Maor Lahav's research while affiliated with Sheba Medical Center and other places

Publications (22)

Article
Background: Syndecan-1 (SDC1) has multiple functions in tumorigenesis in general, and specifically in pancreatic cancer. We aimed to evaluate SDC1 as a diagnostic and prognostic biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: In this case-control study, patients newly diagnosed with a biopsy-proven PDAC were enrolled...
Article
Background and aims: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) or biopsy is widely practiced. Optimal sonographic visualization of the needle is critical for image guided interventions. There are several commercially available needles but no bench-top testing and direct comparison of these needles to reveal their inherent ech...
Article
Full-text available
The miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC). An open-label Phase 1/2a study in the first-line setting of patients...
Article
270 Background: K-Ras mutation G12D is most prevalent in pancreatic adenocarcinoma (PDAC). siRNA against the K-RasG12D(siG12D) mutant had showed significant preclinical anti-tumor effects. siG12D LODER - is a miniature biodegradable polymeric matrix that encompasses anti K-RasG12D siRNA drug, designed to release the drug regionally along 4 months....
Article
Full-text available
Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged...
Article
Full-text available
4037 Background:K-Ras mutation G12D is most prevalent in pancreatic adenocarcinoma (PDAC). siRNA against the K-Ras G12D (siG12D) mutant had showed significant preclinical anti-tumor effects. siG12D LODER - miniature biodegradable polymeric matrix that encompasses anti-K-RasG12D siRNA drug, is placed with Endoscopic US biopsy and designed to continu...
Article
Double balloon enteroscopy is a new technique that enables deep intubation of the endoscope into the small bowel lumen. Through a channel in the endoscope, invasive procedures such as biopsy, polypectomy and hemostasis can be performed, avoiding the need for surgery. To prospectively analyze our results of the first 124 DBEs performed since Februar...
Article
Inducible heat shock proteins (iHsp), Hsp25/27 and Hsp70, play essential roles in protecting cells against stress and, in intestinal mucosal inflammation, potentially lessening the extent and severity of injury. We examined the expression and regulation of iHsp in human and experimental inflammatory bowel diseases (IBD) and in vitro. iHsp expressio...
Article
Cystic lesions of the pancreas are detected more often nowadays. Many are considered premalignant and pancreatic resection is recommended. This study was undertaken to assess the natural course of asymptomatic pancreatic cysts and their malignant potential. All patients referred for endoscopic ultrasound (EUS) between 1994 and 2003 because of pancr...
Article
Video capsule endoscopy (VCE) enables visualization of the entire small bowel and can identify lesions that may go undetected by conventional endoscopy and radiography. In this study, we assessed whether patient's selection based on symptoms may increase the yield of VCE in the diagnosis of Crohn's disease (CD). Findings of 125 consecutive patients...
Article
Allicin, the active substance of fresh crushed garlic has different biological activities and was implicated as an anti-inflammatory agent. Epithelial cells have an important role in intestinal inflammation. The aim of this study was to assess the immunomodulatory effect of allicin on intestinal epithelial cells. The spontaneous and TNF-alpha-stimu...
Article
Crohn's disease (CD) is a chronic transmural inflammatory disease of unknown etiology. Genetic background may influence the nature of disease. The Jewish population in Israel is composed of Ashkenazi and Sephardic Jews, who differ in their genetic background. Previous studies have reported that the prevalence of CD in Sephardic Jews is lower than i...
Article
Diarrhea is a common sequela of deregulated immune pathways underlying the wide range of intestinal acute and chronic diseases. The ongoing investigation of novel immune components and susceptibility factors allows better understanding of these pathologic mechanisms and continues to advance therapeutic options.
Article
Lidocaine and related local anaesthetics have been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms underlying their therapeutic effect are poorly defined. Intestinal epithelial cells play an important role in the mucosal inflammatory response that leads to tissue damage in UC via the secretion of pro-infla...
Article
Full-text available
Intestinal epithelial cells secrete proinflammatory cytokines and chemokines that are crucial in mucosal defense. However, this secretion must be tightly regulated, because uncontrolled secretion of proinflammatory mediators may lead to chronic inflammation and mucosal damage. The aim of this study was to determine whether somatostatin, secreted wi...
Article
Intestinal epithelial cells secrete proinflammatory cytokines and chemokines that are crucial in mucosal defense. However, this secretion must be tightly regulated, because uncontrolled secretion of proinflammatory mediators may lead to chronic inflammation and mucosal damage, The aim of this study was to determine whether somatostatin, secreted wi...

