To investigate the implications of prophylactic intraoperative Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with D2 radical gastrectomy for locally advanced Gastric Cancer (AGC) in a randomized ...case control study.
Eighty consecutive patients with locally AGC were randomly separated into 2 groups: HIPEC group (Curative Resection + intraoperative HIPEC with cisplatin 50 mg/m
at 42.0 ± 1.0 °C for 60 min) and Control group (Curative Resection only). Intraoperative and post-operative events, clinical recovery, morbidity and the disease-free survival (DFS) rates were closely monitored.
Among the 40 HIPEC group patients, the highest intracranial temperature recorded during the procedure was 38.2 °C but the patient made an eventless recovery. Mild renal dysfunction, hyperbilirubinemia and mild liver dysfunction were recorded in the HIPEC group but their incidences were found to be statistically insignificant when compared with the control group (P > 0.05). The initial post-operative analysis revealed shorter post-operative stay for in the HIPEC group but further analysis revealed that it was related to the incidence of postoperative complication. During a median follow-up time of 41 months, there were 9/39 and 15/38 cases of disease progression in HIPEC and Control groups respectively, with a more favorable 3-year DFS (76.9% vs 60.5%) and a lower peritoneal recurrence rate (5% vs 30%) in the HIPEC group.
Prophylactic HIPEC with radical D2 Gastrectomy is safe and shows favorable survival and peritoneal recurrence rates for AGC with acceptable morbidity. Nevertheless, more structured multi-centered RCT should be carried out for more substantial evidence.
The lateral parabrachial nucleus (LPBN) is known to relay noxious information to the amygdala for processing affective responses. However, it is unclear whether the LPBN actively processes ...neuropathic pain characterized by persistent hyperalgesia with aversive emotional responses. Here we report that neuropathic pain-like hypersensitivity induced by common peroneal nerve (CPN) ligation increases nociceptive stimulation-induced responses in glutamatergic LPBN neurons. Optogenetic activation of GABAergic LPBN neurons does not affect basal nociception, but alleviates neuropathic pain-like behavior. Optogenetic activation of glutamatergic or inhibition of GABAergic LPBN neurons induces neuropathic pain-like behavior in naïve mice. Inhibition of glutamatergic LPBN neurons alleviates both basal nociception and neuropathic pain-like hypersensitivity. Repetitive pharmacogenetic activation of glutamatergic or GABAergic LPBN neurons respectively mimics or prevents the development of CPN ligation-induced neuropathic pain-like hypersensitivity. These findings indicate that a delicate balance between excitatory and inhibitory LPBN neuronal activity governs the development and maintenance of neuropathic pain.
Gastric cancer (GC) is one of the most malignant tumors and the second leading cause of cancer-related deaths in the world. Luteolin, a flavonoid present in many fruits and green plants, suppresses ...cancer progression. The effects of luteolin on GC cells and their underlying mechanisms remain unclear.
Effects of luteolin on cell proliferation, migration, invasion, and apoptosis were examined in vitro and in vivo by cell counting kit-8 (CCK-8), transwell assays, and flow cytometry, respectively. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blots were performed to evaluate Notch1 signaling and activation of epithelial-mesenchymal transition (EMT) in GC cells treated with or without luteolin. Immunohistochemistry was performed to examine proliferation and Notch1 expression in xenograft tumors.
Luteolin significantly inhibited cell proliferation, invasion, and migration in a dose-dependent and time-dependent manner and promoted cell apoptosis. Luteolin reversed EMT by shrinking the cytoskeleton and by inducing the expression of epithelial biomarker E-cadherin and downregulating the mesenchymal biomarkers N-cadherin, vimentin and Snail. Furthermore, Notch1 signaling was inhibited by luteolin, and downregulation of Notch1 had similar effects as luteolin treatment on cell proliferation, migration, and apoptosis. In addition, luteolin suppressed tumor growth in vivo. A higher expression of Notch1 correlated with a poor overall survival and a poor time to first progression. Furthermore, co-immunoprecipitation analysis revealed that activated Notch1 and β-catenin formed a complex and regulated cell proliferation, migration, and invasion.
In this study, GC progression was inhibited by luteolin through suppressing Notch1 signaling and reversing EMT, suggesting that luteolin may serve as an effective anti-tumor drug in GC treatment.
