Phase II randomized controlled trial to evaluate the supportive effect of Koujin (TJ-3020) powder in gemcitabine and nab-paclitaxel-treated unresectable or recurrent pancreatic cancer.

Objectives: Gemcitabine and nab-paclitaxel combination therapy (GnP) is a standard treatment for unresectable or recurrent pancreatic cancer. However, fatigue and malaise are frequent adverse effects. Recently, Kampo medicine containing ginsenoside has been reported to relieve cancer-related fatigue.

Prognostic Impact of Mutations Associated With Smoking and Drinking History in Japanese Digestive Cancers.

Background/aim: Organs of the digestive system are frequent sites of cancer development, and digestive tract cancers are the leading causes of death worldwide, including in Japan. Most of these cancers are associated with smoking or drinking habits. This study focused on the clinical and genomic characteristics of patients with these cancers using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which comprises a large volume of data on Japanese patients who have undergone tumor profiling gene panel tests.

Protocol for high-quality single-cell RNA-seq from tissue sections with DRaqL.

Single-cell RNA sequencing (scRNA-seq) combined with laser capture microdissection (LCM) offers a versatile framework for comprehensive transcriptomics from tissue sections. Here, we present a detailed protocol for DRaqL (direct RNA recovery and quenching for LCM) in combination with Smart-seq2 (DRaqL-Smart-seq2), which enables high-quality RNA sequencing for single cells obtained from alcohol-fixed murine ovarian sections. Additionally, we provide an optional procedure for scRNA-seq from formalin-fixed sections (DRaqL-Protease-Smart-seq2).

Production of [At]NaAt solution under GMP compliance for investigator-initiated clinical trial.

Background: The alpha emitter astatine-211 (At) is garnering attention as a novel targeted alpha therapy for patients with refractory thyroid cancer resistant to conventional therapy using beta emitter radioiodine (I). Herein, we aimed to establish a robust method for the manufacturing and quality control of [At]NaAt solution for intravenous administration under the good manufacturing practice guidelines for investigational products to conduct an investigator-initiated clinical trial.

Results: At was separated and purified via dry distillation using irradiated Bi plates containing At obtained by the nuclear reaction of Bi(He, 2n)At.

Financial burden of surgical treatment for retroperitoneal sarcoma.

Purposes: The purpose of this study was to compare the financial burden of surgery for retroperitoneal sarcoma (RPS) and gastric cancer (GC).

Methods: All patients who underwent surgery for GC or RPS between 2020 and 2021 at Nagoya University Hospital were included. The clinical characteristics, surgical fees per surgeon, and surgical fees per hour were compared between the two groups.

DPPA3 facilitates genome-wide DNA demethylation in mouse primordial germ cells.

Background: Genome-wide DNA demethylation occurs in mammalian primordial germ cells (PGCs) as part of the epigenetic reprogramming important for gametogenesis and resetting the epigenetic information for totipotency. Dppa3 (also known as Stella or Pgc7) is highly expressed in mouse PGCs and oocytes and encodes a factor essential for female fertility. It prevents excessive DNA methylation in oocytes and ensures proper gene expression in preimplantation embryos: however, its role in PGCs is largely unexplored.

Risk Factors for Long-term Body Weight Loss After Proximal Gastrectomy: A Retrospective Analysis.

Background/aim: Proximal gastrectomy (PG) is a therapy for early-stage proximal gastric cancer and offers advantages such as the preservation of food storage capacity and less body weight loss (BWL). Nevertheless, significant BWL following PG may occur, affecting the patient's well-being and survival. In this study, we aimed to identify the relevant factors for BWL following PG by analyzing an institutional database of patients.

Immuno-PET and Targeted α-Therapy Using Anti-Glypican-1 Antibody Labeled with Zr or At: A Theranostic Approach for Pancreatic Ductal Adenocarcinoma.

Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed to evaluate the potential of an anti-GPC1 monoclonal antibody (GPC1 mAb) labeled with Zr or At as a theranostic target in pancreatic ductal adenocarcinoma. GPC1 mAb clone 01a033 was labeled with Zr or At with a deferoxamine or decaborane linker, respectively.

Predictive impacts of peritoneal washing cytology for surgical resection-intended pancreatic cancer cases: Establishment of planned staging laparoscopy criteria.

Background: Staging laparoscopy (SL) has been advocated for pancreatic cancer, mainly to evaluate the peritoneal washing cytology (CY) status, which seems to impact the prognosis of pancreatic cancer. To establish an optimal treatment strategy for CY positive (CY+) pancreatic cancer cases, real-world clinical data about CY status-depending surgical outcomes should be accumulated.

Methods: Peritoneal washing samples were collected from 183 consecutive patients who could be classified as either resectable or borderline resectable (BR) pancreatic cancer between January 2012 and December 2020.

Evaluation of LAT1 Expression in Patients With Lung Cancer and Mediastinal Tumors: 18F-FBPA PET Study With Immunohistological Comparison.

Purpose Of The Report: L-type amino acid transporter-1 (LAT1) is a tumor-specific transporter expressed in various tumor types, with minimal expression in normal organs. We previously demonstrated 18F-fluoro-borono-phenylalanine (18F-FBPA) as a selective PET probe for LAT1 in a preclinical study. Herein, we evaluated LAT1 expression in preoperative patients with lung or mediastinal tumors using 18F-FBPA PET and immunofluorescence staining.

Rat post-implantation epiblast-derived pluripotent stem cells produce functional germ cells.

