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"Lahat, Golan"
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The political implications of Kant's theory of knowledge : rethinking progress
\"Immanuel Kant has long been considered one of the leading exponents of the theory of knowledge with his philosophical writings inspiring generations of political theorists, underpinning many notions and ideas on the concept of progress. Based on and innovative reading of Kant's theory of knowledge, this book challenges contemporary critiques of the concept of progress from post-Marxist, post-Modern and or existentialist approaches which dismiss progress as an anachronistic and deceptive concept that has formed the basis of many of modernity's abominations. Instead this book reveals Kant's unique synthetic theory of knowledge, arguing that the idea of progress should be thought of as a crucial political idea in matters of political management at the outset of the 21st century\"-- Provided by publisher.
Book
Increased Rate of Complete Pathologic Response After Neoadjuvant FOLFIRINOX for BRCA Mutation Carriers with Borderline Resectable Pancreatic Cancer
BackgroundNeoadjuvant FOLFIRINOX is a standard-of-care treatment for BRPC patients. Patients with gBRCAm who have demonstrated improved response to platinum-based chemotherapy may have impaired homologous repair deficiency. This study aimed to describe the pathologic complete response rate and long-term survival for patients with germline BRCA1 or BRCA2 mutation (gBRCAm) and borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX.MethodsA dual-center retrospective analysis was performed. Patients who had BRPC treated with neoadjuvant FOLFIRINOX followed by curative resection were identified from clinical databases. Pathologic complete response was defined as no viable tumor cells present in the specimen. Common founder Jewish germline BRCA1 or BRCA2 mutation was determined for available patients.ResultsThe 61 BRPC patients in this study underwent resection after neoadjuvant FOLFIRINOX. Analysis of BRCA mutation was performed for 39 patients, and 9 patients were found to be BRCA2 germline mutation carriers. The pathologic complete response rate was 44.4% for the gBRCAm patients and 10% for the BRCA non-carriers (p = 0.009). The median disease-free survival was not reached for the gBRCAm patients and was 7 months for the BRCA non-carriers (p = 0.03). The median overall survival was not reached for the gBRCAm patients and was 32 months for the BRCA non-carriers (p = 0.2). After a mean follow-up period of 33.7 months, all eight patients with pathologic complete response were disease-free.ConclusionsThe study showed that gBRCAm patients with BRPC have an increased chance for pathologic complete response and prolonged survival after neoadjuvant FOLFIRINOX. The results support the benefit of exposing gBRCAm patients to platinum-based chemotherapy early in the course of the disease. Neoadjuvant FOLFIRINOX should be considered for BRCA carriers who have resectable pancreatic cancer.
Journal Article
Porto-Rex Shunt for Left Portal Vein Reconstruction During Right Extended Hepatectomy for Advanced Extrahepatic Biliary Cancer
Resection offers the only chance of long-term survival or cure for perihilar cancer, provided R0 resection is achieved with margin-negative status of the remnant liver, bile duct, proximal hepatic artery, and portal vein. End-to-end anastomosis of the portal trunk to the left portal branch is the conventional portal reconstruction in cases of right extended hepatectomy requiring resection of the portal vein bifurcation. This mandatory reconstruction may be challenging due to (1) vessel incongruence, (2) fragility of the left portal branch wall, and more importantly, and (3) the divergent orientation of the two vessels exposing to vascular twisting/kinking. We report here the first two cases of porto-Rex shunt, between the portal vein trunk and the left portal vein in the umbilical fissure during right extended hepatectomy for advanced extrahepatic biliary cancer: one following failed conventional portal reconstruction and one to achieve macroscopically complete resection.
Journal Article
Ex vivo organotypic cultures for synergistic therapy prioritization identify patient-specific responses to combined MEK and Src inhibition in colorectal cancer
Translating preclinical studies to effective treatment protocols and identifying specific therapeutic responses in individuals with cancer is challenging. This may arise due to the complex genetic makeup of tumor cells and the impact of their multifaceted tumor microenvironment on drug response. To find new clinically relevant drug combinations for colorectal cancer (CRC), we prioritized the top five synergistic combinations from a large in vitro screen for ex vivo testing on 29 freshly resected human CRC tumors and found that only the combination of mitogen-activated protein kinase kinase (MEK) and proto-oncogene tyrosine-protein kinase Src (Src) inhibition was effective when tested ex vivo. Pretreatment phosphorylated Src (pSrc) was identified as a predictive biomarker for MEK and Src inhibition only in the absence of KRAS
mutations. Overall, we demonstrate the potential of using ex vivo platforms to identify drug combinations and discover MEK and Src dual inhibition as an effective drug combination in a predefined subset of individuals with CRC.
Journal Article