Gastric cancer (GC) remains one of the most common and malignant types of cancer due to its rapid progression, distant metastasis, and resistance to conventional chemotherapy, although efforts have ...been made to understand the underlying mechanism of this resistance and to improve clinical outcome. It is well recognized that tumor heterogeneity, a fundamental feature of malignancy, plays an essential role in the cancer development and chemoresistance. The model of tumor-initiating cell (TIC) has been proposed to explain the genetic, histological, and phenotypical heterogeneity of GC. TIC accounts for a minor subpopulation of tumor cells with key characteristics including high tumorigenicity, maintenance of self-renewal potential, giving rise to both tumorigenic and non-tumorigenic cancer cells, and resistance to chemotherapy. Regarding tumor-initiating cell of GC (GATIC), substantial studies have been performed to (1) identify the putative specific cell markers for purification and functional validation of GATICs; (2) trace the origin of GATICs; and (3) decode the regulatory mechanism of GATICs. Furthermore, recent studies demonstrate the plasticity of GATIC and the interaction between GATIC and its surrounding factors (TIC niche or tumor microenvironment). All these investigations pave the way for the development of GATIC-targeted therapy, which is in the phase of preclinical studies and clinical trials. Here, we interpret the heterogeneity of GC from the perspectives of TIC by reviewing the above-mentioned fundamental and clinical studies of GATICs. Problems encountered during the GATIC investigations and the potential solutions are also discussed.
Digital platforms have emerged as engines of innovation for companies to build complementary products and services in the ecosystems leveraged by the remarkable progress in digital technologies. ...However, the implementation of governance mechanisms to manage complementary innovation in digital platform ecosystems remains poorly understood. This study explores how digital platform owners implement governance mechanisms to manage complementary innovation along with the evolution of digital platforms. Based on the longitudinal case analysis of a leading Chinese digital platform in the Internet of Things sector, we identify four major governance mechanisms in digital platform ecosystems for managing complementors, which include agreement and rules, selective promotion, joint problem solving, and socialisation. We then develop two governance modes: the ‘commanding’ mode for mobilising complementors in the start‐up stage and the ‘enabling’ mode for locking in complementors in the scale‐up stage. This study reveals the major governance mechanisms and interaction dynamics between governance mechanisms and platform architecture in the evolution of digital platforms.
Dynamic electric field frequency actuated helical and spiral structures enable a plethora of attributes for advanced photonics and engineering in the contemporary era. Nevertheless, leveraging the ...frequency responsiveness of adaptive devices and systems within a broad dynamic range and maintaining restrained high-frequency induced heating remain challenging. Herein, we establish a frequency-actuated heliconical soft architecture that is quite distinct from that of common frequency-responsive soft materials. We achieve reversible modulation of the photonic bandgap in a wide spectral range by delicately coupling the frequency-dependent thermal effect, field-induced dielectric torque and elastic equilibrium. Furthermore, an information encoder prototype without the aid of complicated algorithm design is established to analogize an information encoding and decoding process with a more convenient and less costly way. A technique for taming and tailoring the distribution of the pitch length is exploited and embodied in a prototype of a spatially controlled soft photonic cavity and laser emission. This work demonstrates a distinct frequency responsiveness in a heliconical soft system, which may not merely inspire the interest in field-assisted bottom-up molecular engineering of soft matter but also facilitate the practicality of adaptive photonics.
Even though treatment modalities such as adjuvant systemic radio-chemotherapy and neoadjuvant chemotherapy (NAC) have individually have improved overall survival (OS) and progression-free survival ...(PFS) rates in advanced Gastric Cancer (AGC), the peritoneum still presides as a common site of treatment failure and disease recurrence. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) has been acknowledged as prophylaxis for peritoneal carcinomatosis (PC) in AGC patients and in this study, we aim at investigating the safety and efficacy of the combination of neoadjuvant laparoscopic HIPEC (NLHIPEC) with NAC in the neoadjuvant phase followed by surgery of curative intent with intraoperative HIPEC followed by adjuvant chemotherapy (AC).
In this multicenter Phase III randomized controlled trial, 326 patients will be randomly separated into 2 groups into a 1:1 ratio after laparoscopic exploration. The experiment arm will receive the proposed comprehensive Dragon II regimen while the control group will undergo standard R0 D2 followed by 8 cycles of AC with oxaliplatin with S-1 (SOX) regimen. The Dragon II regimen comprises of 1 cycle of NLHIPEC for 60mins at 43 ± 0.5 °C with 80 mg/m
of Paclitaxel followed by 3 cycles of NAC with SOX regimen and after assessment, standard R0 D2 gastrectomy with intraoperative HIPEC followed by 5 cycles of SOX regimen chemotherapy. The end-points for the study are 5 year PFS, 5 year OS, peritoneal metastasis rate (PMR) and morbidity rate.
