Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. ...Tumor‐infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty‐four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post‐treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8+ TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8+ TILs in post‐treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8+ TILs in post‐treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte‐mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.
The antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy for rectal cancer. Our results showed that the density of CD8+ tumor‐infiltrating lymphocytes (TILs) in pretreatment biopsy samples of rectal cancer was positively correlated with the response to neoadjuvant chemoradiotherapy and chemotherapy. We concluded that the density of CD8+ TILs may be a predictor of the clinical effectiveness of neoadjuvant treatment.
The prognosis for patients with cancers known for a highly activated stromal reaction, including diffuse‐type (scirrhous) gastric cancer, consensus molecular subtype 4 (CMS4) colorectal cancer, and ...pancreatic ductal adenocarcinoma, is extremely poor. To explore the resistance of conventional therapy for those refractory cancers, detailed classification and investigation of the different subsets of cancer‐associated fibroblasts (CAFs) involved are needed. Recent studies with a single‐cell transcriptomics strategy (single‐cell RNA‐seq) have demonstrated that CAF subpopulations contain different origins and marker proteins with the capacity to either promote or suppress cancer progression. Through multiple signaling pathways, CAFs can promote tumor growth, metastasis, and angiogenesis with extracellular matrix (ECM) remodeling; they can also interact with tumor‐infiltrating immune cells and modulate the antitumor immunological state in the tumor microenvironment (TME). Here, we review the recent literature on the various subpopulations of CAFs to improve our understanding of the cell‐cell interactions in the TME and highlight future avenues for CAF‐targeted therapy.
The increasing prevalence of delayed and missed diagnoses for dementia constitutes major public concern. In this regard, inadequate knowledge and poor understanding of the condition may create a ...barrier to timely dementia screening. This cross-sectional study assessed dementia literacy, then identified the association between dementia literacy and willingness to undergo routine dementia screening among community-dwelling older adults in two urban areas of Japan. More specifically, structured questionnaires were distributed to a total of 854 individuals aged ≥ 65 years. A multivariate logistic regression was then used to explore the factors associated with dementia literacy and willingness to undergo routine dementia screening. Results showed that younger respondents and respondents who received dementia information from television/radio and/or paper-based sources were more likely to have high dementia literacy. While less than half of participants were willing to undergo routine dementia screening, those with higher dementia literacy were more willing to do so (albeit, not a statistically significant difference). Although there are pros and cons to routine dementia screening, it is necessary to implement such a system to detect dementia and cognitive impairment. Further, assessments should also attempt to gain information about individual beliefs and understandings related to dementia information.
To improve the quality of care for people with dementia, several local governments in Japan have implemented a subsidized system for screening of dementia. This cross‐sectional study aimed to ...identify factors that promote public intention to undergo dementia screening. A postal survey was conducted in a residential area that lies across the two cities which started a subsidized system for dementia screening. Semi‐structured questionnaires were distributed to community‐dwelling people aged ≥65 years; a total of 2269 persons were included in the analysis. χ2 test and multiple logistic regression analysis were used to identify factors associated with the willingness to undergo dementia screening. Among the people with dementia, only 28% had undergone a screening test for dementia. The participants who were certified of public long‐term care need tended to undergo dementia screening. Approximately 67% of the participants were willing to undergo a dementia diagnosis test. Younger age, female sex, perceived poor health status, having a primary care physician, and independent daily activity level were associated with a greater willingness to undergo dementia screening using a subsidized system. Our study showed that majority of people with possible dementia do not undergo dementia screening. However, majority of people were willing to use a subsidized system for dementia screening. Further studies are required to support the benefits of a subsidized dementia screening in primary care settings. J Am Geriatr Soc 68:‐, 2020.
Recently, the preoperative immune-nutritional status has been reported to correlate with the survival rate in patients with colorectal cancer (CRC). However, there have been no reports on the ...relationship between the controlling nutritional status (CONUT) score and the clinical outcome after curative surgery for CRC. We herein evaluated the prognostic significance of the CONUT score in patients with CRC, and then compared the accuracy of the CONUT score and the prognostic nutritional index (PNI) as a predictor of survival.
We retrospectively reviewed a database of 204 patients who underwent curative surgery for Stage II/III CRC. Patients were divided into two groups according to the CONUT score and the PNI.
The five-year cancer-specific survival (CSS) rate was significantly higher at 92.7% in the low CONUT group, compared to a rate of 81.0% in the high CONUT group (p=0.0016). The five-year CSS was 71.2% in the low PNI group and 92.3% in the high PNI group, which showed a significant difference (p=0.0155). A multivariate analysis showed that lymph node metastasis and the CONUT score were independent risk factors for CSS.
This study suggested that the CONUT score is a strong independent predictor of the survival among CRC patients.
Background
Although the role of Lipocalin-2 (LCN2) in cancer development has been focused on recent studies, the molecular mechanisms and clinical relevance of LCN2 in gastric cancer (GC) still ...remain unclear.
Methods
Transcriptome analysis of GC samples from public human data was performed according to Lauren’s classification and molecular classification. In vitro, Western blotting, RT-PCR, wound healing assay and invasion assay were performed to reveal the function and mechanisms of LCN2 in cell proliferation, migration and invasion using LCN2 knockdown cells. Gene set enrichment analysis (GSEA) of GC samples from public human data was analyzed according to LCN2 expression. The clinical significance of LCN2 expression was investigated in GC patients from public data and our hospital.
Results
LCN2 was downregulated in diffuse-type GC, as well as in Epithelial–Mesenchymal Transition (EMT) type GC. LCN2 downregulation significantly promoted proliferation, invasion and migration of GC cells. The molecular mechanisms of LCN2 downregulation contribute to Matrix Metalloproteinases-2 (MMP2) stimulation which enhances EMT signaling in GC cells. GSEA revealed that LCN2 downregulation in human samples was involved in EMT signaling. Low LCN2 protein and mRNA levels were significantly associated with poor prognosis in patients with GC. LCN2 mRNA level was an independent prognostic factor for overall survival in GC patients.
Conclusions
LCN2 has a critical role in EMT signaling via MMP2 activity during GC progression. Thus, LCN2 might be a promising therapeutic target to revert EMT signaling in GC patients with poor outcomes.
Inflammation is widely recognized to play an important role in cancer progression, and the peripheral monocyte count has been reported to correlate with the prognosis in patients with colorectal ...cancer. This is based on the hypothesis that the peripheral monocyte level and the density of tumor-associated macrophages (TAMs) in the cancer microenvironment correlate with each other. However, the influence of TAMs on the prognosis and the correlation between the peripheral monocyte count and the density of TAMs have not yet been elucidated.
A total of 168 patients with stage II/III colorectal cancer were enrolled in this study. Preoperative blood samples were obtained at the time of the diagnosis before surgery. The expression of TAMs in the cancer microenvironment was assessed by immunohistochemistry.
The progression-free and overall survival rate were significantly worse in the high-TAMs group than in the low-TAMs group (p = 0.0012 and p = 0.0207, respectively). The peripheral monocyte count was significantly associated with the number of TAMs (correlation coefficients: 0.202, p = 0.047).
The peripheral monocyte count was associated with the density of the TAMs, which created a microenvironment favorable for cancer development and were correlated with a poor prognosis. Therefore, the peripheral monocyte count is a useful prognostic marker reflecting the status of the tumor microenvironment.
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