Author: Falato, Armando ; Bianco, Francesco ; Frago, Ricardo ; De Franciscis, Silvia ; Biondo, Sebastiano ; Kreisler, Esther ; Trenti, Loris ; Alberti, Piero A ; Blanco, Ana ; Solis, Alejandro ; Espin, Eloy ; Galvez, Ana ; Golda, Thomas ; Fraccalvieri, Domenico ; Miguel, Bernat ; Verdaguer, Mireia ; Barrios, Oriana

IMPORTANCEIn patients operated on for low rectal cancer, 2-stage Turnbull-Cutait pull-through hand-sewn coloanal anastomosis provides benefits in terms of postoperative morbidity compared with standard hand-sewn coloanal anastomosis associated with diverting ileostomy and further ileostomy reversal.OBJECTIVETo compare long-term results of these 2 techniques after ultralow rectal resection for rectal cancer.DESIGN, Setting, and ParticipantsIn this randomized multicenter clinical trial, neither patients nor surgeons were blinded for technique. Patients were recruited in 3 centers. Patients undergoing ultralow anterior rectal resection needing hand-sewn coloanal anastomosis were randomly assigned to 2-stage Turnbull-Cutait pull-through hand-sewn coloanal anastomosis (n = 46) or standard hand-sewn coloanal anastomosis associated with diverting ileostomy (n = 46).INTERVENTIONSAll patients underwent ultralow anterior resection. Patients assigned to the 2-stage Turnbull-Cutait pull-through group underwent exteriorization of a segment of left colon through the anal canal. After 6 to 10 days, the exteriorized colon was resected and a delayed hand-sewn coloanal anastomosis performed. For patients assigned to standard coloanal anastomosis, the hand-sewn coloanal anastomosis was performed with diverting ileostomy during the first operation. Ileostomy closure was scheduled after adjuvant treatment was completed in about 6 to 8 months.MAIN OUTCOME AND MEASUREThe study aimed to compare the differences between the 2 groups in terms of long-term surgery-related morbidity, functional, and oncological outcomes at 3 years postoperatively. Data were analyzed from October 1, 2018, through October 31, 2021.RESULTSThe 92 patients randomized in the first study were included for the 3-year follow-up. The overall morbidity rate in the 2 groups showed that 15 patients (16.3%) had complications with a difference of 6.52 (95% CI, −8.93 to 21.79). Nine patients (19.6%) and 6 patients (13.0%) in the 2-stage Turnbull-Cutait pull-through group and hand-sewn coloanal anastomosis group, respectively, had complications without statistically significant differences (P = .57). Oncological results were comparable between the groups. Long-term fecal continence in the CCA and TCA groups, respectively, assessed using the Wexner Incontinence Score was 10.9 (5.50-15.5) vs 13.0 (7.25-16.0; P = .92), Low Anterior Resection Syndrome score was 32.0 (21.0-37.0) vs 34.0 (23.2-38.5; P = .76), and Colorectal Functional Outcome score was 38.5 (23.0-47.1) vs 40.8 (23.3-58.2; P = .30).CONCLUSIONS AND RELEVANCEIn this study, after a 3-year follow-up period, 2-stage Turnbull-Cutait anastomosis for ultralow rectal cancer could be considered as a surgical alternative that has the valuable benefit of avoiding a temporary stoma with similar results in terms of morbidity, fecal continence, patient satisfaction, quality of life, and oncological outcomes when compared with hand-sewn coloanal anastomosis with ileostomy.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01766661

01 Sep 2024·Phytomedicine

Exploring the potential of cryptochlorogenic acid as a dietary adjuvant for multi-target combined lung cancer treatment

Article

Author: Guo, Shuai ; Liu, Yinuo ; Cao, Yuchen ; Chen, Yue ; Ma, Zhouye ; Bai, Xue

