scholarly journals Oxaliplatin-Induced Peripheral Neuropathy Can Be Minimized By Pressurized Regional Intravascular Delivery In An Orthotopic Murine Pancreatic Cancer Model.

2022 ◽  
Author(s):  
Jayanth Surya Narayanan Shankara Narayanan ◽  
Katie Frizzi ◽  
Suna Erdem ◽  
Partha Ray ◽  
David Jaroch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Peripheral Neuropathy ◽  
Tumor Burden ◽  
Cytotoxic Agents ◽  
Ductal Adenocarcinoma ◽  
Tumor Control ◽  
Cancer Model ◽  
Functional Assays ◽  
Venous Infusion ◽  
Regional Delivery

Abstract Purpose: There is a great need to reduce the toxicity of chemotherapy used in the management of pancreatic ductal adenocarcinoma (PDAC). Here we explore if regional pressurized delivery of oxaliplatin can minimize peripheral neuropathy in mice.Methods: We used an orthotopic PDAC mouse model and delivered a single dose of oxaliplatin through the portal vein using a pressure-enabled system (pancreatic retrograde venous infusion, PRVI). We analyzed the effects of PRVI on tumor burden and peripheral neuropathy using histopathological and functional assays.Results: Tumor weights in mice treated with 2 mg/Kg oxaliplatin using PRVI were significantly lower than in mice treated with the same dose systemically. This resulted in reduced peripheral neuropathy signatures in PRVI mice compared to the 20 mg/Kg systemic dose required to achieve similar tumor control.Conclusion: Regional delivery of highly cytotoxic agents using PRVI can reduce the therapeutic dose of these drugs, thereby lowering toxic side effects.

scholarly journals Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1612
Author(s):  
Julie Earl ◽  
Emma Barreto ◽  
María E. Castillo ◽  
Raquel Fuentes ◽  
Mercedes Rodríguez-Garrote ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Somatic Mutation ◽  
Disease Status ◽  
Clinical Analysis ◽  
Cytotoxic Agents ◽  
Disease Stage ◽  
Ductal Adenocarcinoma ◽  
Familial Pancreatic Cancer ◽  
Circulating Free Dna

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

scholarly journals Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma

2016 ◽  
Vol 113 (8) ◽  
pp. 2200-2205 ◽  
Author(s):  
James D. Byrne ◽  
Mohammad R. N. Jajja ◽  
Allison N. Schorzman ◽  
Amanda W. Keeler ◽  
J. Christopher Luft ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Locally Advanced ◽  
Plasma Concentrations ◽  
Advanced Pancreatic Cancer ◽  
Xenograft Model ◽  
Cytotoxic Agents ◽  
Ductal Adenocarcinoma ◽  
Tumor Growth Inhibition ◽  
Iontophoretic Delivery

Poor delivery and systemic toxicity of many cytotoxic agents, such as the recent promising combination chemotherapy regimen of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), restrict their full utility in the treatment of pancreatic cancer. Local delivery of chemotherapies has become possible using iontophoretic devices that are implanted directly onto pancreatic tumors. We have fabricated implantable iontophoretic devices and tested the local iontophoretic delivery of FOLFIRINOX for the treatment of pancreatic cancer in an orthotopic patient-derived xenograft model. Iontophoretic delivery of FOLFIRINOX was found to increase tumor exposure by almost an order of magnitude compared with i.v. delivery with substantially lower plasma concentrations. Mice treated for 7 wk with device FOLFIRINOX experienced significantly greater tumor growth inhibition compared with i.v. FOLFIRINOX. A marker of cell proliferation, Ki-67, was stained, showing a significant reduction in tumor cell proliferation. These data capitalize on the unique ability of an implantable iontophoretic device to deliver much higher concentrations of drug to the tumor compared with i.v. delivery. Local iontophoretic delivery of cytotoxic agents should be considered for the treatment of patients with unresectable nonmetastatic disease and for patients with the need for palliation of local symptoms, and may be considered as a neoadjuvant approach to improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer.

scholarly journals Surgery or Locoregional Approaches for Hepatic Oligometastatic Pancreatic Cancer: Myth, Hope, or Reality?

