Debate exists as to whether CRTC1/3‐MAML2 fusions have a prognostic significance in salivary mucoepidermoid carcinoma (MEC). We undertook a multiinstitutional study including 153 MEC cases, and found that the fusions were an excellent biomarker for better overall survival in the total and advanced‐stage MEC cohorts. Abstract Mucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3‐MAML2 fusions are...
Mon Sep 14, 2020 21:23
Lysosome‐associated membrane protein type 2a (LAMP2A) is the key receptor protein of chaperone‐mediated autophagy (CMA). Downregulation of LAMP2A leads to CMA blockade. Our discoveries suggest that LAMP2A is involved in the regulation of cancer malignant phenotypes through CMA modulation and represents a promising new target against chemoresistant non–small cell lung cancer (NSCLC). Abstract Chaperone‐mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins....
Mon Sep 07, 2020 13:54
In this study, we examined the functions of suppressor of Ty 16 (Spt16) in lung cancer cells. We showed that Spt16 is upregulated in lung cancers and is correlated with the poor prognosis of lung cancer patients. Knockdown of Spt16 in lung cancer cells inhibited the proliferation and metastasis of lung cancer cells both in vitro and in vivo. We also determined a novel mechanism for the regulation of Spt16 expression by miRNA‐1227‐5p. Abstract Suppressor of Ty 16 (Spt16) is a component of the...
Thu Sep 17, 2020 17:56
This study provides direct experimental evidence for case‐control studies reporting an association between the presence of low‐function UGT1A variants and an increased tumor incidence which can be protectively modified by coffee consumption. Abstract UDP‐glucuronosyltransferase (UGT) 1A enzymes detoxify a broad array of exogenous compounds including environmental toxins and carcinogens. Case‐control studies identified genetic variations in UGT1A genes leading to reduced glucuronidation activity,...
Sat Sep 05, 2020 22:00
Cell line experiments showed a potential RP11‐1094M14.8/miR‐1269a/CXCL9 axis that was consistent with the ceRNA theory. The RP11‐1094M14.8/miR‐1269a/CXCL9 axis may serve as a potential immune‐therapeutic target for gastric cancer with different degrees of immune cell infiltration Abstract Immune cell infiltration is an important indicator of whether tumor patients will benefit from immunotherapy. Gastric cancer is one of the most common tumors in the world, and new indicators of immunotherapy...
Fri Sep 11, 2020 21:35
We revealed that 2 major histopathological types of renal cell carcinomas (RCCs) that arise in end‐stage renal disease (ESRD), namely clear‐cell RCCs (ESRD‐ccRCCs) and acquired cystic disease (ACD)‐associated RCCs, had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively. This finding indicates that these 2 histopathological types of RCCs arising in ESRD originated from proximal tubule cells of a nephron. Abstract End‐stage renal disease (ESRD)...
Fri Sep 18, 2020 18:15
Abstract Copy number variation (CNV) is a polymorphism in the human genome involving DNA fragments larger than 1kb. CNV sites provide hotspots of somatic alterations in cancers. Herein, we examined somatic alterations at sites of CNV in DNA from 20 invasive breast cancers using a Comparative Genomic Hybridization array specifically designed to detect the genome‐wide CNV status of around 412,000 sites. Somatic copy number alterations (CNAs) were detected in 39.9% of the CNV probes examined. The most...
Sat Aug 29, 2020 11:36
Abstract Accumulating evidence has identified long noncoding RNAs (lncRNAs) as regulators in tumor progression and development. Here, we elucidated the function and possible molecular mechanisms of the effect of lncRNA‐PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA) on the biological behaviors of HCC. In the present study, we found that PICSAR was upregulated in HCC tissues and cells and correlated with progression and poor prognosis in HCC patients. Gain‐ and loss‐of‐function...
Wed Sep 23, 2020 15:46
Neoadjuvant radiotherapy could not increase survival for baseline low‐risk (cT3, cN0, cII stage) subgroup locally advanced rectal cancer patients. But neoadjuvant radiotherapy should not be removed from neoadjuvant treatment regimen for the baseline high‐risk (cT4, cN+, cIII) subset locally advanced rectal cancer patients. Abstract Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision and adjuvant chemotherapy is the standard regimen for patients with locally advanced rectal...
Tue Sep 15, 2020 12:50
The present study suggests that Girdin overexpression perturbs cell cycle distribution with prolonged G1 and M phases and aberrant p53 activation, which leads to an increase in sensitivity to DNA damage. It also showed that the upregulation of the spindle checkpoint protein Mad2 in Girdin‐overexpressing cells could be involved in dysregulated cell cycle progression. Abstract The actin‐binding protein Girdin is a hub protein that interacts with multiple proteins to regulate motility and Akt...