BACKGROUNDLung cancer is a highly malignant disease with limited treatment options and significant adverse effects. It is urgent to develop novel treatment strategies for lung cancer. In recent years, TMEM16A has been confirmed as a specific drug target for lung cancer. The development of TMEM16A-targeting drugs and combined administration for the treatment of lung cancer has become a research hotspot.METHODSFluorescence screening and electrophysiological experiments were conducted to confirm the inhibitory effect of CCA on TMEM16A. Molecular dynamics simulation and site-directed mutagenesis were employed to analyze the binding mode of CCA and TMEM16A. CCK-8, colony formation, wound healing, transwell, and annexin-V experiments were conducted to explore the regulatory effects and mechanisms of CCA on the proliferation, migration, and apoptosis of lung cancer cells. Tumor model mice and pharmacokinetic experiments were used to examine the efficacy and safety of CCA and cisplatin in vivo.RESULTSThis study firstly confirmed that CCA effectively inhibits TMEM16A to exert anticancer effects and analyzed the pharmacological mechanism. CCA bound to S517/N546/E623/E633/Q637 of TMEM16A through hydrogen bonding and electrostatic interactions. It inhibited the proliferation and migration, and induced apoptosis of lung cancer cells by targeting TMEM16A. In addition, the combined administration of CCA and cisplatin exhibited a synergistic effect, enhancing the efficacy of lung cancer treatment while reducing side effects.CONCLUSIONCCA is an effective novel inhibitor of TMEM16A, and it synergizes with cisplatin in anticancer treatment. These findings will provide new research ideas and lead compound for the combination therapy of lung cancer.

01 Jun 2024·Journal of Gastrointestinal Oncology

Promotion of perineural invasion of cholangiocarcinoma by Schwann cells via nerve growth factor

Article

Author: Qian, Xingwang ; Zhang, Chong ; Feng, Ruo ; Wang, Fazhan ; Zhai, Wenlong ; Liu, Enchi ; Qin, Zhihai ; Tran, Nguyen

BackgroundCholangiocarcinoma (CCA), a highly lethal tumor of the hepatobiliary system originating from bile duct epithelium, can be divided into the intrahepatic, hilar, and extrahepatic types. Due to its insidious onset and atypical early clinical symptoms, the overall prognosis is poor. One of the important factors contributing to the poor prognosis of CCA is the occurrence of perineural invasion (PNI), but the specific mechanisms regarding how it contributes to the occurrence of PNI are still unclear. The main purpose of this study is to explore the molecular mechanism leading to the occurrence of PNI and provide new ideas for clinical treatment.MethodsCCA cell lines and Schwann cells (SCs) were stimulated to observe the changes in cell behavior. SCs cocultured with tumor supernatant and SCs cultured in normal medium were subjected to transcriptome sequencing to screen the significantly upregulated genes. Following this, the two types of tumor cells were cultured with SC supernatant, and the changes in behavior of the tumor cells were observed. Nonobese diabetic-severe combined immunodeficiency disease (NOD-SCID) mice were injected with cell suspension supplemented with nerve growth factor (NGF) via the sciatic nerve. Four weeks later, the mice were euthanized and the tumor sections were removed and stained.ResultsNerve invasion by tumor cells was common in CCA tissues. SCs were observed in tumor tissues, and the number of SCs in tumor tissues and the degree of PNI were much higher than were those in normal tissues or tissues without PNI. The overall survival time was shorter in patients with CCA with PNI than in patients without PNI. SCs were enriched in CCA tissues, indicating the presence of PNI and associated with poor prognosis in CCA patients. CCA was found to promote NGF secretion from SCs in vitro. After the addition of exogenous NGF in CCA cell culture medium, the proliferation activity and migration ability of CCA cells were significantly increased, suggesting that SCs can promote the proliferation and migration of CCA through the secretion of NGF. NGF, in turn, was observed to promote epithelial-mesenchymal transition in CCA through tropomyosin receptor kinase A (TrkA), thus promoting its progression. Tumor growth in mice shows that NGF can promote PNI in CCA.ConclusionsIn CCA, tumor cells can promote the secretion of NGF by SCs, which promotes the progression of CCA and PNI by binding to its high-affinity receptor TrkA, leading to poor prognosis.

100 Deals associated with Lobenzarit Sodium

External Link

KEGG	Wiki	ATC	Drug Bank
D01808	Lobenzarit Sodium	M01C	-

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Rheumatoid Arthritis	JP	Chugai Pharmaceutical Co., Ltd.	01 Jan 1986

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Lobenzarit Sodium

Overview

Basic Info

Structure

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation