Publications by authors named "Yusuke Yamamoto"

367 Publications

Selective targeting of KRAS-driven lung tumorigenesis via unresolved ER stress.

JCI Insight 2021 Apr 8;6(7). Epub 2021 Apr 8.

Division of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.

Lung cancer with oncogenic KRAS makes up a significant proportion of lung cancers and is accompanied by a poor prognosis. Recent advances in understanding the molecular pathogenesis of lung cancer with oncogenic KRAS have enabled the development of drugs, yet mutated KRAS remains undruggable. We performed small-molecule library screening and identified verteporfin, a yes-associated protein 1 (YAP1) inhibitor; verteporfin treatment markedly reduced cell viability in KRAS-mutant lung cancer cells in vitro and suppressed KRAS-driven lung tumorigenesis in vivo. Comparative functional analysis of verteporfin treatment and YAP1 knockdown with siRNA revealed that the cytotoxic effect of verteporfin was at least partially independent of YAP1 inhibition. A whole-transcriptome approach revealed the distinct expression profiles in KRAS-mutant lung cancer cells between verteporfin treatment and YAP1 knockdown and identified the selective involvement of the ER stress pathway in the effects of verteporfin treatment in KRAS-mutant lung cancer, leading to apoptotic cell death. These data provide novel insight to uncover vulnerabilities in KRAS-driven lung tumorigenesis.
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http://dx.doi.org/10.1172/jci.insight.137876DOI Listing
April 2021

Breast Cancer Brain Metastasis-Overview of Disease State, Treatment Options and Future Perspectives.

Cancers (Basel) 2021 Mar 3;13(5). Epub 2021 Mar 3.

Department of Breast Surgery, National Cancer Center Hospital, Tokyo 104-0045, Japan.

Breast cancer is the second most common origin of brain metastasis after lung cancer. Brain metastasis in breast cancer is commonly found in patients with advanced course disease and has a poor prognosis because the blood-brain barrier is thought to be a major obstacle to the delivery of many drugs in the central nervous system. Therefore, local treatments including surgery, stereotactic radiation therapy, and whole-brain radiation therapy are currently considered the gold standard treatments. Meanwhile, new targeted therapies based on subtype have recently been developed. Some drugs can exceed the blood-brain barrier and enter the central nervous system. New technology for early detection and personalized medicine for metastasis are warranted. In this review, we summarize the historical overview of treatment with a focus on local treatment, the latest drug treatment strategies, and future perspectives using novel therapeutic agents for breast cancer patients with brain metastasis, including ongoing clinical trials.
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http://dx.doi.org/10.3390/cancers13051078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959316PMC
March 2021

ChrXq27.3 miRNA cluster functions in cancer development.

J Exp Clin Cancer Res 2021 Mar 25;40(1):112. Epub 2021 Mar 25.

Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Tsuruma-cho 65, Showa-ku, Nagoya, 466-8550, Japan.

MicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer.The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial-mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888-892 group are considered to be cell type- or tissue-specific.In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets.
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http://dx.doi.org/10.1186/s13046-021-01910-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992321PMC
March 2021

Ygr125w/Vsb1-dependent accumulation of basic amino acids into vacuoles of Saccharomyces cerevisiae.

Biosci Biotechnol Biochem 2021 Jan 28. Epub 2021 Jan 28.

Laboratory of Molecular Physiology and Genetics, Graduate School of Agriculture, Ehime University, Matsuyama, Japan.

The Ygr125w was previously identified as a vacuolar membrane protein by a proteomic analysis. We found that vacuolar levels of basic amino acids drastically decreased in ygr125wΔ cells. Since N- or C-terminally tagged Ygr125w was not functional, an expression plasmid of YGR125w with HA3-tag inserted in its N-terminal hydrophilic region was constructed. Introduction of this plasmid into ygr125w∆ cells restored the vacuolar levels of basic amino acids. We successfully detected the uptake activity of arginine by the vacuolar membrane vesicles depending on HA3-YGR125w expression. A conserved aspartate residue in the predicted first transmembrane helix (D223) was indispensable for the accumulation of basic amino acids. YGR125w has been recently reported as a gene involved in vacuolar storage of arginine; and it is designated as VSB1. Taken together, our findings indicate that Ygr125w/Vsb1 contributes to the uptake of arginine into vacuoles and vacuolar compartmentalization of basic amino acids.
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http://dx.doi.org/10.1093/bbb/zbab015DOI Listing
January 2021

Open Abdomen Negative Pressure Device Applied for Two-stage Closure of Enterocutaneous Fistula.

Plast Reconstr Surg Glob Open 2021 Feb 1;9(2):e3369. Epub 2021 Feb 1.

Department of Plastic Surgery, Shizuoka General Hospital, Shizuoka, Japan.

