The epithelial–mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular ...mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2009)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
When conducting experimental psychology, psychological phenomena are often described in mathematical terms and logic. How practical is the mathematical approach in experimental psychology? This paper ...aims to explain plain linguistic and mathematical expressions, how psychological phenomena are expressed mathematically in experimental psychology and how mathematical models are constructed, using examples of psychological phenomena related to sensation, perception, and cognition. First, it outlined the perspective, thinking, and utilization of mathematical models in experimental psychology, using some psychological phenomena. Second, it was introduced that several previous studies dealt with spatial properties of perceptual and cognitive phenomena, including the author’s studies. It is hoped that this paper will increase familiarity with and opportunities to utilize mathematical models in experimental psychology.
Malnutrition has been considered to be associated with the prognosis of cancer. The Geriatric Nutritional Risk Index (GNRI), based on serum albumin levels, present body weight, and ideal body weight, ...is a simple screening tool to predict the risk of nutrition-related morbidity and mortality in elderly patients. We aimed to evaluate whether preoperative GNRI was associated with postoperative complications and prognosis in elderly patients with colorectal cancer (CRC). We retrospectively enrolled 313 CRC patients aged ≥65 years after curative surgery and classified them into an all-risk GNRI (≤98) group and a no-risk GNRI (>98) group. Kaplan-Meier analysis showed overall survival was significantly worse in the all-risk GNRI group than in the no-risk GNRI group (P = 0.009). Multivariable analyses showed low GNRI (≤98) was an independent risk factor for postoperative complications (P = 0.048) and overall survival (P = 0.001) in the patients. Among the complications, the incidence of surgical site infection, in particular, was significantly higher in the all-risk GNRI group (P = 0.008). In conclusion, low preoperative GNRI (≤98) was associated with increased postoperative complications and poor prognosis. Preoperative GNRI can be used as an identifier for potential high-risk group of morbidity and mortality in elderly CRC patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival in patients with resected colorectal cancer. Potential utility of circulating tumor DNA (ctDNA) prior to and post ...surgery has been reported across various solid tumors. We initiated a new type of adaptive platform trials to evaluate the clinical benefits of ctDNA analysis and refine precision adjuvant therapy for resectable colorectal cancer, named CIRCULATE‐Japan including three clinical trials. The GALAXY study is a prospectively conducted large‐scale registry designed to monitor ctDNA for patients with clinical stage II to IV or recurrent colorectal cancer who can undergo complete surgical resection. The VEGA trial is a randomized phase III study designed to test whether postoperative surgery alone is noninferior to the standard therapy with capecitabine plus oxaliplatin for 3 months in patients with high‐risk stage II or low‐risk stage III colon cancer if ctDNA status is negative at week 4 after curative surgery in the GALAXY study. The ALTAIR trial is a double‐blind, phase III study designed to establish the superiority of trifluridine/tipiracil as compared with placebo in patients with resected colorectal cancer who show circulating tumor–positive status in the GALAXY study. Therefore, CIRCULATE‐Japan encompasses both “de‐escalation” and “escalation” trials for ctDNA‐negative and ‐positive patients, respectively, and helps to answer whether measuring ctDNA postoperatively has prognostic and/or predictive value. Our ctDNA‐guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy. Analysis of ctDNA status could be utilized as a predictor of risk stratification for recurrence and to monitor the effectiveness of adjuvant chemotherapy. ctDNA is a promising, noninvasive tumor biomarker that can aid in tumor monitoring throughout disease management.