Sat Sep 19, 2020 15:24
Our results might indicate that no IL‐10/STAT‐3/PD‐L1 pathways were involved in the synergistic effect. Then some other mechanism in the microenvironment might be a possible target for ibrutinib. We expect our results would provide evidence for the use of ibrutinib in polytherapy for other types of B‐cell lymphoma. Abstract Ibrutinib might improve the efficacy of anti‐CD19 chimeric antigen receptor (CD19 CAR) T‐cell therapy in chronic lymphocytic leukemia (CLL). We studied the possibility and...
Tue Sep 15, 2020 12:33
Direct delivery of an anticancer drugs into the lymphatic system using a novel lymphatic drug delivery system (LDDS) was an effective treatment for early‐stage lymph node (LN) metastasis in a mouse model. Intranodal pressure (INP) reflects tumor activity in tumor‐bearing LN. Therefore, measurement of INP could be a useful method to evaluate the therapeutic effects of cancer treatment given using an LDDS. Abstract Cancer metastasis to lymph nodes (LNs) almost certainly contributes to distant...
Fri Sep 18, 2020 21:18
The expression of recombination signal binding protein for immunoglobulin kappa J region (RBPJ) tended to correlate positively with malignancy of glioma and is highly expressed in glioblastoma stem‐like cells (GSCs). RBPJ in GSCs may relate to not only tumor progression and stemness maintenance through the IL‐6‐STAT3 pathway but also proneural‐mesenchymal transition initiating phenotype shift. RBPJ may be a novel therapeutic target for GSCs. Abstract Notch signaling plays a pivotal role in...
Tue Sep 22, 2020 11:38
Cover of this issue. An image of extracellular vesicles isolated from 22Rv1 cells under transmission electron microscopy. See also Urabe et al. (pp. https://doi.org/10.1111/cas.145353258‐3267 of this issue).
Thu Sep 03, 2020 22:00
In 1955, an outbreak of arsenic poisoning caused by the ingestion of arsenic‐contaminated Morinaga Dry Milk occurred in western Japan. This study aimed to assess the mortality and cancer incidence risk among Japanese individuals who were poisoned during this time as infants. Abstract In 1955, an outbreak of arsenic poisoning caused by the ingestion of arsenic‐contaminated Morinaga Dry Milk occurred in western Japan. This study aimed to assess the mortality and cancer incidence risk among Japanese...
Sat Sep 05, 2020 12:34
Cancer stem cells (CSCs) are a rational target for curable cancer treatment, but the development of effective CSC‐targeted therapies is moving at a restricted pace. This review article summarizes the recent advances in the understanding of the mechanism of tumor‐promoting interactions between CSCs and their niche tumor microenvironment. Abstract Most cancers harbor a small population of highly tumorigenic cells known as cancer stem cells (CSCs). Because of their stem cell‐like properties and...
Fri Sep 18, 2020 21:30
Abstract Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Cancer Genome Atlas database analysis and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. URB1 silencing hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment...
Sat Sep 05, 2020 13:08
Advanced hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) is often associated with chronic inflammation, liver injury, immune tolerance, and poor clinical outcomes. Due to drug toxicity and side‐effects, current targeted drugs including sorafenib are unfortunately not favorable treatment options, particularly for those advanced HCC patients with poor prognosis. Herbal‐derived natural small molecule icaritin showed anticancer immunomodulatory efficacy with superior safety and improved...
Thu Sep 24, 2020 20:20
Circulating circERBB2 as a potential prognostic biomarker for gastric cancer: An investigative study
In patients with gastric cancer, high levels of preoperative plasma circERBB2 showed poor prognosis and the plasma level of circERBB2 increased at recurrence. Plasma circERBB2 can be a noninvasive prognostic biomarker and useful for the detection of gastric cancer recurrences. Abstract Circular RNA is a novel endogenous non‐coding RNA that can serve as a biomarker because of its stable loop structure. We investigated and examined the utility of plasma circERBB2 as a prognostic biomarker in...
Sat Sep 19, 2020 20:05
ABSTRACT Epigenetic gene silencing by aberrant DNA methylation is one of the important mechanisms leading to loss of key cellular pathways in tumorigenesis. Methyl‐CpG targeted transcriptional activation (MeTA) reactivates hypermethylation‐mediated silenced genes in a different way from DNA demethylating agents. Microarray coupled with MeTA (MeTA‐array) identified seven commonly hypermethylation‐mediated silenced genes in 12 pancreatic ductal adenocarcinoma (PDAC) cell lines. Among these, we focused...
Mon Sep 07, 2020 22:09
Summary Various clinical and experimental findings have revealed the causal relationship between autophagy failure and oncogenesis, and several mechanisms have been suggested to explain this relationship. We recently proposed two additional mechanisms: centrosome number dysregulation and the failure of autophagic cell death. Here, we detail the mechanical relationship between autophagy failure and oncogenesis.