Enterocutaneous fistula (ECF), which is an abnormal connection between the gastrointestinal tract and skin, is a serious complication of abdominal surgery, and a multidisciplinary approach is required for its treatment. Here, we report the case of a 46-year-old woman who had a large ECF measuring 6 × 12 cm that was successfully treated with a 2-stage surgery. After the first surgery of intestinal wall reconstruction, an abdominal negative pressure wound therapy (NPWT) device was administered to facilitate the reexploration of the abdominal cavity. On postoperative day 5, intestinal perforation and abdominal cavity infection were found during dressing change and were immediately repaired. Subsequently, after 10 days of abdominal NPWT, the second surgery comprising abdominal wall reconstruction was performed using a pedicled anterolateral thigh flap (8 × 19 cm) combined with the fascia lata (12 × 20 cm). The defective rectus sheath and skin were uneventfully closed with the fascia lata and flap skin paddle, respectively. In the follow-up after 7 months, ECF had not recurred. The abdominal NPWT device enabled easy reentry of the abdominal cavity and reduced the size of the flap needed to cover the defect. Moreover, open abdominal management can be performed consistently, independent of the surgeon's expertise. Therefore, this report suggests that 2-stage surgery with abdominal NPWT management is a useful strategy for ECF treatment.
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http://dx.doi.org/10.1097/GOX.0000000000003369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929538PMC
February 2021

The In Vivo Selection Method in Breast Cancer Metastasis.

Int J Mol Sci 2021 Feb 14;22(4). Epub 2021 Feb 14.

Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan.

Metastasis is a complex event in cancer progression and causes most deaths from cancer. Repeated transplantation of metastatic cancer cells derived from transplanted murine organs can be used to select the population of highly metastatic cancer cells; this method is called as in vivo selection. The in vivo selection method and highly metastatic cancer cell lines have contributed to reveal the molecular mechanisms of cancer metastasis. Here, we present an overview of the methodology for the in vivo selection method. Recent comparative analysis of the transplantation methods for metastasis have revealed the divergence of metastasis gene signatures. Even cancer cells that metastasize to the same organ show various metastatic cascades and gene expression patterns by changing the transplantation method for the in vivo selection. These findings suggest that the selection of metastasis models for the study of metastasis gene signatures has the potential to influence research results. The study of novel gene signatures that are identified from novel highly metastatic cell lines and patient-derived xenografts (PDXs) will be helpful for understanding the novel mechanisms of metastasis.
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http://dx.doi.org/10.3390/ijms22041886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918415PMC
February 2021

Single-cell qPCR Assay with Massively Parallel Microfluidic System.

Bio Protoc 2020 Mar 20;10(6):e3563. Epub 2020 Mar 20.

Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.

The single-cell transcriptome is the set of messenger RNA molecules expressed in one cell. It is extremely variable and changes according to external, physical and biochemical conditions. Due to sensitivity shortages, most of genetic studies use bulk samples, providing only the average gene expression. Single-cell technologies have provided a powerful approach to a more detailed understanding of the heterogenic populations and minority cells. However, since it is still a quite novel technique, standardized protocol has to be established. Single-cell qPCR, although partly limited by the number of genes, is relatively simple to analyze. Therefore, its use is accessible without the necessity to recourse to complex bioinformatics analyses. The main steps for single-cell qPCR, as illustrated in this protocol, are composed by single-cell isolation, cell lysate, cDNA reverse-transcription synthesis, amplification for cDNA library generation, and finally, quantitative polymerase chain reaction.
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http://dx.doi.org/10.21769/BioProtoc.3563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842821PMC
March 2020

Amino acid derivative reactivity assay-organic solvent reaction system: A novel alternative test for skin sensitization capable of assessing highly hydrophobic substances.

J Appl Toxicol 2021 Feb 26. Epub 2021 Feb 26.

Safety Science Research Laboratories, Lion Corporation, Kanagawa, Japan.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative to animal testing that focuses on protein binding. The ADRA is a skin sensitization test that solves problems associated with the direct peptide reactivity assay. However, when utilizing the ADRA to evaluate highly hydrophobic substances with octanol/water partition coefficients (logKow) of >6, the test substances may not dissolve in the reaction solution, which can prevent the accurate assessment of skin sensitization. Therefore, we developed the ADRA-organic solvent (ADRA-OS) reaction system, which is a novel skin sensitization test that enables the assessment of highly hydrophobic substances with a logKow of >6. We discovered that the organic solvent ratio, the triethylamine concentration, and the ethylenediaminetetraacetic acid disodium salt dihydrate concentration participate in reactions with the nucleophile N-(2-(1-naphthyl)acetyl)-l-cysteine (NAC) and sensitizers that are used in ADRA and in stabilizing NAC. Thus, we determined the optimal reaction composition of the ADRA-OS according to L (3 ) orthogonal array experiments. Using this test, we assessed 14 types of highly hydrophobic substances. When we compared the results with ADRA, we found that ADRA-OS reaction system has high solubility for highly hydrophobic substances and that it has a high predictive capacity (sensitivity: 63%, specificity: 100%, accuracy: 79%). The implication of the results is that the novel ADRA-OS reaction system should provide a useful method for assessing the skin sensitization of highly hydrophobic substances with a logKow of >6.
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http://dx.doi.org/10.1002/jat.4152DOI Listing
February 2021

Evaluation of subcarinal lymph node dissection and metastasis in transmediastinal radical esophagectomy.

Esophagus 2021 Feb 18. Epub 2021 Feb 18.

Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi Hirokoji, Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.

Background: The aim of the present study was to evaluate subcarinal lymph node dissection in transmediastinal radical esophagectomy and subcarinal lymph node metastasis in patients with esophageal cancer.

Methods: Three hundred and twenty-three patients with primary esophageal cancer who underwent transmediastinal or transthoracic esophagectomy with radical two- or three-field lymph node dissection were retrospectively investigated. The clinicopathological characteristics of patients with subcarinal lymph node metastasis were analyzed in detail.