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1095 ◽  
Author(s):  
Michele Ghidini ◽  
Angelica Petrillo ◽  
Massimiliano Salati ◽  
Shelize Khakoo ◽  
Antonio Varricchio ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Irreversible Electroporation ◽  
Multimodality Treatment ◽  
Ductal Adenocarcinoma ◽  
Surgical Approaches ◽  
Tumor Control ◽  
Recommended Treatment ◽  
Metastatic Setting

Despite extensive research, pancreatic ductal adenocarcinoma (PDAC) remains a difficult-to-treat cancer associated with poor survival. Due to the known aggressive disease biology, palliative chemotherapy is the only routinely recommended treatment in the metastatic setting in patients with adequate performance status. However, in a subset of patients with oligometastatic disease, multimodality treatment with surgery and/or locoregional approaches may provide long-term disease control and prolong survival. In fact, in highly selected cases, median overall survival has been reported to extend to 56 months in patients treated with surgery. In particular, liver and extraregional nodal resections may provide long-term tumor control with acceptable morbidity. Current guidelines do not recommend surgery for patients with metastatic PDAC and, in the case of PDAC with oligometastases, there are no published randomized controlled trials regarding locoregional or surgical approaches. Here we review the literature on surgical and locoregional approaches including radiofrequency ablation, irreversible electroporation, and stereotactic body radiation, and focus on patients with hepatic oligometastatic pancreatic cancer. We provide a summary regarding survival outcomes, morbidity and mortality and discuss selection criteria that may be useful to predict the best outcomes for such strategies.

scholarly journals Scalp Metastasis as the First Presentation of an Underlying Aggressive Pancreatic Cancer

2020 ◽  
Vol 8 ◽  
pp. 232470962093166
Author(s):  
Preethi Ramachandran ◽  
Lakshmi Boyapati ◽  
Gardith Joseph
Keyword(s):  
Pancreatic Cancer ◽  
Metastatic Potential ◽  
Cutaneous Metastasis ◽  
Tumor Burden ◽  
Ductal Adenocarcinoma ◽  
Umbilical Metastasis ◽  
Aggressive Cancer ◽  
Scalp Metastasis ◽  
Scalp Lesion ◽  
Subcutaneous Tissues

Pancreatic ductal adenocarcinoma, an extremely aggressive cancer, has high metastatic potential. Cutaneous metastasis is very uncommon, representing only <10% of all cases, presenting mostly around the umbilical region. Non-umbilical metastasis is even rarer, and the significance remains unknown. In this article, we describe a case of a 76-year-old gentleman who initially presented with an asymptomatic scalp lesion, which on biopsy revealed metastatic adenocarcinoma of pancreatic origin. Detailed workup revealed extremely high tumor burden with metastases involving muscles, subcutaneous tissues, bone, lung, spleen, liver, and colon. Cutaneous involvement in pancreatic cancer represents poor survival with widespread dissemination of the disease. The involvement of some sites and not others and the extreme degree of aggressiveness might reflect subgroups of this cancer with different molecular biology. Identifying these groups may have utility in determining prognosis and stratifying treatment for patients. This will hopefully translate into better diagnostic tests and therapies in the near future.

Therapeutic activity of neutralizing monoclonal antibodies targeting hepatoma-derived growth factor in cancer xenograft models

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2517-2517
Author(s):  
L. Mao ◽  
H. Ren ◽  
Z. Chu ◽  
P. Yuan
Keyword(s):  
Lung Cancer ◽  
Pancreatic Cancer ◽  
Monoclonal Antibodies ◽  
Growth Factor ◽  
Tumor Burden ◽  
Therapeutic Activity ◽  
Tumor Inoculation ◽  
Cancer Model ◽  
Xenograft Models ◽  
The Mean

2517 Background: Hepatoma-derived growth factor (HDGF) is a mitogen for endothelial cells, vessel smooth muscle cells, fibroblasts, as well as some epithelial cells. It is overexpressed in a number of human cancers and its overexpression in tumors strongly correlates with tumor progression, recurrence, and metastasis. We recently showed that down-regulation of HDGF in lung cancer cells reduces tumorigenecity in both in vitro cell and in vivo animal models suggesting HDGF may be of a therapeutic target for cancer. Methods: Recombinant HDGF was used to develop a panel of monoclonal antibodies specifically bind to HDGF. Four antibodies were tested for their therapeutic activity in lung and pancreatic cancer xenograft models. The monoclonal antibodies were administered 250μg/animal (5 mice per group) every 3 days IP when the subcutaneous tumors reached approximately 50 mm3. Results: Two antibodies (C1 and H3) exhibited significant therapeutic activity in A549 lung cancer model whereas H3 also showed a therapeutic effect in MiaPaca-2 pancreatic cancer model. No sign of toxicity in the living animals and histology of major organs were observed in the antibody treated animals. In the A549 model, the mean tumor burden was 960 mm3 for control-IgG treated mice 22 days after tumor inoculation, whereas the mean tumor burdens were 224 mm3 for C1 and 266 mm3 for H3 treated mice (P < 0.05) respectively. In the MiaPaca-2, the mean tumor burden was 994 mm3 for control-IgG treated mice 21 days after tumor inoculation in contrast to 345 mm3 for H3 treated mice (P < 0.05). Consistent with known biologic functions of HDGF, our early morphologic and biomarker analyses suggest that H3 may neutralize tumor cell released HDGF resulting in disruption of tumor stroma and extracellular matrix structures. Conclusions: HDGF is a novel therapeutic target for multiple human cancers and neutralizing monoclonal antibodies targeting HDGF are effective in treating lung and pancreatic cancers in animal models. (Supported by DoD grant DAMD17–01–1-01689–1) No significant financial relationships to disclose.

