tbuckley/cabot-search huggingface dataset:
Targeting the activated microenvironment with endosialin (CD248)-directed CAR-T cells ablates perivascular cells to impair tumor growth and metastasis
Authors: Sarah L Ash, Rebecca Orha, Holly Mole, Meg Dinesh-Kumar, Steven P Lee, Frances K Turrell, Clare M Isacke
Journal: Journal for ImmunoTherapy of Cancer (2024)

Targeting of solid cancers with chimeric antigen receptor (CAR)-T cells is limited by the lack of suitable tumor-specific antigens and the immunosuppressive, desmoplastic tumor microenvironment that impedes CAR-T cell infiltration, activity and persistence. We hypothesized that targeting the endosialin (CD248) receptor, strongly expressed by tumor-associated pericytes and perivascular cancer-associated fibroblasts, would circumvent these challenges and offer an exciting antigen for CAR-T cell therapy due to the close proximity of target cells to the tumor vasculature, the limited endosialin expression in normal tissues and the lack of phenotype observed in endosialin knockout mice. We generated endosialin-directed E3K CAR-T cells from three immunocompetent mouse strains, BALB/c, FVB/N and C57BL/6. E3K CAR-T cell composition (CD4+/CD8+ ratio), activity in vitro against endosialin+ and endosialin- cells, and expansion and activity in vivo in syngeneic tumor models as well as in tumor-naive healthy and wounded mice and tumor-bearing endosialin knockout mice was assessed. E3K CAR-T cells were active in vitro against both mouse and human endosialin+, but not endosialin-, cells. Adoptively transferred E3K CAR-T cells exhibited no activity in endosialin knockout mice, tumor-naive endosialin wildtype mice or in wound healing models, demonstrating an absence of off-target and on-target/off-tumor activity. By contrast, adoptive transfer of E3K CAR-T cells into BALB/c, FVB/N or C57BL/6 mice bearing syngeneic breast or lung cancer lines depleted target cells in the tumor stroma resulting in increased tumor necrosis, reduced tumor growth and a substantial impairment in metastatic outgrowth. Together these data highlight endosialin as a viable antigen for CAR-T cell therapy and that targeting stromal cells closely associated with the tumor vasculature avoids CAR-T cells having to navigate the harsh immunosuppressive tumor microenvironment. Further, the ability of E3K CAR-T cells to recognize and target both mouse and human endosialin+ cells makes a humanized and optimized E3K CAR a promising candidate for clinical development applicable to a broad range of solid tumor types.
<i>Salmonella</i>-mediated methionine deprivation drives immune activation and enhances immune checkpoint blockade therapy in melanoma
Authors: Sujin Zhou, Shiwei Zhang, Kexin Zheng, Zixuan Li, Enyu Hu, Yunping Mu, Jialuo Mai, Allan Zhao, Zhenggang Zhao, Fanghong Li
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Although immune checkpoint inhibitor (ICI)-based therapy is advantageous for patients with advanced melanoma, resistance and relapse are frequent. Thus, it is crucial to identify effective drug combinations and develop new therapies for the treatment of melanoma. SGN1, a genetically modified Salmonella typhimurium species that causes the targeted deprivation of methionine in tumor tissues, is currently under investigation in clinical trials. However, the inhibitory effect of SGN1 on melanoma and the benefits of SGN1 in combination with ICIs remain largely unexplored. Therefore, this study aims to investigate the antitumor potential of SGN1, and its ability to enhance the efficacy of antibody-based programmed cell death-ligand 1 (PD-L1) inhibitors in the treatment of murine melanoma. Methods The antitumor activity of SGN1 and the effect of SGN1 on the efficacy of PD-L1 inhibitors was studied through murine melanoma models. Further, The Cancer Genome Atlas-melanoma cohort was clustered using ConsensusClusterPlus based on the methionine deprivation-related genes, and immune characterization was performed using xCell, Microenvironment Cell Populations-counter, Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data, and immunophenoscore (IPS) analyses. The messenger RNA data on programmed death-1 (PD-1) immunotherapy response were obtained from the Gene Expression Omnibus database. Gene Set Enrichment Analysis of methionine deprivation-up gene set was performed to determine the differences between pretreatment responders and non-responders. Results This study showed that both, the intratumoral and the intravenous administration of SGN1 in subcutaneous B16-F10 melanomas, suppress tumor growth, which was associated with an activated CD8+T-cell response in the tumor microenvironment. Combination therapy of SGN1 with systemic anti-PD-L1 therapy resulted in better antitumor activity than the individual monotherapies, respectively, and the high therapeutic efficacy of the combination was associated with an increase in the systemic level of tumor-specific CD8 + T cells. Two clusters consisting of methionine deprivation-related genes were identified. Patients in cluster 2 had higher expression of methionine_deprivation_up genes, better clinical outcomes, and higher immune infiltration levels compared with patients in cluster 1. Western blot, IPS analysis, and immunotherapy cohort study revealed that methionine deficiency may show a better response to ICI therapy Conclusions： This study reports Salmonella -based SGN1 as a potent anticancer agent against melanoma, and lays the groundwork for the potential synergistic effect of ICIs and SGN1 brought about by improving the immune microenvironment in melanomas.
Inspection of intraductal papillary mucinous neoplasm via the papilla using a novel slim pancreatoscope under balloon enteroscopy
Authors: Yuki Tanisaka, Masafumi Mizuide, Akashi Fujita, Takahiro Shin, Kei Sugimoto, Ryuhei Jinushi, Shomei Ryozawa
Journal: Endoscopy (2024)