Results: The median of dissected subcarinal lymph nodes in transmediastinal and transthoracic esophagectomy groups was 6 and 7, respectively, and there was no significant difference between the two groups (p = 0.12). Of all patients, 26 (8.0%) were pathologically diagnosed as positive for subcarinal lymph node metastasis, whereas only 7 (26.9%) of those with metastasis were preoperatively diagnosed as positive. In addition, all patients with subcarinal lymph node metastasis had other non-subcarinal lymph node metastasis. By univariate analysis, subcarinal lymph node metastasis was found in larger (≥ 30 mm) and deeper (T3/T4a) primary lesions (p = 0.02 and 0.02, respectively), but it was not found in 49 patients with the primary lesion located in the upper thoracic esophagus.

Conclusions: Subcarinal lymph nodes can be dissected in transmediastinal esophagectomy, almost equivalent to transthoracic esophagectomy. The tumor size, depth, and location may be predictive factors for subcarinal lymph node metastasis.
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http://dx.doi.org/10.1007/s10388-021-00824-2DOI Listing
February 2021

miRNA signaling networks in cancer stem cells.

Regen Ther 2021 Jun 29;17:1-7. Epub 2021 Jan 29.

Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.

Cancer stem cells (CSCs) are a small cell subpopulation in many cancer types and are involved in various processes of tumor progression, such as initiation, metastasis and recurrence. The distinguished features of CSCs include a variety of biological properties, including self-renewal, multidifferentiation, stemness marker expression, and resistance to chemotherapy and radiotherapy. Despite their great potential of clinical importance, the CSC signaling pathways are not well understood at the molecular level. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs that play an important role in the regulation of several cellular, physiological, and developmental processes. Aberrant miRNA expression is associated with many human diseases, including cancer. miRNAs have been implicated in the regulation of CSC properties; therefore, a better understanding of miRNA-induced modulation of CSC gene expression could aid in the identification of promising biomarkers and therapeutic targets. In the present review, we summarize the major findings of the impacts of miRNAs on CSC signaling networks; we then discuss the recent advances that have improved our understanding of CSC regulation by miRNA-mediated signaling networks and that may lead to the development of miRNA therapeutics specifically targeting CSCs.
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http://dx.doi.org/10.1016/j.reth.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848775PMC
June 2021

Anatomical resection is useful for the treatment of primary solitary hepatocellular carcinoma with predicted microscopic vessel invasion and/or intrahepatic metastasis.

Surg Today 2021 Feb 9. Epub 2021 Feb 9.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

Purpose: The aim of this study was to evaluate anatomical resection (AR) versus non-AR for primary solitary hepatocellular carcinoma (HCC) with predicted microscopic vessel invasion (MVI) and/or microscopic intrahepatic metastasis (MIM).

Methods: This retrospective study included 358 patients who underwent hepatectomy and had no evidence of MVI and/or MIM on preoperative imaging. The predictors of MVI and/or MIM were identified. The AR group (n = 222) and the non-AR group (n = 136) were classified by number of risk factor, and the survival rates were compared.

Results: Microscopic vessel invasion and/or MIM were identified in 81 (22.6%) patients. A multivariate analysis showed that high des-gamma-carboxy prothrombin concentration [odds ratio (OR) 3.35], large tumor size (OR 3.16), and high aspartate aminotransferase concentration (OR 2.13) were significant predictors. The 5-year overall survival (OS) in the patients with zero, one, two, and three risk factors were 97.4%, 73.5%, 71.5%, and 65.5%, respectively. The OS of AR is superior to that of non-AR only in patients with one or two risk factors.

Conclusion: The present findings suggest that AR should be performed for patients with one or two risk factors, and that AR may prevent recurrence, as these patients are at risk of having MVI and/or MIM.
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http://dx.doi.org/10.1007/s00595-021-02237-1DOI Listing
February 2021

Geranylgeranylacetone attenuates cerebral ischemia-reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study.

BMC Neurosci 2021 Feb 8;22(1). Epub 2021 Feb 8.

Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia-reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia-reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted.

Methods: In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography-mass spectrometry to identify ischemia-reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia-reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation.

Results: Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia-reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia-reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia-reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013).

Conclusions: As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia-reperfusion injury.
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http://dx.doi.org/10.1186/s12868-021-00614-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869466PMC
February 2021

Attention, Not Performance, Correlates With Afterdischarge Termination During Cortical Stimulation.

Front Hum Neurosci 2020 22;14:609188. Epub 2021 Jan 22.

Graduate School of Applied Informatics, University of Hyogo, Kobe, Japan.

Cortical stimulation has been used for brain mapping for over a century, and a standard assumption is that stimulation interferes with task execution due to local effects at the stimulation site. Stimulation can however produce afterdischarges which interfere with functional localization and can lead to unwanted seizures. We previously showed that (a) cognitive effort can terminate these afterdischarges, (b) when termination thus occurs, there are electrocorticography changes throughout the cortex, not just at sites with afterdischarges or sites thought functionally important for the cognitive task used, and (c) thresholds for afterdischarges and functional responses can change among stimulation trials. We here show that afterdischarge termination can occur prior to overt performance of the cognitive tasks used to terminate them. These findings, taken together, demonstrate that task-related brain changes are not limited to one or a group of functional regions or a specific network, and not limited to the time directly surrounding overt task execution. Discrete locations, networks and times importantly underpin clinical behaviors. However, brain activity that is diffuse in location and extended in time also affect task execution and can affect brain mapping. This may in part reflect fluctuating levels of attention, engagement, or motivation during testing.
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http://dx.doi.org/10.3389/fnhum.2020.609188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862320PMC
January 2021

Staging Paradox and Discrepancy in Adjuvant Chemotherapy in Patients with T4N0, T1-2N1, and T3N1 Colon Cancer.

