The IRDiRC Chrysalis Task Force: making rare disease research attractive to companies.

Background: The International Rare Diseases Research Consortium (IRDiRC) is an international initiative that aims to use research to facilitate rapid diagnosis and treatment of rare diseases.

Objective: IRDiRC launched the Chrysalis Task Force to identify key financial and nonfinancial factors that make rare disease research and development attractive to companies.

Methods: The Chrysalis Task Force was comprised of thought leaders from companies, patient advocacy groups, regulatory agencies, and research funders.

Early symptoms preceding post-infectious irritable bowel syndrome following COVID-19: a retrospective observational study incorporating daily gastrointestinal symptoms.

Background: Intestinal microinflammation with immune dysfunction due to severe acute respiratory syndrome coronavirus 2 reportedly precipitates post-infectious irritable bowel syndrome. This study aimed to elucidate potential risk factors for subsequent development of irritable bowel syndrome, hypothesizing that it is associated with specific symptoms or patient backgrounds.

Methods: This single-center retrospective observational study (2020-2021) included adults with confirmed coronavirus disease requiring hospital admission and was conducted using real-world data retrieved from a hospital information system.

Threshold of increase in oxygen demand to predict mechanical ventilation use in novel coronavirus disease 2019: A retrospective cohort study incorporating restricted cubic spline regression.

Background: Rapid deterioration of oxygenation occurs in novel coronavirus disease 2019 (COVID-19), and prediction of mechanical ventilation (MV) is needed for allocation of patients to intensive care unit. Since intubation is usually decided based on varying clinical conditions, such as required oxygen changes, we aimed to elucidate thresholds of increase in oxygen demand to predict MV use within 12 h.

Methods: A single-center retrospective cohort study using data between January 2020 and January 2021was conducted.

Survey Results and Recommendations from Japanese Stakeholders for Good Clinical Practice Renovation.

Background: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders.

Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma.

Background: In Japan and South Korea, transarterial chemoembolisation (TACE) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown effective and safe in patients with advanced HCC. This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE.

Adenovirus vectors with chimeric type 5 and 35 fiber proteins exhibit enhanced transfection of human pancreatic cancer cells.

Adenovirus (Ad) vectors are widely used for gene transfer. Efficient gene transfer into malignant cells is an important requirement for anticancer gene therapy, but transgene expression after transfer with adenoviral vectors varies among different cancer cell lines. Recently, Ad vectors containing chimeric type 5 and 35 fiber proteins have been developed.

Midkine promoter-based conditionally replicative adenovirus therapy for midkine-expressing human pancreatic cancer.

Background: To develop a novel therapeutic strategy for human pancreatic cancer using a midkine promoter-based conditionally replicating adenovirus.

Methods: We examined midkine mRNA expression and midkine protein expression by seven human pancreatic cancer cell lines (AsPC-1, BxPC-3, CFPAC-1, HPAC, MIAPaCa-2, PANC-1, and Suit-2), as well as by non-cancerous pancreatic tissue and pancreatic cancers. Midkine promoter activity was measured in cancer cell lines by the dual luciferase reporter assay.

Prognostic implication of para-aortic lymph node metastasis in resectable pancreatic cancer.

Background: The survival curve of patients who undergo surgical resection of pancreatic cancer displays a steep decline within 1 year and a relatively slow decline thereafter. The patients with a short survival time may have identifiable clinicopathologic factors that lead to rapid relapse.

Study Design: We analyzed clinicopathologic factors in 133 patients who underwent margin-negative pancreatoduodenectomy with extended radical lymphadenectomy for invasive ductal carcinoma of the pancreas to detect factors that could be responsible for the short survival.

Gallbladder cancer in a patient with Miller-Dieker syndrome.

Unlabelled: We report the case of a male patient with Miller-Dieker syndrome (MDS) and gallbladder cancer. Chromosome analysis by fluorescence in situ hybridization revealed a deletion in the 17p13.3 region, an area thought to contain tumour suppressor genes, including the hypermethylated in cancer 1 gene.

Downregulation of survivin by siRNA diminishes radioresistance of pancreatic cancer cells.

Background: Survivin is a member of the inhibitor of apoptosis protein family, which inhibits apoptosis and regulates cell division. Survivin is expressed by the majority of human cancers, including pancreatic adenocarcinoma. We have reported that its expression is correlated with shorter survival of pancreatic cancer patients, so regulation of this molecule could be a new strategy for fighting pancreatic cancer.

