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Pancreatic cancer immunotherapy

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https://www.readbyqxmd.com/read/29909021/nf%C3%AE%C2%BAb-in-pancreatic-stellate-cells-reduces-infiltration-of-tumors-by-cytotoxic-t-cells-and-killing-of-cancer-cells-via-upregulation-of-cxcl12
#1
Bharti Garg, Bhuwan Giri, Shrey Modi, Vrishketan Sethi, Iris Castro, Oliver Umland, Yuguang Ban, Shweta Lavania, Rajinder Dawra, Sulagna Banerjee, Selwyn Vickers, Nipun B Merchant, Steven Xi Chen, Eli Gilboa, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja
BACKGROUND & AIMS: Immunotherapies are ineffective against pancreatic cancer. We investigated whether the activity of nuclear factor (NF)κB in pancreatic stromal cells contributes to an environment that suppresses anti-tumor immune response. METHODS: Pancreata of C57BL/6 or Rag1-/- mice were given pancreatic injections of a combination of KrasG12D/+; Trp53 R172H/+; Pdx-1cre (KPC) pancreatic cancer cells and pancreatic stellate cells (PSCs) extracted from C57BL/6 (control) or mice with disruption of the gene encoding the NFkB p50 subunit (Nfkb1 or p50-/- mice)...
June 14, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29899472/imaging-egfr-and-her3-through-89-zr-labeled-mehd7945a-duligotuzumab
#2
Brooke N McKnight, Akhila N W Kuda-Wedagedara, Kuntal K Sevak, Dalya Abdel-Atti, Wendy N Wiesend, Anson Ku, Dakshnamurthy Selvakumar, Sean D Carlin, Jason S Lewis, Nerissa T Viola-Villegas
Tumor resistance to treatment paved the way toward the development of single agent drugs that target multiple molecular signatures amplified within the malignancy. The discovered crosstalk between EGFR and HER3 as well as the role of HER3 in mediating EGFR resistance made these two receptor tyrosine kinases attractive targets. MEHD7945A or duligotuzumab is a single immunotherapy agent that dually targets both molecular signatures. In this study, a positron emission tomography (PET) companion diagnostic to MEHD7945A is reported and evaluated in pancreatic cancer...
June 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29898269/metastatic-pancreatic-ductal-adenocarcinoma-diagnosis-and-treatment-with-a-view-to-the-future
#3
Adrian M J Pokorny, Venessa T Chin, Adnan M Nagrial, Desmond Yip, Lorraine A Chantrill
Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a lethal disease with a poor 5-year survival. Systemic treatments can be used to control symptoms and prolong life. Cytotoxic chemotherapies are commonly administered, with combination treatments, such as fluorouracil, folinic acid, irinotecan and oxaliplatin (FOLFIRINOX) or nab-paclitaxel and gemcitabine showing the largest clinical benefits. Newer genomic classifications of PDAC may provide a rationale for targeted therapies or immunotherapies, although at present these remain largely experimental...
June 2018: Internal Medicine Journal
https://www.readbyqxmd.com/read/29895293/robotic-treatment-of-oligometastatic-kidney-tumor-with-synchronous-pancreatic-metastasis-case-report-and-review-of-the-literature
#4
Andrea Boni, Giovanni Cochetti, Stefano Ascani, Michele Del Zingaro, Francesca Quadrini, Alessio Paladini, Diego Cocca, Ettore Mearini
BACKGROUND: The management of metastatic Renal Cell Carcinoma (RCC) has changed dramatically in the last 20 years, and the role of surgery in the immunotherapy's era is under debate. Metastatic lesions interesting pancreas are infrequent, but those harbouring from RCC have an high incidence. If metachronous resections are not rare, synchronous resection of primary RCC and its pancreatic metastasis is uncommonly reported, and accounts for a bad prognosis. CASE PRESENTATION: We report the case of a 68 years old woman, who presented hematuria at hospital incoming, with radiological appearance of a 13 cm left renal mass, with a 2...