World J Surg 2021 May 4;45(5):1561-1568. Epub 2021 Feb 4.

Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kamigyo-ku, Kyoto, 602-8566, Japan.

Background: A survival paradox between T4N0 (stage IIB/C) and T3N1 (stage IIIB) colon cancer has been rarely reported. The indication and regimen of adjuvant chemotherapy are separately described in the guidelines. This study aimed to elucidate the prognostic factors and investigate proper adjuvant treatment in colon cancer patients at these stages.

Methods: Patients who underwent R0 resection for pathological T4N0 (n = 49), T1-2N1 (n = 31), or T3N1 (n = 82) colon cancer between 2008 and 2016 at a single institute were retrospectively reviewed. The clinicopathological characteristics, status of adjuvant chemotherapy, and oncologic outcomes of patients with T4N0 tumors were compared with those of patients with T1-2N1 and T3N1 tumors.

Results: The biological characteristics of T4N0 tumors were more aggressive compared with the characteristics of T1-2N1 tumors and were similar to those of T3N1 tumors. The usage rate of oxaliplatin as an adjuvant chemotherapy was significantly lower in T4N0 patients than in T1-2N1 and T3N1 patients. The rate of local recurrence was the highest in patients with T4N0 tumors, and the survival outcomes for patients with T4N0 tumors were significantly worse compared with those of T1-2N1 patients and were similar to those of T3N1 patients. A multivariate analysis revealed that lack of adequate use of oxaliplatin for adjuvant chemotherapy was the only prognostic factor.

Conclusions: T4N0 colon cancer had similar oncological characteristics and survival outcomes to T3N1 colon cancer. Systematic adjuvant chemotherapy, including oxaliplatin, should be incorporated into the therapy for T4N0 patients as well as T3N1 patients.
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http://dx.doi.org/10.1007/s00268-021-05973-0DOI Listing
May 2021

Clinical Significance of Preoperative Albumin-Bilirubin Grade in Pancreatic Cancer.

Ann Surg Oncol 2021 Jan 23. Epub 2021 Jan 23.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Sunto-Nagaizumi, Shizuoka, Japan.

Background: No study has clarified the clinical significance of albumin-bilirubin (ALBI) grade in a large cohort of pancreatic cancer patients.

Methods: A total of 1006 consecutive patients diagnosed with pancreatic cancer and deemed eligible for surgical resection were analyzed. The ALBI score was calculated as: ALBI score = (log bilirubin [µmol/L] × 0.66) + (albumin [g/L]  × - 0.0852). ALBI grade was assigned as grade 1, 2a, 2b, and 3. ALBI grade 1 was assigned to the ALBI low group (N = 566), and grades 2a, 2b, and 3 to the ALBI high group (N = 440).

Results: The primary lesion could not be resected in 129 patients. Among all patients, overall survival (OS) was significantly worse in the ALBI high group than in the ALBI low group (P = 0.024). Overall, 877 patients underwent pancreatectomy. In these patients, the ALBI high group was associated with high CA19-9 level (P < 0.001), lower morbidity rate (P < 0.001), and pancreatic head tumor (P = 0.001). Patients' OS after resection was significantly worse in the ALBI high group than in the ALBI low group (P < 0.001). Cox proportional hazard analysis revealed ALBI grade as an independent predictor for prognosis (hazard ratio, 1.33; P = 0.015). Even in the CA19-9 negative patients, OS was significantly worse in the ALBI high group than in the ALBI low group (P = 0.046).

Conclusions: The ALBI grade is a clinically useful predictor for prognosis in pancreatic cancer patients.
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http://dx.doi.org/10.1245/s10434-021-09593-9DOI Listing
January 2021

Delivery of miR-424-5p via Extracellular Vesicles Promotes the Apoptosis of MDA-MB-231 TNBC Cells in the Tumor Microenvironment.

Int J Mol Sci 2021 Jan 15;22(2). Epub 2021 Jan 15.

Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Programmed cell death ligand-1 (PD-L1) overexpressed on cancer cells has emerged as a key inhibitor that maintains the immunosuppressive microenvironment through its interaction with the PD-1 receptor in cancer. Here, we demonstrated that miR-424-5p delivery via extracellular vesicles (EVs) derived from adipose tissue-mesenchymal stromal cells (AT-MSCs) partly promotes proinflammation and enhances antitumor cytotoxicity in vitro and in vivo. Triple negative breast cancer (TNBC) exhibits increased expression of , and is positively correlated with the overall survival of patients with TNBC. PD-L1 shows relatively higher expression in MDA-MB-231 (MM231) cells and can be downregulated by miR-424-5p. Furthermore, miR-424-5p transported by EVs can increase the secretion of proinflammatory cytokines, decrease the secretion of anti-inflammatory cytokines and promote the apoptosis of tumor cells. The intratumoral administration of miR-424-5p-EVs significantly slowed tumor growth. In conclusion, these results demonstrate that EVs may serve as a delivery system for novel immunotherapies for TNBC through the miR-424-5p/PD-L1 pathway.
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http://dx.doi.org/10.3390/ijms22020844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831022PMC
January 2021

Clinical Implication of Node-negative Resectable Pancreatic Cancer.

