatin's effect on tumor cells, however, its effect on CAFs remains poorly understood. In the present study, we investigated the effect of cisplatin on CAFs. Methods: Cell migration was detected by wound healing assay. Cell invasion was performed by the transwell assay. mRNA expression was detected by quantitative PCR, and protein expression was detected by Western blotting. Tumor growth was measured using BALB/c nude mice tumor models. Results: Cisplatin attenuated the promoting capacity of CAFs on lung cancer cell migration and invasion, via suppressing CAFs' effect on metastasis-related genes including Twist1, vascular endothelial growth factor receptor (VEGFR), MMP2, and AKT signaling pathway. Keratin 8 (KRT8) was identified as a target of cisplatin. KRT8 upregulation in CAFs is responsible for the inhibitory effect of cisplatin on lung cancer cells metastasis potential through AKT pathway suppression. The stimulation of AKT by AKT activator SC79 reversed KRT8's effect on cell migration. Importantly, in vivo study also showed that CAFs enhanced tumor growth significantly, and cisplatin effectively abrogated the promoting effect of CAFs on tumor growth. Conclusion: Our results revealed a novel mechanism that cisplatin attenuated the metastasis promoting effect of CAFs via KRT8/AKT signaling pathway. This finding highlights KRT8 in CAFs as a potential therapeutic candidate for metastasis treatment.

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Section: Discussionmentioning

confidence: 98%

<p>The Metastasis Potential Promoting Capacity of Cancer-Associated Fibroblasts Was Attenuated by Cisplatin via Modulating KRT8</p>

Song¹,

Guo²,

Wang³

et al. 2020

OTT

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“…The Idylla TM MSI Assay from Biocartis (Mechelen, Belgium) was used according to the manufacturer's instructions to determine whether tumors were MSS or MSI. In 56 of the 92 cases, isolated DNA was available from CLM samples as previously described, 13 while in 36 cases, formalin-fixed tissue was used (31 from study CLM resections and 5 using tissue from the pCRC sample, where the CLM sample contained <10% tumor tissue).…”

Section: Analysis Of Msimentioning

confidence: 99%

“…[10][11][12] In a cohort of CLM resected after neoadjuvant chemotherapy (NACT) we recently identified transcriptional changes that are part of canonical pathways related to immune activation, such as natural killer cell signaling, dendritic cell maturation, leukocyte migration, and danger signaling through pattern recognition receptors. 13 Furthermore, in a study of locally advanced rectal cancer, we observed that increased serum levels of inducer of dendritic cell maturation, fms-like tyrosine kinase 3 ligand (Flt3L), were detected after administration of NACT. 14,15 These observations could indicate the occurrence of ICD upon NACT exposure.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant chemotherapy is associated with a transient increase of intratumoral T-cell density in microsatellite stable colorectal liver metastases

Dagenborg

Marshall

Yaqub

et al. 2020

Cancer Biology & Therapy

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Patients with colorectal liver metastases (CLM) commonly receive neoadjuvant chemotherapy (NACT) prior to surgical resection. NACT may induce immunogenic cell death with subsequent recruitment of T-cells to the tumor microenvironment, which could be exploited by immune checkpoint inhibition (ICI). In theory, this could expand the use of ICI to obtain responses also in microsatellite stable colorectal cancer, but evidence to suggest optimal treatment schedules are lacking. In this study, densities of total-, cytotoxic-, helper- and regulatory T-cells were quantified by immunohistochemistry in resected CLM from 92 patients included in the OSLO-COMET trial (NCT01516710). All but one patient had microsatellite stable tumors (91/92). Associations between T-cell densities and clinicopathological parameters were analyzed. Fluoropyrimidine-based NACT (in most cases with addition of oxaliplatin or irinotecan) was administered to 45 patients completed median 8 weeks prior to surgical resection. No overall association was found between NACT administration and intratumoral T-cell densities. However, within the NACT group, a short time interval (<9.5 weeks) between NACT completion and CLM resection was strongly associated with high intratumoral T-cell densities compared to the long-interval and no NACT groups (medians 491, 236, and 292 cells/mm 2 , respectively; P < .0001). The results from this study suggest that the observed increase in intratumoral T-cells after NACT administration may be transient. The significance of this finding should be further explored to ensure that optimal treatment schedules are chosen for studies combining cytotoxic chemotherapy and ICI.

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Evaluation of a Low-Dose Computed Tomography Lung Cancer Screening Program in Henan, China

et al. 2020

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IMPORTANCE Lung cancer screening has been widely implemented in Europe and the US. However, there is little evidence on participation and diagnostic yields in population-based lung cancer screening in China. OBJECTIVE To assess the participation rate and detection rate of lung cancer in a population-based screening program and the factors associated with participation. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used data from the Cancer Screening Program in Urban China from October 2013 to October 2019, with follow-up until March 10, 2020. The program is conducted at centers in 8 cities in Henan Province, China. Eligible participants were aged 40 to 74 and were evaluated for a high risk for lung cancer using an established risk score system. MAIN OUTCOMES AND MEASURES Overall and group-specific participation rates by common factors, such as age, sex, and educational level, were calculated. Differences in participation rates between those groups were compared. The diagnostic yield of both screening and nonscreening groups was calculated. RESULTS The study recruited 282 377 eligible participants and included 55 428 with high risk for lung cancer; the mean (SD) age was 55.3 (8.1) years, and 34 966 participants (63.1%) were men. A total of 22 260 participants underwent LDCT (participation rate, 40.16%; 95% CI, 39.82%-40.50%). The multivariable logistic regression model showed that female sex (odds ratio [OR], 1.64; 95% CI,

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Abstract: In an ongoing effort to identify molecular determinants regulating melanoma brain metastasis, we previously identified Angiopoietin-like 4 (ANGPTL4) as a component of the molecular signature of such metastases.The aim of this study was to determine the functional significance of ANGPTL4

Cited by 8 publications

References 45 publications

<p>The Metastasis Potential Promoting Capacity of Cancer-Associated Fibroblasts Was Attenuated by Cisplatin via Modulating KRT8</p>

<p>The Metastasis Potential Promoting Capacity of Cancer-Associated Fibroblasts Was Attenuated by Cisplatin via Modulating KRT8</p>

Neoadjuvant chemotherapy is associated with a transient increase of intratumoral T-cell density in microsatellite stable colorectal liver metastases

Evaluation of a Low-Dose Computed Tomography Lung Cancer Screening Program in Henan, China

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