June 13, 2018: BMC Surgery
https://www.readbyqxmd.com/read/29880440/adverse-effects-of-immune-checkpoint-therapy-in-cancer-patients-visiting-the-emergency-department-of-a-comprehensive-cancer-center
#5
Imad El Majzoub, Aiham Qdaisat, Kyaw Z Thein, Myint A Win, Myat M Han, Kalen Jacobson, Patrick S Chaftari, Michael Prejean, Cielito Reyes-Gibby, Sai-Ching J Yeung
STUDY OBJECTIVE: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs). METHODS: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016...
June 4, 2018: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/29868007/pancreatic-ductal-adenocarcinoma-a-strong-imbalance-of-good-and-bad-immunological-cops-in-the-tumor-microenvironment
#6
REVIEW
Etienne D Foucher, Clément Ghigo, Salem Chouaib, Jérôme Galon, Juan Iovanna, Daniel Olive
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers with very few available treatments. For many decades, gemcitabine was the only treatment for patients with PDAC. A recent attempt to improve patient survival by combining this chemotherapy with FOLFIRINOX and nab-paclitaxel failed and instead resulted in increased toxicity. Novel therapies are urgently required to improve PDAC patient survival. New treatments in other cancers such as melanoma, non-small-cell lung cancer, and renal cancer have emerged, based on immunotherapy targeting the immune checkpoints cytotoxic T-lymphocyte-associated antigen 4 or programmed death 1 ligand...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29860986/immunotherapy-and-prevention-of-pancreatic-cancer
#7
REVIEW
Alexander H Morrison, Katelyn T Byrne, Robert H Vonderheide
Pancreatic cancer is the third-leading cause of cancer mortality in the USA, recently surpassing breast cancer. A key component of pancreatic cancer's lethality is its acquired immune privilege, which is driven by an immunosuppressive microenvironment, poor T cell infiltration, and a low mutational burden. Although immunotherapies such as checkpoint blockade or engineered T cells have yet to demonstrate efficacy, a growing body of evidence suggests that orthogonal combinations of these and other strategies could unlock immunotherapy in pancreatic cancer...
June 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29844122/radiotherapy-and-cd40-activation-separately-augment-immunity-to-checkpoint-blockade-in-cancer
#8
Andrew J Rech, Hannah Dada, Jonathan J Kotzin, Jorge Henao-Mejia, Andy J Minn, Christina Twyman-Saint Victor, Robert H Vonderheide
Immunotherapy in pancreatic ductal adenocarcinoma (PDA) remains a difficult clinical problem despite success in other disease types with immune checkpoint blockade (ICB) and chimeric antigen receptor T cell therapy. Mechanisms driving immunosuppression and poor T cell infiltration in PDA are incompletely understood. Here we use genetically engineered mouse models of PDA that recapitulate hallmarks of human disease to demonstrate that CD40 pathway activation is required for clinical response to radiotherapy (RT) and ICB with αCTLA-4 and αPD-1...
May 29, 2018: Cancer Research
https://www.readbyqxmd.com/read/29771768/high-density-infiltration-of-v-domain-immunoglobulin-suppressor-of-t-cell-activation-up-regulated-immune-cells-in-human-pancreatic-cancer
#9
Jinʼe Liu, Xiaoxue Xie, Chunxiao Xuan, Tingting Li, Lanlan Wang, Lianghong Teng, Jun Liu
V-domain immunoglobulin suppressor of T-cell activation (VISTA) is constitutively expressed in hematopoietic lineage and is highly up-regulated in tumor infiltrated myeloid cells and regulatory T cells in animal models. However, its expression in human pancreatic tumor microenvironment remains unknown. In this research, we aimed at the expression of VISTA in human pancreatic cancer samples. METHODS: We performed immunohistochemistry to determine VISTA expression in human pancreatic cancer samples...
May 15, 2018: Pancreas
https://www.readbyqxmd.com/read/29765563/targeted-therapies-in-the-management-of-locally-advanced-and-metastatic-pancreatic-cancer-a-systematic-review
#10
REVIEW
Anjali V Sheahan, Andrew V Biankin, Christopher R Parish, Levon M Khachigian
Pancreatic cancer has a dismal prognosis particularly in patients presenting with unresectable tumors. We performed a bibliometric analysis of clinical trials for pancreatic cancer conducted between 2014-2016 focusing on patients that presented with unresectable (locally advanced or metastatic) tumors. We discuss a range of studies that employed FOLFIRINOX, the gemcitabine + nab-paclitaxel combination and studies that used molecularly-targeted therapy. Major areas of focus have been dual targeting of EGFR and VEGFR, immunotherapy or a multimodal approach - combining chemotherapy with radiotherapy...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29728788/chimeric-antigen-receptor-t-cell-therapy-in-pancreatic-cancer-from-research-to-practice
#11
REVIEW
Vishal Jindal, Ena Arora, Muhammad Masab, Sorab Gupta
Chimeric antigen receptor (CAR) T cell therapy is genetically engineered tumor antigen-specific anticancer immunotherapy, which after showing great success in hematological malignancies is currently being tried in advanced solid tumors like pancreatic cancer. Immunosuppressive tumor microenvironment and dense fibrous stroma are some of the limitation in the success of this novel therapy. However, genetic modifications and combination therapy is the topic of the research to improve its efficacy. In this article, we summarize the current state of knowledge, limitations, and future prospects for CAR T cell therapy in pancreatic cancer...
May 4, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29717230/therapeutic-developments-in-pancreatic-cancer-current-and-future-perspectives
#12
REVIEW
John P Neoptolemos, Jörg Kleeff, Patrick Michl, Eithne Costello, William Greenhalf, Daniel H Palmer
The overall 5-year survival for pancreatic cancer has changed little over the past few decades, and pancreatic cancer is predicted to be the second leading cause of cancer-related mortality in the next decade in Western countries. The past few years, however, have seen improvements in first-line and second-line palliative therapies and considerable progress in increasing survival with adjuvant treatment. The use of biomarkers to help define treatment and the potential of neoadjuvant therapies also offer opportunities to improve outcomes...
May 1, 2018: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29707526/combination-immunotherapy-approaches-for-pancreatic-cancer-treatment
#13
REVIEW
Xianliang Cheng, Gang Zhao, Yunqi Zhao
Pancreatic ductal adenocarcinoma is a lethal malignant disease with a very low medium survival. Currently, metastatic pancreatic cancer poorly responds to conventional treatments and exhibits an acute resistance to most chemotherapy. Few approaches have been shown to be effective for metastatic pancreatic cancer treatment. Novel therapeutic approaches to treat patients with pancreatic adenocarcinoma are in great demand. Last decades, immunotherapies have been evaluated in clinical trials and received great success in many types of cancers...
2018: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29705789/immunotherapy-and-combination-strategies-in-pancreatic-cancer-current-status-and-emerging-trends
#14
Phyllis F Cheung, Manfred Lutz, Jens T Siveke
Pancreatic cancer is among the most aggressive malignancies with no effective therapeutic options thus far. Immunotherapy has recently emerged as a promising alternative for the treatment of various solid tumors. In particular, promising results in clinical trials were observed for therapies targeting immune checkpoint molecules. Efforts have been put into investigating the potential of immunotherapy in treating pancreatic cancer. While most of the clinical trial results are still being awaited, several intrinsic features of pancreatic cancer such as low mutational load and the presence of highly immunosuppressive desmoplasia significantly hamper the efficacy of immunotherapy in this disease...
