The poor prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is due in part to the highly fibrotic nature of the tumors that impedes delivery of therapeutics, including nanoparticles ...(NPs). Our prior studies demonstrated that proglumide, a cholecystokinin receptor (CCKR) antagonist, reduced fibrosis pervading PanIN lesions in mice. Here, we further detail how the reduced fibrosis elicited by proglumide achieves the normalization of the desmoplastic tumor microenvironment (TME) and improves nanoparticle uptake. One week following the orthotopic injection of PDAC cells, mice were randomized to normal or proglumide-treated water for 3-6 weeks. Tumors were analyzed ex vivo for fibrosis, vascularity, stellate cell activation, vascular patency, and nanoparticle distribution. The histological staining and three-dimensional imaging of tumors each indicated a reduction in stromal collagen in proglumide-treated mice. Proglumide treatment increased tumor vascularity and decreased the activation of cancer-associated fibroblasts (CAFs). Additionally, PANC-1 cells with the shRNA-mediated knockdown of the CCK2 receptor showed an even greater reduction in collagen, indicating the CCK2 receptors on tumor cells contribute to the desmoplastic TME. Proglumide-mediated reduction in fibrosis also led to functional changes in the TME as evidenced by the enhanced intra-tumoral distribution of small (<12 nm) Rhodamine-loaded nanoparticles. The documented in vivo, tumor cell-intrinsic anti-fibrotic effects of CCK2R blockade in both an immunocompetent syngeneic murine PDAC model as well as a human PDAC xenograft model demonstrates that CCK2R antagonists, such as proglumide, can improve the delivery of nano-encapsulated therapeutics or imaging agents to pancreatic tumors.
Over the course of medical school, students’ optimism and hopefulness often devolve into a cynical view of medicine that continues throughout clinical rotations and beyond (Neumann et al., Acad Med ...86(8):996–1009,
2011
). Here, we present a qualitative evaluation of a novel immersive elective in pediatric psycho-oncology coupled with narrative medicine and its impact on students. Participants were third- and fourth-year medical students who were relieved of traditional clinical duties. Alternatively, they shadowed pediatric cancer patients, keeping narrative journals of their observations and insights. A trained team of pre-clinical medical students and faculty conducted a retrospective analysis of 120 journals written between 2008 and 2019. They compared recurring concepts to assess how blending experiential learning and reflective writing influenced the attitudes and behaviors of students. Consistent themes emerged related to developing a rich understanding of patient experiences, a humanistic appreciation of the context of illness, the ability to meaningfully reflect on insights to critically ill children, and an appreciation for the unique learning opportunity. Additionally, families expressed gratitude for the students’ attentiveness to their emotional needs. By the conclusion of the elective, most students discovered that they had reignited their intrinsic empathic behaviors and were provided with beneficial insights that they believed would continue into future rotations. Experiential teaching methods paired with narrative reflection may be a valuable and therapeutic tool to learn the intricacies of the patient perspective, with the potential to enhance humanism in students during a critical time in their medical training when empathy tends to drift. Longitudinal and quantitative studies are warranted to better understand the degree and duration of specific benefits.
Amyloidosis with renal involvement is a well-known cause of nephrotic syndrome. Immunoglobulin light-chain amyloidosis (AL), which is a result of monoclonal light-chain deposition in the kidney from ...plasma cell dyscrasia, is rare before the age of 40 and typically occurs in old patients. Most cases of renal amyloidosis in young patients are secondary to chronic inflammatory disease. We are reporting a case of a 37-year-old male who was transferred to our hospital for evaluation of possibly acquired bleeding disorder. He was initially presented to an outside hospital with bleeding per rectum for three days duration and one-week history of abdominal pain and bloating. He was found to have nephrotic range proteinuria with hypoalbuminemia and hyperlipidemia. A kidney biopsy was performed to identify the cause of his nephrotic syndrome, and a biopsy showed AL amyloidosis. Bone marrow biopsy performed showed plasma cell myeloma, and the patient was started on induction chemotherapy. Even though the incidence of AL amyloidosis is low before age of 40, we should always perform monoclonal gammopathy workup in patients with nephrotic syndrome regardless of the age. Prompt bone marrow biopsy should be performed to confirm the diagnosis, and starting the treatment as one of the factors that affect the prognosis of AL amyloidosis is early diagnosis.
Amyloidosis with renal involvement is a well-known cause of nephrotic syndrome. Immunoglobulin light-chain amyloidosis (AL), which is a result of monoclonal light-chain deposition in the kidney from ...plasma cell dyscrasia, is rare before the age of 40 and typically occurs in old patients. Most cases of renal amyloidosis in young patients are secondary to chronic inflammatory disease. We are reporting a case of a 37-year-old male who was transferred to our hospital for evaluation of possibly acquired bleeding disorder. He was initially presented to an outside hospital with bleeding per rectum for three days duration and one-week history of abdominal pain and bloating. He was found to have nephrotic range proteinuria with hypoalbuminemia and hyperlipidemia. A kidney biopsy was performed to identify the cause of his nephrotic syndrome, and a biopsy showed AL amyloidosis. Bone marrow biopsy performed showed plasma cell myeloma, and the patient was started on induction chemotherapy. Even though the incidence of AL amyloidosis is low before age of 40, we should always perform monoclonal gammopathy workup in patients with nephrotic syndrome regardless of the age. Prompt bone marrow biopsy should be performed to confirm the diagnosis, and starting the treatment as one of the factors that affect the prognosis of AL amyloidosis is early diagnosis.
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