Peroral pancreatoscopy (POPS) is useful for the direct visualization of intraductal lesions in the pancreatic duct [1] [2] [3]. However, POPS in patients with Roux-en-Y anastomosis via the papilla under balloon enteroscopy is difficult because pancreatoscopes are approximately 10 Fr in diameter and cannot pass through the forceps channel of the balloon enteroscope. We report a successful inspection of an intraductal papillary mucinous neoplasm (IPMN) using a novel slim pancreatoscope under balloon enteroscopy in a patient with Roux-en-Y gastrectomy.
Endoscopic ultrasound-guided drainage using a forward-viewing echoendoscope for peripancreatic fluid collection after Child resection
Authors: Takuya Ishikawa, Kentaro Yamao, Yasuyuki Mizutani, Tadashi Iida, Kota Uetsuki, Masanao Nakamura, Hiroki Kawashima
Journal: Endoscopy (2024)

Peripancreatic fluid collection (PFC) due to pancreatic leakage is one of the significant complications arising following pancreatic surgery. Although endoscopic ultrasound (EUS)-guided drainage is less invasive than other methods in treating PFCs, it requires the drainage area to be in contact with the gastrointestinal tract accessible by the echoendoscope [1]. In patients with surgically altered anatomy, an oblique-viewing echoendoscope, which is mainly used for EUS-guided drainage, encounters technical difficulties in the jejunum. Recently, the usefulness of a forward-viewing echoendoscope in such cases has been reported [2] [3].
Remarkable tumor shrinkage in hilar biliary cholangiocarcinoma confirmed by peroral cholangioscopy following neoadjuvant chemotherapy
Authors: Ko Tomishima, Akinori Suzuki, Koichi Ito, Shigeto Ishii, Toshio Fujisawa, Yuki Fukumura, Hiroyuki Isayama
Journal: Endoscopy (2024)

Neoadjuvant chemotherapy is considered an effective strategy for patients with advanced biliary tract cancer for improving R0 resection and prognosis [1]. We report a complete pathological response with remarkable biliary tumor shrinkage on peroral cholangioscopy (POCS) both before and after neoadjuvant chemotherapy.
Endoscopic management of a chronic anastomotic leak after a Billroth II procedure
Authors: Reid D. Wasserman, William F. Abel, Arnold Salzberg, Vivek Kesar, Paul Yeaton, Varun Kesar
Journal: Endoscopy (2024)