Analysis of E-, N-cadherin, alpha-, beta-, and gamma-catenin expression in human pancreatic carcinoma cell lines.

Objectives: Cadherins are cell surface glycoproteins that mediate Ca2+-dependent, homophilic cell-cell adhesion. The classic cadherins interact with either beta-catenin or gamma-catenin, which is bound to alpha-catenin that links the complex to the actin cytoskeleton. It has been reported that alteration in cadherins/catenins function or expression is found in the neoplastic process as a step in metastasis.

Survivin expression is a prognostic marker in pancreatic cancer patients.

Background: In this study, we assessed survivin expression in pancreatic cancer specimens from patients who underwent either pancreatic resection alone or pancreatic resection plus postoperative radiation therapy (PORT) to evaluate whether survivin expression is predictive of sensitivity to PORT and outcome in pancreatic cancer patients.

Methods: Fifty-two patients who underwent pancreatic resection for ductal adenocarcinomas were included in this study. Forty-seven pancreatic ductal adenocarcinoma and 5 normal pancreatic tissues were evaluated for survivin expression by immunohistochemistry.

N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma.

Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion. In the present study, E- and N-cadherin, members of the classical cadherin family, are investigated as inducers of epithelial-to-mesenchymal transition (EMT) that is thought to play a fundamental role during the early steps of invasion and metastasis of carcinomas. Cell growth factors are known to regulate cell adhesion molecules.

Pancreatic endocrine tumor in Japan.

Japanese clinicians and scientists have contributed significantly to reporting, investigating, and managing patients with pancreatic endocrine tumors and other multiple endocrine neoplasias for the past several decades. This article summarizes the latest progress in this field in Japan. Particularly, our contribution to the development of diagnostic and localization methods is reviewed.

RECK expression in pancreatic cancer: its correlation with lower invasiveness and better prognosis.

Background: The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene was initially isolated as a transformation suppressor gene. The RECK gene is expressed widely in normal organs but is undetectable in many tumor-derived cell lines. When artificially expressed in such cell lines, RECK negatively regulates at least matrix metalloprotease (MMP)-9, MMP-2, and MT1-MMP activation and suppresses the invasive and metastatic potentials of these cells.

Intravenous calcium injection test is a novel complementary procedure in differential diagnosis for gastrinoma.

The current study evaluated efficacy of the intravenous calcium injection test as a new diagnostic approach to clarify the existence of gastrinoma, which often goes undetected with routine testing. Twenty-six patients with hypergastrinemia were studied. For the calcium injection test, blood samples were taken from 12 patients with hypergastrinemia (HG), and three healthy volunteers, and one patient with nonfunctioning endocrine tumor in the pancreas (control).

Expression of integrin alphaVbeta3 in pancreatic carcinoma: relation to MMP-2 activation and lymph node metastasis.

Introduction: Overexpression of integrin alphaVbeta3 had been demonstrated in various tumors. Studies have suggested that elevated levels of integrin alphaVbeta3 in melanoma cells are deeply involved in the mechanism of increased melanoma invasiveness.

Aims: To examine the expression of integrin alphaVbeta3 in pancreatic carcinoma and to evaluate the correlation between integrin expression accompanied by MMP-2 activation and clinicopathologic factors.

Surgical management of intraductal papillary mucinous tumor of the pancreas.

Background: Intraductal papillary mucinous tumor (IPMT) is a type of pancreatic cystic neoplasm. IPMT consists of intraductal papillary mucinous adenoma (benign IPMT) and intraductal papillary mucinous carcinoma (malignant IPMT). Preoperative diagnosis of malignancy is difficult; the invasiveness and metastatic character are not well known.

[Current status of adjuvant therapy for pancreatic cancer].

Pancreatic cancer is considered to be one of the malignancies most resistant to therapy. It is characterized by early local invasion and distant spread. Therefore, resection with curative intent is limited to a very small proportion of patients.

Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer.

Unlabelled: Recently, some studies have shown that delayed scanning with (18)F-FDG PET may help to differentiate malignant from benign pancreatic lesions. However, no study has evaluated the relationship between temporal changes in (18)F-FDG uptake and expression of hexokinase or glucose transporter.

Methods: Twenty-one consecutive patients with pancreatic cancer were studied preoperatively by dual-phase (18)F-FDG PET, performed 1 and 2 h after injection of (18)F-FDG.