This study is one of the first to combine NLHIPEC with NAC in the preoperative phase which is speculated to provide local management of occult peritoneal carcinomatosis or peritoneal free cancer cells while NAC will promote tumor downsizing and down-staging. The addition of the intraoperative HIPEC is speculated to manage dissemination due to surgical trauma. Where the roles of intraoperative HIPEC and NAC have individually been investigated, this study provides innovative insight on a more comprehensive approach to management of AGC at high risk of peritoneal recurrence. It is expected that the combination of NLHIPEC with NAC and HIPEC will increase PFS by 15% and decrease PMR after gastrectomy of curative intent.
World Health Organization Clinical Trials - International Registry Platform (WHO-ICTRP) with Registration ID ChiCTR1900024552, Registered Prospectively on the 16th July, 2019.
Long noncoding RNA UCA1 has emerged as a novel regulator in cancer initiation and progression of various cancers. However, function and underlying mechanism of UCA1 in the progression of gastric ...cancer (GC) remain unclear. In the present study, we report that UCA1 expressed highly in GC tissues and GC cells, which was partly induced by SP1. UCA1 promoted GC cell proliferation and G1/S transition in vitro and in vivo. Moreover, UCA1 exerted its function through interacting with EZH2, promoting direct interaction with cyclin D1 promoter to activate the translation of cyclin D1. Furthermore, AKT/GSK-3B/cyclin D1 axis was activated to upregulate cyclin D1 due to overexpression of UCA1. In addition, EZH2 and phosphorylated AKT induced by UCA1 could impact each other to form a positive feedback to promote cyclin D1 expression. This study demonstrated that UCA1 as a critical regulator involved in GC proliferation and cell cycle progression by promoting cyclin D1 expression, which indicates that it may be clinically a potential therapeutic target in GC.
Biglycan (BGN) is an important component of the extracellular matrix (ECM) that is implicated in a variety of human cancers. In our previous study, we reported that BGN was overexpressed in gastric ...cancer (GC) tissues and promoted cancer metastasis. Moreover, the tubular formation capacity in HUVECs was promoted by stimulation with culture media from BGN-overexpressing GC cells, but the exact underlying mechanism is still unknown. The purpose of this study was to determine the role and molecular mechanism of BGN in VEGF expression in endothelial cells. We found that BGN stimulation of endothelial cells increased the interaction between NF-kB and the HIF-1α promoter, leading to enhanced promoter activity and increased HIF-1α mRNA levels, as well as augmented HIF-1 activity that resulted in VEGF expression. All of this was dependent on the interaction of BGN with its receptors, TLR2 and TLR4. Moreover, we found that BGN enhanced endothelial cell migration and proliferation, as well as tube formation, in a TLR signaling pathway-dependent manner. In addition, endothelial cell-derived VEGF in turn was found to act on GC cells and promotes their migration. The combined findings of our current and previous studies suggest that BGN secreted from GC cells into the tumor stroma promotes GC development, as well as its progression, potentially through the chronic activation of tumor angiogenesis.
•BGN is member of SLRPs, which is found in a variety of human cancers.•BGN stimulation of endothelial cells increased the expression of VEGF through NF-kB and the HIF-1α.•BGN enhanced endothelial cell migration, proliferation and tube formation in a TLR signaling pathway-dependent manner.•Endothelial cell-derived VEGF in turn acts on GC cells and promotes the migration of GC cells.
We performed this study to better assess the relationship between serotonin transporter (SERT) insertion/deletion polymorphism and the risk of irritable bowel syndrome (IBS).
Eligible studies were ...searched in PubMed, Medline, Embase and CNKI. A total of 27 studies with 7039 participants were analyzed.
Significant association with the risk of IBS was detected for the SERT insertion/deletion polymorphism in additive comparison (p < 0.0001). Further subgroup analyses according to ethnicity of participants revealed that the SERT insertion/deletion polymorphism was significantly associated with the risk of IBS in Asians (dominant model: p = 0.001; recessive model: p = 0.0003; allele model: p = 0.001) and Caucasians (dominant model: p = 0.04; additive model: p < 0.0001). When we stratified available data according to type of disease, we found that the SERT insertion/deletion polymorphism was significantly correlated with the risk of constipation predominant IBS (IBS-C) in recessive comparison (p = 0.04). However, no positive results were detected in the diarrhea predominant IBS (IBS-D) and mixture of diarrhea and constipation IBS (IBS-M) subgroups.
Our findings indicated that the SERT insertion/deletion polymorphism may serve as a genetic biomarker of IBS in Asians and Caucasians.
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