We report the case of a 56-year-old woman with a pertinent past medical history of chronic pancreatitis and peptic ulcer disease, who initially presented with a perforated posterior duodenal ulcer following a Billroth II procedure, which was complicated by a duodenal stump abscess and purulent free fluid in the pelvis. The patient subsequently underwent a computed tomography (CT) scan of the abdomen, which revealed extraluminal contrast extravasation within the left upper quadrant, raising concern of an anastomotic leak ([Fig. 1]). The patient subsequently underwent upper gastrointestinal endoscopy with argon plasma coagulation (APC) and full-thickness endoscopic suturing, with placement of a nasojejunal tube (NJT) in the efferent jejunal limb ([Fig. 2]; [Video 1]). An upper gastrointestinal series was performed the next day, which showed no evidence of residual leakage ([Fig. 3]). The patient was discharged with instructions to remain nil by mouth, and an NJT for tube feeding, along with oral antibiotics. Subsequently, she was started on an oral diet and tolerated this without any complications. At follow-up, 3 months after the procedure, the patient was tolerating solid food well.
Stretching the limits of submucosal tunneling endoscopic resection
Authors: Diogo Bernardo Moura, Nuno Nunes, Maria Antónia Duarte
Journal: Endoscopy (2024)

A 60-year-old man presented with dysphagia due to a 40-mm leiomyoma of the muscularis propria in the middle third of the esophagus. The patient had a history of hypertension, atrial fibrillation, and anticoagulation. Endoscopic submucosal tunneling resection (STER) was proposed ([Video 1]).
Multipolar traction pulley method combined with underwater endoscopic submucosal dissection for a large rectal laterally spreading tumor
Authors: Fabien Pinard, Jérémie Jacques, Thomas Grainville, Martin Bordet, Louis Jean Masgnaux, Mathieu Pioche, Timothée Wallenhorst
Journal: Endoscopy (2024)

Endoscopic submucosal dissection remains challenging, even with traction [1] to assist the procedure [2]. To overcome the decline in traction force as the dissection proceeds, an adaptive traction device, capable of being tightened to increase traction during the procedure, has shown interesting results [3]. Pulley methods have been described for early-stage gastric cancer [4]. However, since this first evaluation, no further study has been made in rectal and colonic locations.
Endoscopic submucosal dissection for diverticulum using combination of countertraction and circumferential-inversion method
Authors: Hiroshi Takayama, Yoshinori Morita, Toshitatsu Takao, Douglas Motomura, Madoka Takao, Takashi Toyonaga, Yuzo Kodama
Journal: Endoscopy (2024)

Endoscopic submucosal dissection (ESD) has been attempted in colorectal tumors involving diverticula, which lack a muscularis propria [1]. However, the R0 resection rate in tumors infiltrating the interior of the diverticulum remains low, and there is a risk of perforation [2] [3] [4]. We recently reported a novel traction method called the circumferential-inversion method, which inverts the lesion circumferentially [5]. Here, we describe the effectiveness of an innovative ESD approach combining countertraction and the circumferential-inversion method for a diverticulum-infiltrating tumor ([Video 1]).
Enhancing visualization with low echo reduction during endoscopic ultrasound-guided pancreatic duct drainage
Authors: Haruka Toyonaga, Tsuyoshi Hayashi, Masayo Motoya, Toshifumi Kin, Kuniyuki Takahashi, Akio Katanuma
Journal: Endoscopy (2024)

Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) is performed as an alternative when conventional endoscopic pancreatic duct drainage has failed [1]. Although accurately puncturing a narrow pancreatic duct remains challenging, contrast-enhanced EUS has been reported to be effective in puncturing poorly visible ducts [2] [3]. Low echo reduction (LER) mode, which is incorporated into a new EUS processor (EVIS EUS EU-ME3; Olympus, Tokyo, Japan), enhances visibility by suppressing low echo signals while maintaining high echo areas [4] [5]; this method may improve EUS-PD outcomes without using contrast media.
Endoscopic submucosal dissection for superficial esophageal cancer with ulcer scarring using a combination of pocket creation, gel immersion, and red dichromatic imaging
Authors: Tsubasa Ishikawa, Tomoaki Tashima, Takahiro Muramatsu, Yumi Mashimo, Shomei Ryozawa
Journal: Endoscopy (2024)

In recent years, the usefulness of endoscopic resection (ER) methods, such as underwater endoscopic submucosal dissection, has been widely reported [1]. Moreover, recently, from the viewpoint of securing the visual field during endoscopy, gel immersion endoscopy has been reported to be useful [2] [3]. Gel immersion endoscopy and underwater ER are used in challenging endoscopic procedures owing to their buoyancy effects. The pocket creation method is widely used to overcome endoscopic submucosal dissection (ESD) difficulties [4]. Red dichromatic imaging, which improves the visibility of deep blood vessels and bleeding points using longer wavelengths of light, is recently being extensively used, and its effectiveness has been reported [5]. We used red dichromatic imaging to improve visibility of the submucosal and muscular layers during ESD.
Endoscopic removal of esophageal foreign body embedded in muscularis propria
Authors: Jinhai Wang, Bin Qin, Lingzhi Qin, Haitao Shi, Xue Zhang, Peiqi Chen, Xin Liu
Journal: Endoscopy (2024)