Comparison of gemcitabine delivery and tumor response in a pressurized pancreatic retrograde venous infusion versus systemic infusion in an orthotopic murine model.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 737-737
Author(s):  
Diego Vicente ◽  
Jayanth Shankara Narayanan ◽  
Partha Ray ◽  
Louis F. Chai ◽  
Suna Erdem ◽  
...  
Keyword(s):  
Immune Cell ◽  
Liver Tumors ◽  
Regional Chemotherapy ◽  
Tumor Burden ◽  
Ductal Adenocarcinoma ◽  
Saline Control ◽  
Systemic Delivery ◽  
Murine Cell Line ◽  
Venous Infusion ◽  
And Control

737 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with limited response to systemic therapy (ST). Elevated tumor interstitial fluid pressures (IFP) inhibit penetration of ST. Regional Pressure Enabled Drug Delivery has recently demonstrated improved response for liver tumors in a clinical trial. However, this delivery method has not been evaluated in PDAC. We compared gemcitabine (Gem) by systemic delivery vs. a novel pressurized Pancreatic Retrograde Venous Infusion (PRVI) method in an orthotopic PDAC mouse model. Methods: PDAC murine cell line (KPC4580P) tumors were transplanted onto the pancreatic tail of C57BL/6J mice. Groups of 15 mice were randomly assigned to PRVI Gem, PRVI saline (Control), or intraperitoneal Gem (Systemic) groups. Five mice from the PRVI and Systemic groups were randomly selected after one hour post infusion to evaluate Gem tumor concentrations by liquid chromatography - tandem mass spectrometry (ng/mg), and the remainder of mice were euthanized after 7 days to evaluate treatment response. Results: Tumor concentrations of Gem were significantly higher following PRVI compared to Systemic (128 vs. 19, p < 0.01) at one hour after treatment. Seven days after treatment, PRVI Gem mice demonstrated lower mean tumor volume (mm3) than Systemic Gem and Control mice (274 vs. 857 vs. 629, p < 0.01), respectively. Histologic evaluation of tumors demonstrated decreased cellularity in the PRVI Gem mice compared to Systemic and Control mice (35 vs. 78 vs. 71%, p = 0.01), respectively. No differences were seen in Ki67% or immune cell infiltrate between groups. Conclusions: PRVI delivery resulted in increased PDAC Gem concentrations and improved treatment responses with decreased tumor burden and cellularity. These findings suggest that pressurized regional chemotherapy infusion overcomes the elevated PDAC IFP and justifies additional translational pre-clinical studies with other chemotherapeutics (including immunomodulating antibodies) with different physicochemical properties.

scholarly journals Chylous Ascites, Unusual Association with Ductal Pancreatic Adenocarcinoma with Plasmacytoid Morphology: A Case Report and Literature Review

2021 ◽  
Vol 07 (03) ◽  
pp. e158-e162
Author(s):  
Catalin Bogdan Satala ◽  
Ioan Jung ◽  
Tivadar Jr. Bara ◽  
Vlad Tudorache ◽  
Simona Gurzu
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Surgical Intervention ◽  
Chylous Ascites ◽  
Distal Portion ◽  
Ductal Adenocarcinoma ◽  
Lymph Vessels ◽  
Lymphangiosis Carcinomatosa ◽  
Ductal Pancreatic Adenocarcinoma ◽  
Tumor Emboli

AbstractChylous ascites represents a relatively uncommon condition. In this paper, we present a case of chyloperitoneum associated with pancreatic ductal adenocarcinoma (PDAC) and a review of literature regarding chylous ascites. A 76-year-old male patient was admitted in emergency department with acute abdomen. A pancreatic cancer was suspected. Subtotal spleno-pancreatectomy, for a nodular mass infiltrating the mild and distal portion of the pancreas, was necessary. During surgical intervention in the peritoneal cavity, a moderate quantity of whitish and thick consistency fluid with milk-like appearance was observed to be accumulated. After examination of the fluid, chyloperitoneum was diagnosed. The histologic examination showed a PDAC, with multiple emboli in lymph vessels, with tumor cells with plasmacytoid morphology, diagnosed as lymphangiosis carcinomatosa. The patient died at 3 weeks after surgical intervention. In patients with pancreatic cancer and chylous ascites, suspicion of tumor-related blockage of the lymphatic flow should be suspected. Prognosis of PDAC should be evaluated not only based on the number of lymph node metastases, but also considering the number of lymph vessels with tumor emboli and the architecture of tumor cells. This is the first reported case of a PDAC with plasmacytoid morphology of lymphangiosis carcinomatosa.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

scholarly journals Exercise efficacy and prescription during treatment for pancreatic ductal adenocarcinoma: a systematic review

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dominic O’Connor ◽  
Malcolm Brown ◽  
Martin Eatock ◽  
Richard C. Turkington ◽  
Gillian Prue
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Physical Function ◽  
Meta Analysis ◽  
Ductal Adenocarcinoma ◽  
Key Stakeholders ◽  
The Impact

Abstract Background Surgical resection remains the only curative treatment for pancreatic cancer and is associated with significant post-operative morbidity and mortality. Patients eligible for surgery, increasingly receive neo-adjuvant therapy before surgery or adjuvant therapy afterward, inherently exposing them to toxicity. As such, optimizing physical function through exercise during treatment remains imperative to optimize quality of life either before surgery or during rehabilitation. However, current exercise efficacy and prescription in pancreatic cancer is unknown. Therefore, this study aims to summarise the published literature on exercise studies conducted in patients with pancreatic cancer undergoing treatment with a focus on determining the current prescription and progression patterns being used in this population. Methods A systematic review of four databases identified studies evaluating the effects of exercise on aerobic fitness, muscle strength, physical function, body composition, fatigue and quality of life in participants with pancreatic cancer undergoing treatment, published up to 24 July 2020. Two reviewers independently reviewed and appraised the methodological quality of each study. Results Twelve studies with a total of 300 participants were included. Heterogeneity of the literature prevented meta-analysis. Exercise was associated with improvements in outcomes; however, study quality was variable with the majority of studies receiving a weak rating. Conclusions High quality evidence regarding the efficacy and prescription of exercise in pancreatic cancer is lacking. Well-designed trials, which have received feedback and input from key stakeholders prior to implementation, are required to examine the impact of exercise in pancreatic cancer on key cancer related health outcomes.

scholarly journals Ca2+ Signaling and Its Potential Targeting in Pancreatic Ductal Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3085
Author(s):  
Louay Bettaieb ◽  
Maxime Brulé ◽  
Axel Chomy ◽  
Mel Diedro ◽  
Malory Fruit ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Exocrine Pancreas ◽  
Ductal Carcinoma ◽  
Ductal Adenocarcinoma ◽  
Molecular Devices ◽  
Pancreatic Ductal Carcinoma ◽  
Aberrant Expression ◽  
Common Cause ◽  
Cancer Hallmarks ◽  
Cancer Mutations

Pancreatic cancer (PC) is a major cause of cancer-associated mortality in Western countries (and estimated to be the second cause of cancer deaths by 2030). The main form of PC is pancreatic adenocarcinoma, which is the fourth most common cause of cancer-related death, and this situation has remained virtually unchanged for several decades. Pancreatic ductal adenocarcinoma (PDAC) is inherently linked to the unique physiology and microenvironment of the exocrine pancreas, such as pH, mechanical stress, and hypoxia. Of them, calcium (Ca2+) signals, being pivotal molecular devices in sensing and integrating signals from the microenvironment, are emerging to be particularly relevant in cancer. Mutations or aberrant expression of key proteins that control Ca2+ levels can cause deregulation of Ca2+-dependent effectors that control signaling pathways determining the cells’ behavior in a way that promotes pathophysiological cancer hallmarks, such as enhanced proliferation, survival and invasion. So far, it is essentially unknown how the cancer-associated Ca2+ signaling is regulated within the characteristic landscape of PDAC. This work provides a complete overview of the Ca2+ signaling and its main players in PDAC. Special consideration is given to the Ca2+ signaling as a potential target in PDAC treatment and its role in drug resistance.

Sign in / Sign up

Export Citation Format

Share Document