In mammals, pluripotent cells transit through a continuum of distinct molecular and functional states en route to initiating lineage specification. Capturing pluripotent stem cells (PSCs) mirroring pluripotent states provides accessible models to study the pluripotency program and mechanisms underlying lineage restriction. Here, we develop optimal culture conditions to derive and propagate post-implantation epiblast-derived PSCs (EpiSCs) in rats, a valuable model for biomedical research.

High Preoperative Serum D-dimer Predicts Unfavorable Survival Outcomes for Pancreatic Cancer Patients.

Background/aim: Pancreatic cancer cells release certain tissue factors into the bloodstream. It is well known that pancreatic cancer progresses with thrombus formation. Because we routinely measure serum D-dimer levels in preoperative patients as a screening marker of deep venous thrombosis, we examined its association with high serum D-dimer in our cohort of pancreatic cancer resected cases.

Albumin-Globulin Ratio Indicates the Survival Outcome of Pancreatic Cancer Cases Who Underwent Preoperative Treatment and Curative Surgical Resection.

Background: The pretreatment albumin-globulin ratio (AGR) is a frequently used inflammation-associated factor that has been reported to have associations with the survival outcomes of various malignancies.

Methods: We retrospectively analyzed 162 patients with pancreatic cancer who underwent preoperative treatment followed by curative surgery at Nagoya University Hospital between April 2010 and December 2020. Representative nutritional status indicators of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin-globulin ratio (AGR) were calculated for each case.

Cohesin controls X chromosome structure remodeling and X-reactivation during mouse iPSC-reprogramming.

Reactivation of the inactive X chromosome is a hallmark epigenetic event during reprogramming of mouse female somatic cells to induced pluripotent stem cells (iPSCs). This involves global structural remodeling from a condensed, heterochromatic into an open, euchromatic state, thereby changing a transcriptionally inactive into an active chromosome. Despite recent advances, very little is currently known about the molecular players mediating this process and how this relates to iPSC-reprogramming in general.

Advantages of FBPA PET in evaluating early response of anti-PD-1 immunotherapy in B16F10 melanoma-bearing mice: Comparison to FDG PET.

Purpose: PET with L-4-borono-2-[F] fluoro-phenylalanine (FBPA) was reported to be useful to differentiate malignant tumors and inflammation. Although immunotherapy with immune checkpoint inhibitors (ICIs) has been applied to cancer treatment recently, FDG PET may not be suitable to determine the effect of ICIs because of false-positive findings caused by treatment-related inflammation. In this study, we aimed to demonstrate that FBPA PET allowed detection of the early response of anti-PD-1 immunotherapy in tumor-bearing mice, comparing the results with those of FDG PET.

Comparison Between FOLFIRINOX and nal-IRI/FL as Second-line Treatment After Gemcitabine Plus Nab-paclitaxel for Pancreatic Cancer.

Background/aim: The regimen of nanoliposomal irinotecan plus 5-fluorouracil and leucovorin (Nal-IRI/FL) was approved in Japan as second-line chemotherapy after gemcitabine-based treatment for pancreatic ductal adenocarcinoma (PDAC) in 2020. We examined the difference in outcome between patients treated with second-line folinic acid, fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX) and those treated with nal-IRI/FL after first-line gemcitabine and nab-paclitaxel (GnP).

Patients And Methods: The outcomes of 34 patients with PDAC who received second-line FOLFIRINOX (n=21) or nal-IRI/FL (n=13) after GnP at our Department from January 2016 to June 2021 were reviewed retrospectively.

Downregulation of ROBO4 in Pancreatic Cancer Serves as a Biomarker of Poor Prognosis and Indicates Increased Cell Motility and Proliferation Through Activation of MMP-9.

Background: The axon guidance gene family, SLIT/ROBO pathway, controls neural network formation, which correlates with the development of several cancers.

Methods: We found through analysis of the public database that ROBO4, one of the axon guidance molecules among the SLIT/ROBO family, is significantly downregulated in primary pancreatic cancer tissues compared with adjacent normal tissues. We carried out transfection experiments using three pancreatic cancer cell lines (MiaPaCa-2, BxPC-3, and SW1990) and one pancreatic duct epithelial cell line (HPDE6c7).

Functional primordial germ cell-like cells from pluripotent stem cells in rats.

The in vitro generation of germ cells from pluripotent stem cells (PSCs) can have a substantial effect on future reproductive medicine and animal breeding. A decade ago, in vitro gametogenesis was established in the mouse. However, induction of primordial germ cell-like cells (PGCLCs) to produce gametes has not been achieved in any other species.

Impact of molecular surgical margin analysis on the prediction of pancreatic cancer recurrences after pancreaticoduodenectomy.

Background: Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins.

One-pot and one-step automated radio-synthesis of [F]AlF-FAPI-74 using a multi purpose synthesizer: a proof-of-concept experiment.

Background: Fibroblast activation protein (FAP) is overexpressed in the stroma of many types of cancer. [F]AlF-FAPI-74 is a positron emission tomography tracer with high selectivity for FAP, which has already shown high accumulation within human tumors in clinical studies. However, [F]AlF-FAPI-74 radiosynthesis has not been optimized using an automated synthesizer.

Extended single-dose toxicity study of [At]NaAt in mice for the first-in-human clinical trial of targeted alpha therapy for differentiated thyroid cancer.

Objective: Astatine (At) is a promising alpha emitter as an alternative to iodine (I). We are preparing the first-in-human (FIH) clinical trial of targeted alpha therapy for differentiated thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed an extended single-dose toxicity examination under a reliability standard, as a preclinical safety assessment of [At]NaAt to determine the FIH dose.