A 53-year-old man presented with a 3-week history of retrosternal pain after the ingestion of hard food. A computed tomography (CT) scan of the chest indicated a transverse high-density opacity in the middle of the esophagus, extending into the right mediastinum. Esophagoscopy showed edema of the mucosa and granulation tissue at the right posterior esophageal wall 31 cm from the incisors, surface erosion with a small amount of purulent discharge, and no foreign body found in the lumen. Ultrasonography suggested a hyperechoic area in the right posterior muscularis propria layer of the esophagus, connected to a hypoechoic lesion outside the esophagus ([Fig. 1] a); imaging indicated an entirely embedded esophagus-penetrating foreign body and mediastinal abscess. A routine chest and enhanced CT scan revealed a high-density line, 22.9 mm in length, embedded in the middle esophagus and protruding into the mediastinum, with uneven soft tissue enhancement ([Fig. 1] b). No vascular injury was detected.
Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study
Authors: Leah E. Cahill, Rachel A. Warren, Allie S. Carew, Andrew P. Levy, John Sapp, Michelle Samuel, Elizabeth Selvin, Samantha K. Lavallée, Neil Poulter, Michel Marre, Stephen Harrap, Giuseppe Mancia, Katie Harris, John Chalmers, Mark Woodward, Eric B. Rimm
Journal: Diabetes Care (2024)

Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies.
Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC
Authors: Christine P. Limonte, Xiaoyu Gao, Ionut Bebu, Jesse C. Seegmiller, Amy B. Karger, Gayle M. Lorenzi, Mark Molitch, Harsha Karanchi, Bruce A. Perkins, Ian H. de Boer
Journal: Diabetes Care (2024)

Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D).
Surgical quality assessment for the prospective study of oncologic outcomes after laparoscopic modified complete mesocolic excision for nonmetastatic right colon cancer (PIONEER study)
Authors: Seung Yoon Yang, Min Jung Kim, Bong-Hyeon Kye, Yoon Dae Han, Min Soo Cho, Ji Won Park, Seung-Yong Jeong, Seung Ho Song, Jun Seok Park, Soo Yeun Park, Jin Kim, Byung Soh Min
Journal: International Journal of Surgery (2023)

Background: The modified complete mesocolic excision (mCME) procedure for right-sided colon cancer is a tailored approach based on the original complete mesocolic excision (CME) methodology. Limited studies evaluated the safety and feasibility of laparoscopic mCME using objective surgical quality assessments in patients with right colon cancer. The objectives of the PIONEER study were to evaluate oncologic outcomes after laparoscopic mCME and to identify optimal clinically relevant endpoints and values for standardizing laparoscopic right colon cancer surgery based on short-term outcomes of procedures performed by expert laparoscopic surgeons. Materials and methods: This is an ongoing prospective, multi-institutional, single-arm study conducted at five tertiary colorectal cancer centers in South Korea. Study registrants included 250 patients scheduled for laparoscopic mCME with right-sided colon adenocarcinoma (from the appendix to the proximal half of the transverse colon). The primary endpoint was 3-year disease-free survival. Secondary outcomes included 3-year overall survival, incidence of morbidity in the first 4 weeks postoperatively, completeness of mCME, central radicality, and distribution of metastatic lymph nodes. Survival data will be available after the final follow-up date (June 2024). Results: The postoperative complication rate was 12.9%, with a major complication rate of 2.7%. In 87% of patients, central radicality was achieved with dissection at or beyond the level of complete exposure of the superior mesenteric vein. Mesocolic plane resection with an intact mesocolon was achieved in 75.9% of patients, as assessed through photographs. Metastatic lymph node distribution varied by tumor location and extent. Seven optimal clinically relevant endpoints and values were identified based on the analysis of complications in low-risk patients. Conclusions: Laparoscopic mCME for right-sided colon cancer produced favorable short-term postoperative outcomes. The identified optimal clinically relevant endpoints and values can serve as a reference for evaluating surgical performance of this procedure.
‘Dumpling suture method’ versus traditional suture method of protective loop ileostomy in laparoscopic anterior rectal resection with specimen extraction through stoma incision: a retrospective comparative cohort study
Authors: Jiani Gu, Jin Wang, Xingwang Hu, Wenjun Ding, Long Cui, Peng Du, Zhonglin Liang, Tingyu Wu
Journal: International Journal of Surgery (2023)