Ann Surg Oncol 2021 Apr 15;28(4):2257-2264. Epub 2021 Jan 15.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.

Background: Lymph node metastasis is one of the strongest prognostic factors of pancreatic cancer. However, the clinical implication of pathologically node-negative pancreatic cancer (pN0-PC) has not been fully investigated.

Methods: Patients who underwent surgical resection for radiologically resectable pancreatic cancer between 2002 and 2018 were included in this study. A clinicopathological examination focusing on pN0-PC was performed.

Results: Of all 533 patients, 155 (29.1%) were diagnosed with pN0-PC and 378 (70.9%) were diagnosed with node-positive pancreatic cancer (pN1/2-PC). The 5-year survival rates of patients with pN0-PC and pN1/2-PC were 57.1% and 25.0%, respectively (p < 0.001). A multivariate analysis revealed six prognostic factors in pN0-PC: age ≥ 70 years, nonadministration of adjuvant chemotherapy, anterior serosal invasion, nerve plexus invasion, and microscopic lymphatic and venous invasions. The 5-year survival rates of patients who had pN0-PC with 0-1 risk factor, with 2-3 risk factors, and with 4-6 risk factors were 87.6%, 47.9%, and 16.4%, respectively. Survival of patients who had pN0-PC with 4-6 risk factors was comparable to that of pN1/2 patients. The diagnostic capability of metastasis-negative lymph node was unsatisfactory, with a predictive value of < 43%.

Conclusions: Although the prognosis of patients with pN0-PC was better than that of patients with pN1/2-PC, it is not satisfactory. Survival of patients who had pN0-PC with 0-1 risk factors was extremely favorable; however, survival of patients who had pN0-PC with 4-6 risk factors was similar to those with pN1/2-PC.
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http://dx.doi.org/10.1245/s10434-020-09543-xDOI Listing
April 2021

The prognostic roles of the prognostic nutritional index in patients with intraductal papillary mucinous neoplasm.

Sci Rep 2021 Jan 12;11(1):568. Epub 2021 Jan 12.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

The preoperative accurate diagnosis is difficult in the patients with intraductal papillary mucinous neoplasm (IPMN). The aim of the present study was to elucidate the roles of systemic inflammation responses and nutritional status indexes in IPMN. High-grade dysplasia was classified as a malignant neoplasm in the study. We retrospectively reviewed 155 patients who underwent pancreatectomy. The correlation between the clinical factors and several indexes of a systemic inflammation response and nutritional status was analyzed. Among the biomarkers, prognostic nutritional index (PNI) value of malignant IPMN patients was significantly lower than that of benign IPMN patients (P = 0.023), whereas PNI was not significant predictor for malignant IPMN. The multivariate analysis showed that a PNI < 43.5 (odds ratio [OR] 16.1, 95% CI 1.88-138.5, P = 0.011) and a carbohydrate antigen (CA) 19-9 level > 22.5 U/mL (OR 6.64, 95% CI 1.73-25.6, P = 0.006) were significant independent predictors of the presence of lymph node metastasis (LNM). Our scoring system developed based on these two factors. Patients with a score of 0 had no LNM and zero disease-related death. The present study suggested the roles of PNI on the IPMN patients who undergo curative pancreatectomy.
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http://dx.doi.org/10.1038/s41598-020-79583-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803756PMC
January 2021

Tetanic stimulation of the peripheral nerve augments motor evoked potentials by re-exciting spinal anterior horn cells.

J Clin Monit Comput 2021 Jan 9. Epub 2021 Jan 9.

Department of Orthopaedic Surgery, Nara Medical University, Shijocho 840, Kashihara, Nara, 634-8521, Japan.

Tetanic stimulation of the peripheral nerve, immediately prior to conducting transcranial electrical stimulation motor evoked potential (TES-MEP), increases MEP amplitudes in both innervated and uninnervated muscles by the stimulated peripheral nerve; this is known as the remote augmentation of MEPs. Nevertheless, the mechanisms underlying the remote augmentation of MEPs remain unclear. Although one hypothesis was that remote augmentation of MEPs results from increased motoneuronal excitability at the spinal cord level, the effect of spinal anterior horn cells has not yet been investigated. We aimed to investigate the effect of tetanic stimulation of the peripheral nerve on spinal cord anterior horn cells by analyzing the F-wave. We included 34 patients who underwent elective spinal surgeries and compared the changes in F-waves and TES-MEPs pre- and post-tetanic stimulation of the median nerve. F-wave analyses were recorded by stimulating the median and tibial nerves. TES-MEPs and F-wave analyses were compared between baseline and post-tetanic stimulation time periods using Wilcoxon signed-rank tests. A significant augmentation of MEPs, independent of the level corresponding to the median nerve, was demonstrated. Furthermore, F-wave persistence was significantly increased not only in the median nerve but also in the tibial nerve after tetanic stimulation of the median nerve. The increased F-wave persistence indicates an increase of re-excited motor units in spinal anterior horn cells. These results confirm the hypothesis that tetanic stimulation of the peripheral nerve may cause remote augmentation of MEPs, primarily by increasing the excitability of the anterior horn cells.
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http://dx.doi.org/10.1007/s10877-020-00647-zDOI Listing
January 2021

Uncovering temperature-dependent extracellular vesicle secretion in breast cancer.

J Extracell Vesicles 2020 Dec 31;10(2):e12049. Epub 2020 Dec 31.

Division of Molecular and Cellular Medicine National Cancer Center Research Institute 5-1-1, Tsukiji Chuo-ku Tokyo Japan.

In all living things, temperature is a key factor to maintain function and survive. Animals and plants need to adapt temperature change with optimizing their behaviour and growth by sensing temperature. Similarly, tumour cells must adapt continuously to fluctuations in external conditions including temperature. To find a better environment, cancer cells promote growth and metastasis, which contributes to tumour malignancy. Pathological studies in breast cancer have implied that temperature is associated with disease progression. However, no clear mechanisms have emerged for how thermal changes affect tumour cells and their gene regulation in tumour development and malignancy. Here we discovered the temperature-dependent extracellular vesicle (EV) secretion in breast cancer. Cancer cell growth and EV secretion increased in a temperature-dependent manner, which indicated that temperatures were associated with poor prognosis in breast cancer patients. We also found that (), a responsible gene for temperature-dependent EV secretion, was upregulated with the increase in temperature. Consistent with our results, gene has been characterized and identified as a key factor for malignancy in a wide range of cancers. Our findings shed new light on tumour aggressiveness and therapeutic strategies for breast cancer, especially regarding EV formation and secretion, thus providing a new relationship between cancer and EV biology in the light of temperature.
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http://dx.doi.org/10.1002/jev2.12049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775566PMC
December 2020

An infected aneurysm of the vertebral artery following cervical pyogenic spondylitis: a case report and literature review.

BMC Musculoskelet Disord 2021 Jan 6;22(1):22. Epub 2021 Jan 6.

Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara City, 6348522, Nara, Japan.

Background: An important complication of pyogenic spondylitis is aneurysms in the adjacent arteries. There are reports of abdominal aortic or iliac aneurysms, but there are few reports describing infected aneurysms of the vertebral artery. Furthermore, there are no reports describing infected aneurysms of the vertebral arteries following cervical pyogenic spondylitis. We report a rare case of an infected aneurysm of the vertebral artery as a complication of cervical pyogenic spondylitis, which was successfully treated by endovascular treatment.

Case Presentation: Cervical magnetic resonance imaging (MRI) of a 59-year-old man who complained of severe neck pain showed pyogenic spondylitis. Although he was treated extensively by antibiotic therapy, his neck pain did not improve. Follow-up MRI showed the presence of a cyst, which was initially considered an abscess, and therefore, treatment initially included guided tapping and suction under ultrasonography. However, under ultrasonographic examination an aneurysm was detected. The contrast-enhanced computed tomography (CT) scan showed an aneurysm of the vertebral artery. Following endovascular treatment (parent artery occlusion: PAO), the patient's neck pain disappeared completely.

Conclusion: Although there are several reports of infected aneurysms of the vertebral arteries, this is the first report describing an infected aneurysm of the vertebral artery as a result of cervical pyogenic spondylitis. Whenever a paraspinal cyst exist at the site of infection, we recommend that clinicians use not only X-ray, conventional CT, and MRI to examine the cyst, but ultrasonography and contrast-enhanced CT as well because of the possibility of an aneurysms in neighboring blood vessels. It is necessary to evaluate the morphology of the aneurysm to determine the treatment required.
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http://dx.doi.org/10.1186/s12891-020-03881-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786991PMC
January 2021

The evaluation of the 8th and 7th edition of the American joint committee on cancer tumor classification for distal cholangiocarcinoma: the proposal of a modified new tumor classification.

HPB (Oxford) 2020 Dec 19. Epub 2020 Dec 19.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Japan.

Background: The 7th and 8th editions of the American Joint Committee on Cancer (AJCC) tumor (T) classification of distal cholangiocarcinoma (DCC), which are based on either layer or depth, may not accurately stratify patient survival.

Methods: A total of 121 patients who underwent resection for DCC between 2002 and 2016 were analyzed. The impact of the AJCC staging system on survival was examined and a new T classification was established based on independent prognostic factors.

Results: Regarding overall survival, the optimal depth of invasion (DOI) cut-off value (8 mm) was the only independent prognostic factor. Regarding the relapse-free survival (RFS), a DOI >8 mm, portal vein (PV) invasion, and duodenal or pancreatic invasion were independent prognostic factors. A new T classification was developed as follows: T1, no invasion of adjacent organs; T2, invasion of the duodenum or pancreas; T3, invasion >8 mm into the bile duct wall; and T4, invasion of the PV or arteries. There were no significant differences in RFS according to the 8th edition of the AJCC. However, significant differences were observed in the RFS between T1 and T2 and between T2 and T3.

Conclusion: A new T classification based on the layer and depth may be more feasible.
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http://dx.doi.org/10.1016/j.hpb.2020.12.001DOI Listing
December 2020

The prognostic impact of skeletal muscle status and bone mineral density for resected distal cholangiocarcinoma.

Clin Nutr 2020 Dec 15. Epub 2020 Dec 15.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan.

Background & Aims: The preoperative body composition and bone mineral density (BMD) have been reported as prognostic factors for several cancers. However, the prognostic impact of the preoperative body composition and BMD for resected distal cholangiocarcinoma (DCC) remains unclear.

Methods: A total of 111 patients who underwent pancreatoduodenectomy for DCC between 2002 and 2017 were analyzed. The skeletal muscle index (SMI) and BMD were measured by preoperative computed tomography. The optimal cut-off value of the body composition and BMD were selected based on the minimum P-value obtained by the log-rank test. The prognostic significance of the preoperative body composition and BMD was investigated using multivariate analysis.