Tue Sep 08, 2020 18:37
Abstract Cervical cancer (CC) remains one of the leading causes of mortality of female cancers worldwide, with more than 90% of them are cervical squamous cell carcinoma (CSCC). ΔNp63α is the predominant isoform expressed in cervical epithelial tissues and exerts its anti‐tumor function in CSCC. In this study, we have identified 39 long noncoding RNAs as ΔNp63α targets in CSCC through RNA‐sequencing and chromatin immunoprecipitation‐sequencing, in which we further confirmed and focused on the two...
Sat Sep 12, 2020 17:59
Abstract This prespecified subanalysis of the global, randomized controlled phase 3 KEYNOTE‐024 study of pembrolizumab versus chemotherapy in previously untreated metastatic non–small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score ≥50% evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (4‒6 cycles). The primary endpoint was progression‐free survival; secondary...
Mon Sep 14, 2020 12:39
Abstract Abnormal activation of Nuclear factor kappa B (NF‐κB) signaling pathway is closely implicated in triple‐negative breast cancer (TNBC) growth, metastasis and tumor immune escape. In this study, the anti‐cancer effects of icariin, a natural flavonol glycoside, towards breast cancer cells and the underlying mechanisms were investigated. This investigation showed that icariin selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration‐ and time‐dependent...
Mon Sep 14, 2020 14:04
Summary To compare the effectiveness of carbon‐ion radiation therapy (CIRT), proton radiation therapy (PRT) and photon‐based intensity‐modulated radiation therapy (IMRT) in the treatment of sinonasal malignancies. We identified studies through systematic review and divided into three cohorts (CIRT group/PRT group/IMRT group). Primary outcomes of interest were overall survival (OS) and local control (LC). We pooled the outcomes with meta‐analysis and compared the survival difference among groups...
Wed Sep 16, 2020 21:01
Abstract Some cancers are related to atherosclerotic diseases, therefore these two types of disease may share some antibody biomarkers in common. To investigate this, a first screening was performed of sera from patients with esophageal squamous cell carcinoma (ESCC) or acute ischemic stroke (AIS) for serological identification of antigens using recombinant cDNA expression cloning (SEREX). The amplified luminescent proximity homogeneous assay‐linked immunosorbent assay (AlphaLISA) method, which...
Wed Sep 16, 2020 20:44
Summary The efficacy of azacitidine (AZA) on survival of lower risk (LR) ‐ myelodysplastic syndromes (MDS) is controversial. To address this issue, we retrospectively evaluated the long‐term survival benefit of AZA for patients with LR‐MDS defined by International Prognostic Scoring System (IPSS). Using data from 489 patients with LR‐MDS in Nagasaki, hematologic responses according to International Working Group 2006 and overall survival (OS) were compared among patients that received best supportive...
Thu Sep 17, 2020 11:39
Abstract Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of hepatocellular carcinoma (HCC), but the underlying mechanisms behind the correlation of non‐alcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) are unclear. We aim to uncover the genes and potential mechanisms that drive the progression. This study uncovered the genes and potential mechanisms through a multiple‐omics integration approach. The quantitative proteomics combined with phenotype‐association...
Thu Sep 17, 2020 18:29
Abstract Fibroblast growth factor receptor (FGFR) is associated with proliferation, migration, and angiogenesis of carcinomas, and FGFR signaling inhibitors are considered a key drug for the treatment of solid tumors with FGFR overexpression. Amplification of FGFR2 is reportedly identified in 3‐10% of gastric cancer (GC). The aim of this study is to clarify whether the identification of the circulating tumor cells (CTCs) with FGFR2 overexpression is useful to detect patients with FGFR2 overexpress...
Fri Sep 18, 2020 22:44
Abstract In the global phase III RELAY study, ramucirumab plus erlotinib (RAM+ERL) demonstrated superior progression‐free survival (PFS) to placebo plus erlotinib (PL+ERL) in untreated patients with EGFR mutation–positive metastatic NSCLC (HR [95% CI]: 0.59 [0.46‐0.76]). This prespecified analysis assessed RAM+ERL efficacy and safety in the RELAY subset enrolled in East Asia (Japan, Taiwan, South Korea, Hong Kong). Randomized (1:1) patients received oral ERL (150 mg/day) plus intravenous RAM (10...
Sun Sep 20, 2020 18:35
Abstract Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production...
Thu Sep 24, 2020 13:28
Abstract Our laboratory previously reported the usefulness of exosomes in the plasma of esophageal squamous cell carcinoma (ESCC) patients as a biomarker. However, the influence of tumor‐derived exosomes on the tumor itself and underlying mechanisms remain unclear. We herein report the changes in the phenotype and gene expression when cancer cells exist in an environment with tumor‐derived exosomes. The exosomes were isolated from the culture medium of human ESCC cells (TE2, T.Tn) by ultracentrifugation,...
