Disparities in primary pancreatic adenocarcinoma survival by Medicaid-status: A national population-based risk analysis

Ganga, Arjun; Kim, Eric J.; Mintzer, G.L.; Adriance, William; Wang, Rachel; Cholankeril, George; Balkrishnan, Rajesh; Somasundar, Ponnandai

doi:10.1016/j.ejso.2023.02.002

Cited by 1 publication

(3 citation statements)

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“…At the same time, the bimodal therapy triggered the formation of new vessels (increased number of smaller vessels with diameters between 0 and 5µm). This effect was not HIF1α-dependent, as evidenced by the observation of a low HIF-1α expression in tumor tissue sections in the absence of necrotic areas with high HIF-1α concentrations, which is reportedly typical of PDAC tumors [ 2 ]. Interestingly, it was accompanied with, at least in tendency, an increased pERK expression.…”

Section: Discussionmentioning

confidence: 99%

“…Pancreatic cancer remains a lethal disease, with as many deaths as new cases [ 1 ]. Over 80% of pancreatic cancers are classified as pancreatic ductal adenocarcinoma (PDAC), and the majority of patients are diagnosed with metastatic or unresectable tumors [ 1 , 2 ] of poor prognosis [ 3 , 4 ]. PDACs are very resistant to oncological treatments.…”

Section: Introductionmentioning

confidence: 99%

“…This includes the upregulation of hypoxia-inducible factor-1α (HIF-1α) [ 20 , 21 ], which in turn upregulates the expression of angiogenic factors such as vascular endothelial growth factor (VEGF) [ 22 ], platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF), among others [ 21 ]. In PDAC, the hypoxic microenvironment is the result of the substantial desmoplastic reactions and the severe extracellular matrix (ECM), which constricts blood vessels [ 2 , 10 ]. Despite this, there is restricted knowledge on how tumor angiogenesis can be more specifically modulated by defined anti-tumor treatments.…”

Section: Introductionmentioning

confidence: 99%

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Local Magnetic Hyperthermia and Systemic Gemcitabine/Paclitaxel Chemotherapy Triggers Neo-Angiogenesis in Orthotopic Pancreatic Tumors without Involvement of Auto/Paracrine Tumor Cell VEGF Signaling and Hypoxia

Maduabuchi,

Tansi,

Faenger

et al. 2023

Cancers

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There is a growing interest in exploring the therapeutically mediated modulation of tumor vascularization of pancreatic cancer, which is known for its poorly perfused tumor microenvironment limiting the delivery of therapeutic agents to the tumor site. Here, we assessed how magnetic hyperthermia in combination with chemotherapy selectively affects growth, the vascular compartment of tumors, and the presence of tumor cells expressing key regulators of angiogenesis. To that purpose, a orthotopic PANC-1 (fluorescent human pancreatic adenocarcinoma) mouse tumor model (Rj:Athym-Foxn1nu/nu) was used. Magnetic hyperthermia was applied alone or in combination with systemic chemotherapy (gemcitabine 50 mg per kg body weight, nab-pacitaxel 30 mg/kg body weight) on days 1 and 7 following magnetic nanoparticle application (dose: 1 mg per 100 mm3 of tumor). We used ultrasound imaging, immunohistochemistry, multi-spectral optoacoustic tomography (MSOT), and hematology to assess the biological parameters mentioned above. We found that magnetic hyperthermia in combination with gemcitabine/paclitaxel chemotherapy was able to impact tumor growth (decreased volumes and Ki67 expression) and to trigger neo-angiogenesis (increased small vessel diameter) as a result of the therapeutically mediated cell damages/stress in tumors. The applied stressors activated specific pro-angiogenic mechanisms, which differed from those seen in hypoxic conditions involving HIF-1α, since (a) treated tumors showed a significant decrease of cells expressing VEGF, CD31, HIF-1α, and neuropilin-1; and (b) the relative tumor blood volume and oxygen level remained unchanged. Neo-angiogenesis seems to be the result of the activation of cell stress pathways, like MAPK pathways (high number of pERK-expressing tumor cells). In the long term, the combination of magnetic hyperthermia and chemotherapy could potentially be applied to transiently modulate tumor angiogenesis and to improve drug accessibility during oncologic therapies of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%