Results: The median values of the SMI (45.7 vs. 36.7 cm/m, P < 0.001) and BMD (128.5 vs. 101.0 Hounsfield units [HU], P = 0.005) in male and female were significantly different. The optimal cut-off values for the SMI were 55 cm/m in male and 36 cm/m in female, and those for the BMD were 75 HU in male and 74 HU in female. A multivariate analysis identified low SMI (hazard ratio [HR], 4.340; P = 0.044), low BMD (HR, 5.333; P < 0.001) and microscopic venous invasion (HR, 2.019; P = 0.026) as independent prognostic factors for the survival.

Conclusions: A preoperative low SMI and low BMD were independent prognostic factors for resected DCC.
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http://dx.doi.org/10.1016/j.clnu.2020.12.011DOI Listing
December 2020

Clinical safety and efficacy of neoadjuvant combination chemotherapy of tranilast in advanced esophageal squamous cell carcinoma: Phase I/II study (TNAC).

Medicine (Baltimore) 2020 Dec;99(50):e23633

Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: Transient receptor potential vanilloid 2 (TRPV2) was previously shown to play an important role in the maintenance of cancer stem cells, and its specific inhibitor, tranilast, also has potential as a targeted therapeutic agent for esophageal squamous cell carcinoma (ESCC). The present study is being conducted to confirm the safety and efficacy of the additional use of tranilast with conventional preoperative adjuvant chemotherapy for patients with advanced ESCC.

Patients And Methods: Between 56 and 59 patients aged between 20 and 74 years with clinically diagnosed Stage II or Stage III ESCC will be enrolled. Eligible patients will receive preoperative adjuvant chemotherapy, 2 cycles of combination therapy with cisplatin, 5-fluorouracil, and tranilast. Recruitment started in November 2019, with the final follow-up being planned for March 2029. One subject has been enrolled since October 21, 2020. The pathological therapeutic effect is the primary endpoint. The objective response rate, safety of preoperative adjuvant chemotherapy, recurrence-free survival (RFS), and overall survival (OS) are the secondary endpoints. RFS and OS will be calculated as the time from surgery to first recurrence and all-cause death, respectively.

Ethics And Dissemination: This protocol has been approved by the Institutional Review Boards of Kyoto Prefectural University of Medicine and all participating hospitals in August 30, 2019 (Number: CRB5180001). Written informed consent will be obtained from all patients before their registration, which is in accordance with the Declaration of Helsinki. The results of the present study will be disseminated via publication in peer-reviewed journals.

Trial Registration: Trial registration number jRCTs051190076.
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http://dx.doi.org/10.1097/MD.0000000000023633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738016PMC
December 2020

Description of the Vascular Anatomy of Livers with Absence of the Portal Bifurcation.

World J Surg 2021 Mar 9;45(3):833-840. Epub 2020 Nov 9.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Background: The absence of the portal bifurcation (APB) is a rare anatomic variation, in which the horizontal part of the left portal vein (PV) is missing. The aim of this study was to identify the vascular architecture in livers with APB.

Methods: Computed tomography data for 17,651 patients were reviewed; five patients (0.03%) were found to present with APB. The liver volume and anatomy of APB patients were compared with those of 30 patients with normal livers.

Results: All the APB patients exhibited an independent posterior branch of the PV. The intrahepatic left PV (LPV) ran through either the ventral (n = 2, 40%) or dorsal side (n = 3, 60%) of the middle hepatic vein. The frequency of medial branches diverging from the LPV was higher in patients with APB than in normal patients (p < 0.001). The left hepatic duct (LHD) ran through the inside of the left lobe along the left PV in 40% of the patients with APB, whereas in the remaining 60% of the patients with APB, the LHD ran on the outside of the liver separately from the left PV and joined the right hepatic duct. The liver volume of the left lateral section was significantly smaller (p = 0.014), and the posterior section was significantly larger (p = 0.014) in patients with APB than in patients with normal livers.

Conclusion: The unique anatomical characteristics and the positional relation of the vessels should be considered preoperatively in patients with APB.
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http://dx.doi.org/10.1007/s00268-020-05848-wDOI Listing
March 2021

Analysis of right-sided ligamentum teres: The novel anatomical findings and classification.

J Hepatobiliary Pancreat Sci 2021 Feb 17;28(2):221-230. Epub 2020 Nov 17.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.

Background: The true anatomy of right-sided ligamentum teres (RSLT) has not been fully explained for a century. This study aimed to clarify the exact anatomy of RSLT.

Methods: The computed tomography data of 17 651 surgical patients were observed and 76 patients with RSLT, were classified into the bilateral ligamentum teres (LT) group (type A) and three RSLT groups, (B) bifurcation type, (C) trifurcation type, and (D) independent posterior branch type.

Results: Type A had double LT that connected to both the right and left sides of the umbilical portion (UP). Types B-D had a P3 + 4 rather than a left UP. Type D was anatomically different from types A-C. Upon comparing types A-C and type D, type D had a significantly smaller volume of segments 3 + 4 (P < .001), and the UP was more often on the left side. The position of the gallbladder fundus in type D was more commonly observed on the right side of the LT compared with that observed in the other types (P = .007).

