Th localized resected tumors and a 19 months median survival in patien…

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작성자 Syreeta 댓글 0건 조회 6회 작성일 23-10-04 18:38

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Th localized resected tumors and a 19 months median survival in patients with metastatic disease [6]. Patients with PACC frequently present with abdominal pain and bloating as the dominant symptoms, and in some cases their initial clinical diagnosis given was acute pancreatitis [1, 7, 8]. Elevation of serum lipase levels can be associated with systemic fat necrosis, a significant cause of morbidities in PACC patients [9?2]. However, elevated serum lipase and amylase levels can be seen in both PACC and acute pancreatitis leading to difficulties in establishing a correct diagnosis [13, 14]. Reliable markers of PACC have been slowly emerging such as carcinoembryonic antigen (CEA) [15], cytokeratin 18 (CK18) [16] and B-cell lymphoma/leukemia 10 (BCL10) [17, 18] allowing us to distinguish acinar cell carcinoma from normal acinar cells or other pancreatic cancers through histology. The genetic and molecular abnormalities that lead to PACC have not been fully identified. Recent studies have found that genes regulating DNA repair may be mutated in PACC patients. DNA repair mutations were noted in 45 of PACC tumors, BRCA2 being the most common gene, followed by BRCA1 and ATM20 [3, 6, 19]. Previously, we reported on a case of a PACC patient receiving personally designed treatments based on the genetic and molecular profiles of his tumor [20]. We cultured the patient's tumor biopsies into primary cell lines and treated them with different chemotherapy agents [20]. The outcome was that a DNA replication inhibitor, (irinotecan), a DNA intercalating agent and transcription inhibitor (doxorubicin), and a tyrosine kinase inhibitor (imatinib) were among the most effective agents against his tumor cells in cell culture [20]. As a result of the observations seen in vitro, liposomal doxorubicin was administered and the patient had evidence of a sustained clinical response throughout the treatment regimen [20].Here, we report the characterization of a PACC patient derived tumor xenograft (PDTX) mouse model (PA-018) from the patient's tumor biopsy. With the use of PA-018, multiple chemotherapies (5-FU, oxaliplatin, gemcitabine, liposomal doxorubicin) and targeted agents (irinotecan, bevacizumab, erlotinib, imatinib) were tested in vivo. Of the therapies tested, oxaliplatin was the most promising and demonstrated sustained antitumor activity after only 3 weekly treatments. Therefore, evaluation of potential effective treatments using this PDTX model is a viable technology that may facilitate the discovery of effective treatments against thiCapivasertibCapivasertib Abstract(s)">PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16989806 available to the PACC scientific community.MethodsDevelopment of PDTX modelBiopsy tissue from PACC liver metastasis was implanted subcutaneously into two 5 week old anesthetized athymic nude female mice strain #069 (Harlan Laboratories, Indianapolis, IN) under IACUC approved procedures. Implanted tumors were harvested and frozen as 5 mm3 fragments in 10 DMSO-DMEM media and multiple "passages" were continued in athymic nude mice. Applying this technique to the patient's tumor has created a renewable source of PACC tissue and a representative in vivo model to test promising drugs. This PACC PDTX model is available at Charles Rivers (CR) Discovery Services (Morrisville, NC).In vivo implantation and tumor growthFor the in vivo study, 6 week old female athymic nude mice strain #490 (CR Discovery Services) were subcutaneously implanted with 5 mm3 tum.

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