Citations

... A phase I clinical trial (NCT01188785) demonstrated that siG12D LODER is well tolerated, safe and has potential efficacy against pancreatic ductal adenocarcinomas [95]. In addition, a phase II (NCT01676259) continues to evaluate the efficacy of siG12D LODER in combination with chemotherapy. ...
... In vitro, preclinical data demonstrate reliable anti-neoplastic effects of mutant specific K-ras siRNA in pancreatic cancer cell lines [14]. Presented below are the promising early clinical results of a study using an innovative loco-regional delivery method of a siRNA targeting the mutated K-RAS oncogene [15]. ...
... Proinflammatory cytokines, such as TNF-α and IFN-γ, can lead to the destruction of TJ protein structure and a decrease in TJ protein expression by activating the NF-κB/MLCK signaling pathway [9,43]. Previous studies showed that SST could inhibit the inflammatory response of intestinal mucosa and IECs [44,45] and inhibit the activation of TLR4/NF-κB signaling [20]. TLR signaling plays an essential role in I/RIinduced intestinal mucosa inflammation and IEB dysfunction, and MyD88 acts as a universal adaptor protein involved in TLRinduced NF-κB activation [28,29]. ...
... New nitinol-based needles have been developed with enhanced flexibility to improve the technical success of transduodenal sampling [18][19][20]. Nevertheless, a recent RCT comparing a flexible 19 G vs. a standard 22 G needle in pancreatic head lesions failed to show any advantage of using the larger needle at intention-to-treat analysis (diagnostic accuracy for malignancy 69.5 % vs 87.3 %, respectively; P = 0.02). ...
... Stimulation of mAChR has reduced this TNF-a-induced activation of NF-jB signaling pathway (Fig. 4C). In addition, the increases in NF-jB transcription activity and in IL-8 production, both of which have been shown to be typical phenomena subsequent to cytokine stimulation including TNF-a[40][41][42][43], were suppressed by the precedent stimulation of mAChR (Fig. 5). These results have suggested that mAChR counter the cytokine-induced propagation of colitis by suppressing TNF-a signaling, including NF-jB activation and IL-8 production. ...
... siG12D-LODERTM aims to provide a local drug with prolonged activity within the tumor while ensuring that the siRNA drug is protected from degradation. It has shown its potential in phase I trial of combined chemotherapy in 12 patients with PDAC [93]. ...
... The KRAS-targeted siRNA-polymeric nanoparticles for local therapy, siG12D-LODER, were designed by Silenseed Ltd. for patients with locally advanced pancreatic cancer. The biodegradable polymer matrix, Local Drug EluteR (LODER), was used to release the G12D-mutated KRAS-targeted siRNA locally within a pancreatic tumor microenvironment for controlled and prolonged delivery [65]. The LODER matrix consists of a copolymer of poly lactic-co-glycolic acid (PLGA) of a high molecular weight greater than 50 kD. ...
... These findings are similar with those of other studies. 4,8,9,11,12 Regarding the endoscopic findings and diagnoses with DBE, the commonest finding was ulcerations or erosions (40.3%) which were due to tuberculosis (36.9%) and Crohn's disease (30.4%) and others. Ulcerating lesions were also common in Korean study 9 but in Western study 8,13 angiodysplasia was the most common finding. ...
... SST binds to the β-cells of the pancreas to inhibit voltage-gated calcium channels, resulting in the suppression of the early insulin response to glucose and, thus, downmodulating the storage of energy in adipose tissue [29]. SST suppresses several immune functions, such as lymphocyte proliferation, immunoglobulin production, and the release of proinflammatory cytokines such as interferonγ (IFNγ) and interleukin-8 (IL-8) [30,31]. The effect of SST under physiological conditions is partially determined by the types of SSTRs expressed on the tissue's surface [8]. ...
... The modulating effects of LA on the immune system have been widely described [14,24], and different mechanisms of action have been proposed [14,[25][26][27][28][29][30][31][32][33][34][35][36]: leucocyte inhibition, decrease in synthesis and release of inflammatory mediators, and decrease in vascular hyperpermeability and edema formation ( Table 4). ...