2018: Oncology Research and Treatment
https://www.readbyqxmd.com/read/29668571/evaluating-for-pseudoprogression-in-colorectal-and-pancreatic-tumors-treated-with-immunotherapy
#15
Christine M Parseghian, Madhavi Patnana, Priya Bhosale, Kenneth R Hess, Ya-Chen Tina Shih, Bumyang Kim, Scott Kopetz, Michael J Overman, Gauri R Varadhachary, Milind Javle, Aung Naing, Sarina Piha-Paul, David Hong, Hung Le, Vivek Subbiah, Shubham Pant
Pseudoprogression has been observed in patients with various tumor types treated with immunotherapy. However, the frequency of pseudoprogression is unknown in gastrointestinal malignancies. Metastatic colorectal cancer (mCRC) and advanced pancreatic ductal adenocarcinoma (PDAC) patients who progressed on treatment with immunotherapy beyond RECIST version 1.1 criteria were analyzed. Degree of progression, tumor markers, time to progression, overall survival, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and costs were analyzed for patients treated beyond progression (TBP) and not treated beyond progression...
July 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#16
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29660367/natural-killer-cells-and-their-therapeutic-role-in-pancreatic-cancer-a-systematic-review
#17
REVIEW
Jonas R M Van Audenaerde, Geert Roeyen, Phillip K Darcy, Michael H Kershaw, M Peeters, Evelien L J Smits
Pancreatic cancer is among the three deadliest cancers worldwide with the lowest 5-year survival of all cancers. Despite all efforts, therapeutic improvements have barely been made over the last decade. Even recent highly promising targeted and immunotherapeutic approaches did not live up to their expectations. Therefore, other horizons have to be explored. Natural Killer (NK) cells are gaining more and more interest as a highly attractive target for cancer immunotherapies, both as pharmaceutical target and for cell therapies...
April 13, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29623227/fulminant-diabetes-in-a-patient-with-advanced-melanoma-on-nivolumab
#18
Nora Chokr, Hafsa Farooq, Elizabeth Guadalupe
Background: Anti-PD-1 agents were approved for advanced melanoma after the landmark trial Checkmate-037. Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells in genetically predisposed people. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy. Case: A 61-year-old male with advanced melanoma presented with a three-day history of nausea, vomiting, and malaise...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29617184/targeting-interleukin-22-for-cancer-therapy
#19
Anamarija Markota, Stefan Endres, Sebastian Kobold
Interleukin-22 (IL-22) is a member of IL-10 family of cytokines. IL-22 induces proliferative and anti-apoptotic signaling pathways and production of anti-microbial molecules that enhance tissue regeneration and host defense. IL-22 has also been identified as a cancer-promoting cytokine since deregulation of the IL-22-IL-22R1 system is linked to different cancer entities including lung, breast, gastric, pancreatic and colon cancers. T cells and innate lymphoid cells are the main cellular sources of IL-22. Expression of its specific receptor IL-22R1 is restricted to the non-hematopoietic cells which makes the IL-22-IL-22R1 pathway an attractive target for anti-cancer therapy...
April 4, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29615613/multi-omics-analysis-reveals-neoantigen-independent-immune-cell-infiltration-in-copy-number-driven-cancers
#20
Daniel J McGrail, Lorenzo Federico, Yongsheng Li, Hui Dai, Yiling Lu, Gordon B Mills, Song Yi, Shiaw-Yih Lin, Nidhi Sahni
To realize the full potential of immunotherapy, it is critical to understand the drivers of tumor infiltration by immune cells. Previous studies have linked immune infiltration with tumor neoantigen levels, but the broad applicability of this concept remains unknown. Here, we find that while this observation is true across cancers characterized by recurrent mutations, it does not hold for cancers driven by recurrent copy number alterations, such as breast and pancreatic tumors. To understand immune invasion in these cancers, we developed an integrative multi-omics framework, identifying the DNA damage response protein ATM as a driver of cytokine production leading to increased immune infiltration...
April 3, 2018: Nature Communications
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