Background: A diverting loop ileostomy (DLI) is performed in laparoscopic anterior rectal resection (LAR) surgery at high risk of anastomotic fistula. Minimally invasive surgery promotes postoperative recovery and cosmetics. To reduce abdominal trauma, specimen extraction through stoma incision (EXSI) is usually performed to avoid auxiliary abdominal incision with enlarged stomal incision. The traditional suture method (TSM) reduces the incision size by suturing the ends of the enlarged incision, leading to peristomal incisions and a higher risk of stomal complications. The study aimed to introduce the dumpling suture method (DSM) of PLI and compare this new method with TSM. Materials and Methods: The authors propose a novel stoma suture technique, which utilized a method of skin folding suture to reduce the enlarged incision size. A retrospective analysis was conducted on 71 consecutive patients with rectal cancer who underwent LAR-DLI with EXSI, and the intraoperative details and postoperative outcomes of the two groups were measured. Results: The DSM group showed a lower stomal complication rate (10.3 vs. 35.7%, P =0.016) than that of the TSM group. The scores of DET (Discoloration, Erosion, Tissue overgrowth), stomal pain, quality of life were all significantly lower in DSM group than in TSM group. In multivariate analysis, DSM was an independent protective factor for stoma-related complications. Operative time, time to first flatus, defecation and eat, nonstomal related postoperative complications were similar in both groups. Conclusion: DSM utilizes a method of skin folding suture to reduce the enlarged incision size, which is safe and effective in reducing the incidence of peristomal skin infections and stomal complications. This procedure offers a novel suturing approach for loop ileostomy with enlarged incision, effectively reducing the postoperative trauma and incidence of stomal complications.
Exhaled breath and urinary volatile organic compounds (VOCs) for cancer diagnoses, and microbial-related VOC metabolic pathway analysis: a systematic review and meta-analysis
Authors: Min Zhou, Qinghua Wang, Xinyi Lu, Ping Zhang, Rui Yang, Yu Chen, Jiazeng Xia, Daozhen Chen
Journal: International Journal of Surgery (2023)

Background: The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this study was to assess the diagnostic potential of exhaled breath and urinary VOCs in cancer detection. As VOCs are indicative of tumor and human metabolism, our work also sought to investigate the metabolic pathways linked to the development of cancerous tumors. Materials and Methods: An electronic search was performed in the PubMed database. Original studies on VOCs within exhaled breath and urine for cancer detection with a control group were included. A meta-analysis was conducted using a bivariate model to assess the sensitivity and specificity of the VOCs for cancer detection. Fagan’s nomogram was designed to leverage the findings from our diagnostic analysis for the purpose of estimating the likelihood of cancer in patients. Ultimately, MetOrigin was employed to conduct an analysis of the metabolic pathways associated with VOCs in relation to both human and/or microbiota. Results: The pooled sensitivity, specificity and the area under the curve for cancer screening utilizing exhaled breath and urinary VOCs were determined to be 0.89, 0.88, and 0.95, respectively. A pretest probability of 51% can be considered as the threshold for diagnosing cancers with VOCs. As the estimated pretest probability of cancer exceeds 51%, it becomes more appropriate to emphasize the ‘ruling in’ approach. Conversely, when the estimated pretest probability of cancer falls below 51%, it is more suitable to emphasize the ‘ruling out’ approach. A total of 14, 14, 6, and 7 microbiota-related VOCs were identified in relation to lung, colorectal, breast, and liver cancers, respectively. The enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in the aforementioned tumor types. Conclusions: The analysis of exhaled breath and urinary VOCs showed promise for cancer screening. In addition, the enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in four tumor types, namely lung, colorectum, breast and liver. These findings hold significant implications for the prospective clinical application of multiomics correlation in disease management and the exploration of potential therapeutic targets.