Thu Sep 24, 2020 13:30
Abstract Protein Phosphatase 6 (PP6) is an essential serine/threonine protein phosphatase that acts as an important tumor suppressor. However, increased protein levels of PP6 have been observed in some cancer types, and correlate with poor prognosis in glioblastoma. This raises a question about how PP6 protein levels are regulated in normal and transformed cells. In this study, we show that PP6 protein levels increase in response to pharmacologic and genetic inhibition of autophagy. PP6 associates...
Thu Sep 24, 2020 13:32
Abstract Diagnostic markers for both colorectal cancer (CRC) and its precursor lesions are lacking. Although aberrant methylation of SCTR gene was observed in CRC, the diagnostic performance has not been evaluated. Therefore, this study aimed to assess and verify the diagnostic value of SCTR methylation of CRC and its precursor lesions through integrating the largest methylation data. The diagnostic performance of SCTR methylation was analyzed in the discovery set from The Cancer Genome Atlas (TCGA)...
Thu Sep 24, 2020 16:44
Abstract Isatuximab, an anti‐CD38 monoclonal antibody, targets cells that strongly express CD38 including malignant plasma cells. This open‐label, single‐arm, multicenter Phase 1/2 trial investigated the tolerability/safety and efficacy of isatuximab monotherapy in Japanese patients with heavily pretreated, relapsed/refractory multiple myeloma (RRMM). In Phase 1, patients were sequentially assigned to receive isatuximab once weekly (QW) in cycle 1 (4 weeks) and every 2 weeks (Q2W) in subsequent...
Fri Sep 25, 2020 17:09
ABSTRACT We aimed to examine whether the number of types of hazardous operations at work experienced through a lifetime is associated with cancer incidence, and additionally examined the combined effects with lifestyle‐related factors. Using a nationwide, multicenter, hospital inpatient dataset (2005‐2015), we conducted a matched case‐control study with 1,149,296 study subjects. We classified the participants into those with none, one, and two or more types of hazardous operation experience, based...
Fri Sep 25, 2020 17:11
Abstract Adult T‐cell leukemia/lymphoma (ATL) is a mature T‐cell neoplasm and is classified into four subtypes (acute, lymphoma, chronic, and smoldering) according to the Shimoyama classification, established in 1991 through several nationwide surveys based on the clinical diversity of patients diagnosed in 1983–1987 in Japan. Thereafter, no such studies have been conducted. Recently, we conducted a nationwide hospital survey using the method of the 1980s studies, collected baseline data on 996...
Fri Sep 25, 2020 21:20
Abstract Metastatic progression remains the major cause of death in human breast cancer. Cancer cells with cancer stem cell (CSC) properties drive initiation and growth of metastases at distant sites. We have previously established the breast cancer patient‐derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, the expression levels of S100A10 and its family proteins were much higher in the CD44+...
Fri Sep 25, 2020 21:30
Abstract Cellular migration, coupled with the degradation of the extracellular matrix (ECM), is a key step in tumor invasion and represents a promising therapeutic target in malignant tumors. Focal adhesions (FAs) and invadopodia, which are distinct actin‐based cellular structures, play key roles in cellular migration and ECM degradation, respectively. The molecular machinery coordinating the dynamics between FAs and invadopodia is not fully understood, although several lines of evidence suggest...
Fri Sep 25, 2020 21:46
Abstract Chemical carcinogenesis is focused on the formation of DNA adducts, a form of DNA damage caused by covalent binding of a chemical moiety to DNA. The detection of carcinogen‐DNA adducts in human tissues, along with demonstration of mutagenicity/carcinogenicity in experimental systems, and validation of adducts as biomarkers of environmental exposure and indicators of cancer risk in molecular epidemiological studies suggests pivotal role of DNA adducts in cancer development. However, accurate...
Sat Sep 26, 2020 11:51
Abstract Interaction of cancer cells with cancer‐associated fibroblasts (CAFs) play critical roles in tumor progression. Recently we proposed a new tumor invasion mechanism in which invasive cancer cells individually migrate on elongate protrusions of CAFs (CAF fibers) in three‐dimensional collagen matrix. In this mechanism, cancer cells interact with fibronectin fibrils assembled on CAFs mainly through integrin α5β1. Here we tested whether this mechanism is applicable to the collective invasion...
Sat Sep 26, 2020 13:10
Abstract Causal inference is one of the challenges in epidemiologic studies. Gynecologic diseases have been reported to have association with obesity, however, the causality remained controversial except for uterine endometrial cancer. We conducted two‐sample Mendelian randomization (MR) analysis using the large‐scale genome‐wide association study (GWAS) results of gynecologic diseases and body mass index (BMI) in Japanese population to assess causal effect of BMI on gynecologic diseases. We first...
Sun Sep 27, 2020 15:24
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