CIRCULATE‐Japan encompasses both “de‐escalation” and “escalation” trials for circulating tumor DNA–negative and –positive patients, respectively, and helps to answer whether measuring circulating tumor DNA postoperatively has prognostic and/or predictive value. Our circulating tumor DNA–guided adaptive platform trials will accelerate clinical development toward further precision oncology in the field of adjuvant therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
WRKY62 is a transcriptional repressor regulated downstream of WRKY45, a central transcription factor of the salicylic acid signaling pathway in rice. Previously, WRKY62 was reported to regulate ...defense negatively. However, our expressional analysis using WRKY62-knockdown rice indicated that WRKY62 positively regulates defense genes, including diterpenoid phytoalexin biosynthetic genes and their transcriptional regulator DPF. Blast and leaf blight resistance tests also showed that WRKY62 is a positive defense regulator. Yeast two-hybrid, co-immunoprecipitation and gel-shift assays showed that WRKY45 and WRKY62 can form a heterodimer, as well as homodimers, that bind to W-boxes in the DPF promoter. In transient assays in rice sheaths, the simultaneous introduction of WRKY45 and WRKY62 as effectors resulted in a strong activation of the DPF promoter:hrLUC reporter gene, whereas the activity declined with excessive WRKY62. Thus, the WRKY45-WRKY62 heterodimer acts as a strong activator, while the WRKY62 homodimer acts as a repressor. While benzothiadiazole induced equivalent numbers of WRKY45 and WRKY62 transcripts, consistent with heterodimer formation and DPF activation, submergence and nitrogen replacement induced only WRKY62 transcripts, consistent with WRKY62 homodimer formation and DPF repression. Moreover, WRKY62 positively regulated hypoxia genes, implying a role forWRKY62 in the modulation of the 'trade-off' between defense and hypoxia responses.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
N6-methyladenosine (m6A) is the most abundant epitranscriptome modification in mammalian mRNA. Recent years have seen substantial progress in m6A epitranscriptomics, indicating its crucial roles in ...the initiation and progression of cancer through regulation of RNA stabilities, mRNA splicing, microRNA processing and mRNA translation. However, by what means m6A is dynamically regulated or written by enzymatic components represented by methyltransferase-like 3 (METTL3) and how m6A is significant for each of the numerous genes remain unclear. We focused on METTL3 in pancreatic cancer, the prognosis of which is not satisfactory despite the development of multidisciplinary therapies. We established METTL3-knockdown pancreatic cancer cell line using short hairpin RNA. Although morphologic and proliferative changes were unaffected, METTL3-depleted cells showed higher sensitivity to anticancer reagents such as gemcitabine, 5-fluorouracil, cisplatin and irradiation. Our data suggest that METTL3 is a potent target for enhancing therapeutic efficacy in patients with pancreatic cancer. In addition, we performed cDNA expression analysis followed by Gene Ontology and protein-protein interaction analysis using the Database for Annotation, Visualization, and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes/Proteins databases, respectively. The results demonstrate that METTL3 was associated with mitogen-activated protein kinase cascades, ubiquitin-dependent process and RNA splicing and regulation of cellular process, suggesting functional roles and targets of METTL3.
Background
The morbidity rate after pancreaticoduodenectomy remains high. The objectives of this retrospective cohort study were to clarify the risk factors associated with serious morbidity ...(Clavien–Dindo classification grades IV–V), and create complication risk calculators using the Japanese National Clinical Database.
Methods
Between 2011 and 2012, data from 17,564 patients who underwent pancreaticoduodenectomy at 1,311 institutions in Japan were recorded in this database. The morbidity rate and associated risk factors were analyzed.
Results
The overall and serious morbidity rates were 41.6% and 4.5%, respectively. A pancreatic fistula (PF) with an International Study Group of Pancreatic Fistula (ISGPF) grade C was significantly associated with serious morbidity (P < 0.001). Twenty‐one variables were considered statistically significant predictors of serious complications, and 15 of them overlapped with those of a PF with ISGPF grade C. The predictors included age, sex, obesity, functional status, smoking status, the presence of a comorbidity, non‐pancreatic cancer, combined vascular resection, and several abnormal laboratory results. C‐indices of the risk models for serious morbidity and grade C PF were 0.708 and 0.700, respectively.
Conclusions
Preventing a PF grade C is important for decreasing the serious morbidity rate and these risk calculations contribute to adequate patient selection.
HighlightAoki and colleagues clarified the risk factors associated with serious morbidity (Clavien‐Dindo classification grades IV–V) and created risk calculators using a Japanese nationwide database of 17,564 patients after pancreaticoduodenectomy. Preventing pancreatic fistula grade C is important for reducing serious morbidity and these risk calculations contribute to more appropriate patient selection.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Systemic inflammation has been correlated with worse survival for some cancers. We evaluated prognostic values of various inflammatory factor combinations in patients who underwent ...resections for hepatocellular carcinoma (HCC).
Methods
We retrospectively analysed 306 consecutive patients with HCC who underwent curative liver resections. After assessing eight combinations of inflammatory markers for predictive value for recurrence, we focused on lymphocyte-to-C-reactive protein ratio (LCR) to elucidate its associations with recurrence-free survival (RFS) and overall survival (OS) in univariate and multivariate analyses (Cox proportional hazards model). We also used immunohistochemical CD34 and CD8 staining to investigate the mechanism of LCR elevation.
Results
LCR showed the highest association with RFS in HCC patients among the compared indices. High preoperative LCR correlated with a high serum albumin concentration, small tumour size, early Barcelona Clinic Liver Cancer stage and low rates of microscopic vascular invasion and microscopic intrahepatic metastasis. Higher preoperative LCR was an independent predictor of longer RFS and OS in this cohort. High LCR patients had fewer vessels encapsulating tumour clusters, and higher intratumoural CD8
+
T-cell counts than low LCR patients.
Conclusions
Preoperative LCR is a novel and convenient prognostic marker for patients with HCC, and is associated with the tumour microenvironment immune status.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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