Conclusions: The change in the volume of segments 3 + 4 and the extent of the RSLT shift create a false perception that the gallbladder changes the position.
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http://dx.doi.org/10.1002/jhbp.856DOI Listing
February 2021

Improving predictive capacity of the Amino acid Derivative Reactivity Assay test method for skin sensitization potential with an optimal molar concentration of test chemical solution.

J Appl Toxicol 2021 Feb 30;41(2):303-329. Epub 2020 Oct 30.

Safety Evaluation Center, Fujifilm Corporation, Kanagawa, Japan.

The Amino acid Derivative Reactivity Assay (ADRA) is a convenient and effective in chemico test method for assessing covalent binding of test chemicals with protein-derived nucleophilic reagents as a means of predicting skin sensitization potential. Although the original molar-concentration approach to ADRA testing was not suitable for testing multiconstituent substances of an unknown composition, a weight-concentration approach that is suitable for such substances was developed, which also led to the realization that test chemical solutions prepared to molar concentrations higher than the original 1 mM would reduce false negative results as well as enhance predictive capacity. The present study determined an optimal molar-concentration that achieves even higher predictive capacity than the original ADRA. Eight chemicals that were false negatives when tested with 1 mM test chemical solutions were retested with test chemical solutions between 2 and 5 mM, which showed 4 mM to be the optimal molar-concentration for ADRA testing. When 82 chemicals used in the original development were retested with 4 mM test chemical solutions, false negative results were reduced by four. When an additional 85 chemicals used to evaluate the weight-concentration approach to ADRA were retested, the results essentially replicated those obtained with 0.5 mg/ml test chemical solutions and gave 10 fewer false negatives than original ADRA with 1 mM solutions. A comparison of these results for 136 chemicals showed that ADRA testing with 4 mM solutions achieved a four percentage point improvement in accuracy over original ADRA and a two percentage point improvement over DPRA testing.
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http://dx.doi.org/10.1002/jat.4082DOI Listing
February 2021

The influence of familial pancreatic cancer on postoperative outcome in pancreatic cancer: relevance to adjuvant chemotherapy.

J Gastroenterol 2021 Jan 22;56(1):101-113. Epub 2020 Oct 22.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

Background: Familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The prognostic significance of PC in an FPC family after surgery is not fully understood.

Methods: This was a retrospective study of 427 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2008 and December 2016. PC patients who also had at least one first-degree relative with PC were defined as FPC patients. The associations between recurrence and clinicopathological characteristics were analyzed for both FPC and non-FPC patients.

Results: FPC patients accounted for 31 of the 427 (7.3%) patients. Recurrence occurred in 72.1% of the total cohort and in 87.1% of the 31 FPC patients. Multivariate analysis showed that being an FPC patient was an independent predictor for relapse-free survival (RFS) (hazard ratio [HR] 1.52, P = 0.038). Although univariate analysis revealed that being an FPC patient was significantly associated with poorer overall survival (OS) (P < 0.001), multivariate analysis showed that being an FPC patient was not an independent predictor for OS (P = 0.164). Dichotomization of the 427 patients into those who received (n = 317: 17 FPC and 300 non-FPC patients) and did not receive (n = 110: 14 FPC and 96 non-FPC patients) adjuvant chemotherapy revealed that being an FPC patient was an independent predictor for RFS (HR 2.50, P < 0.001) and OS (HR 2.30, P = 0.003) only for patients who received adjuvant chemotherapy.

Conclusions: This study has shown that being an FPC patient is a significant prognostic indicator for PC patients who undergo resection and receive adjuvant chemotherapy.
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http://dx.doi.org/10.1007/s00535-020-01730-7DOI Listing
January 2021

Analysis of serum lysophosphatidylethanolamine levels in patients with non-alcoholic fatty liver disease by liquid chromatography-tandem mass spectrometry.

Anal Bioanal Chem 2021 Jan 22;413(1):245-254. Epub 2020 Oct 22.

Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, 060-0812, Japan.

Lysophosphatidylethanolamines (LysoPEs) are the partial hydrolysis products of phosphatidylethanolamine. Despite the unique in vitro bioactivities of LysoPEs, there are limited reports on the pathophysiological role of LysoPEs in the serum, due to the lack of sensitive analytical methods for determination of each molecular species in clinical samples. Herein, we developed a highly sensitive quantitative method to profile the serum LysoPE species by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring (SRM). The internal standard (IS), chemically synthesized in-house, and the lineup of seven major LysoPE species were used in this study. The limits of detection and quantification for each LysoPE species ranged within 0.5-3.3 pmol/mL and 1.0-5.0 pmol/mL, respectively. The combined concentrations of LysoPEs in the serum from healthy subjects (n = 8) and the patients with non-alcoholic fatty liver diseases (NAFLD) including simple steatosis (SS, n = 9) and non-alcoholic steatohepatitis (NASH, n = 27) were 18.030 ± 3.832, 4.867 ± 1.852, and 5.497 ± 2.495 nmol/mL, respectively. The combined and individual concentrations of LysoPEs, except for LysoPE 18:0, significantly decreased in the patients with NAFLD compared with those for the healthy subjects. However, no significant difference was observed between the SS and NASH groups. Our proposed LC-MS/MS method is valid and has advantages of small sample volume, high sensitivity, and simultaneous absolute quantitation for multiple molecular species. This method may enable diagnostic evaluation and elucidation of the as-yet uncovered pathophysiological role of LysoPEs.
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http://dx.doi.org/10.1007/s00216-020-02996-9DOI Listing
January 2021