scholarly journals Investigation of factors associated with reduced clinical benefits of personalized peptide vaccination for pancreatic cancer

2020 ◽  
Vol 14 (2) ◽  
Author(s):  
Yoshihiro Uchino ◽  
Daisuke Muroya ◽  
Munehiro Yoshitomi ◽  
Shigeki Shichijo ◽  
Akira Yamada ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Peptide Vaccination ◽  
Factors Associated ◽  
Clinical Benefits

scholarly journals Factors associated with quality of care for patients with pancreatic cancer in Australia

2016 ◽  
Vol 205 (10) ◽  
pp. 459-465 ◽  
Author(s):  
Elizabeth A Burmeister ◽  
Dianne L O'Connell ◽  
Susan J Jordan ◽  
David Goldstein ◽  
Neil Merrett ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Quality Of Care ◽  
Factors Associated

scholarly journals Factors Associated with Ketamine Use in Pancreatic Cancer Patient in a Single Hospice Center

2016 ◽  
Vol 19 (3) ◽  
pp. 249-255
Author(s):  
Kyung Min Kwon ◽  
Yong Joo Lee ◽  
Chang Jin Choi ◽  
Chul Min Kim ◽  
Jo Hi Yoon ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patient ◽  
Pancreatic Cancer Patient ◽  
Factors Associated

Tu1905 Exploring the Relevance and Effect Size of Factors Associated With the Outcome of Pancreatic Cancer Screening in High-Risk Individuals

2014 ◽  
Vol 146 (5) ◽  
pp. S-869
Author(s):  
Inge M. de Kok ◽  
Femme Harinck ◽  
Ingrid C. Konings ◽  
Iris Lansdorp-Vogelaar ◽  
Paul Fockens ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Screening ◽  
High Risk ◽  
Effect Size ◽  
Factors Associated ◽  
Pancreatic Cancer Screening

scholarly journals Genomic Features and Clinical Management of Patients with Hereditary Pancreatic Cancer Syndromes and Familial Pancreatic Cancer

2019 ◽  
Vol 20 (3) ◽  
pp. 561 ◽  
Author(s):  
Akihiro Ohmoto ◽  
Shinichi Yachida ◽  
Chigusa Morizane
Keyword(s):  
Pancreatic Cancer ◽  
Checkpoint Inhibitors ◽  
Susceptibility Gene ◽  
Treatment Strategies ◽  
Familial Pancreatic Cancer ◽  
Cancer Syndrome ◽  
Increased Risk ◽  
Clinical Benefits ◽  
Surveillance Programs ◽  
Cancer Syndromes

Pancreatic cancer (PC) is one of the most devastating malignancies; it has a 5-year survival rate of only 9%, and novel treatment strategies are urgently needed. While most PC cases occur sporadically, PC associated with hereditary syndromes or familial PC (FPC; defined as an individual having two or more first-degree relatives diagnosed with PC) accounts for about 10% of cases. Hereditary cancer syndromes associated with increased risk for PC include Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma, familial adenomatous polyposis, Lynch syndrome and hereditary breast and ovarian cancer syndrome. Next-generation sequencing of FPC patients has uncovered new susceptibility genes such as PALB2 and ATM, which participate in homologous recombination repair, and further investigations are in progress. Previous studies have demonstrated that some sporadic cases that do not fulfil FPC criteria also harbor similar mutations, and so genomic testing based on family history might overlook some susceptibility gene carriers. There are no established screening procedures for high-risk unaffected cases, and it is not clear whether surveillance programs would have clinical benefits. In terms of treatment, poly (ADP-ribose) polymerase inhibitors for BRCA-mutated cases or immune checkpoint inhibitors for mismatch repair deficient cases are promising, and clinical trials of these agents are underway.

scholarly journals Personalized Kampo Medicine Facilitated Both Cytotoxic T Lymphocyte Response and Clinical Benefits Induced by Personalized Peptide Vaccination for Advanced Esophageal Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Daisuke Muroya ◽  
Shigeru Yutani ◽  
Shigeki Shichijo ◽  
Akira Yamada ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Clinical Study ◽  
Cytotoxic T Lymphocyte ◽  
Progression Free Survival ◽  
Kampo Medicine ◽  
Prospective Clinical Study ◽  
Advanced Esophageal Cancer ◽  
Peptide Vaccination ◽  
Clinical Benefits ◽  
Ctl Responses

We retrospectively evaluated if personalized Kampo medicine (PKM) could facilitate CTL responses and clinical benefits induced by personalized peptide vaccination (PPV), in which HLA-matched vaccines were selected and administered based on the preexisting host immunity, for advanced esophageal cancer (aEC) patients. Among 34 aEC patients entered in the clinical study, 23 patients received PKM and PPV without (n=12) or with chemotherapy (n=11), while the remaining 11 patients did not receive PKM but received PPV without (n=6) or with chemotherapy (n=5), respectively. Incidence of adverse events was significantly lower or higher in PKM and PPV arm (n=23) or PPV and chemotherapy arm (n=16) as compared to that of the counter arm (n=11or 18), respectively. Postvaccination PBMCs from the patients undergoing PKM and PPV showed significantly higher CTL responses as compared to the counter arm. The median progression-free survival (PFS) or median survival time (MST) of 34 patients was 2.9 or 7.6 months, respectively. The combination therapy in PPV and PKM arm, but not that in PPV and chemotherapy arm, significantly (P=0.02) prolonged MST. These results could warrant a next step of prospective clinical study of PKM and PPV for aEC patients.

Immunological evaluation of personalized peptide vaccination with gemcitabine for advance pancreatic cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14029-14029 ◽  
Author(s):  
H. Yanagimoto ◽  
T. Mine ◽  
K. Yamamoto ◽  
S. Satoi ◽  
S. Honma ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Outpatient Basis ◽  
Igg Antibodies ◽  
Peptide Vaccination ◽  
Post Vaccination ◽  
Level 3 ◽  
Specific Igg ◽  
Level 2 ◽  
Specific Igg Antibodies

14029 Background: A phase I clinical study was performed to determine safety and immunogenicity of personalized peptide vaccination with gemcitabine (GEM) in advanced pancreatic cancer patients (APC). Methods: Thirteen human histocompatibility leukocyte antigen (HLA)-A24+ or A2+ patients with unresectable (n=10) or recurrent (n=3) pancreatic cancer were treated with GEM plus up to four peptides that were positive for pre-vaccination measurement of peptide-specific IgG antibodies and/or cytotoxic T lymphocyte (CTL) precursors in the circulation (personalized peptide vaccine). GEM was administered at 1000mg/m2 as a 30-min intravenous infusion once a week for three week, followed by 1 week of rest. All patients were treated on outpatient basis. The cycle was repeated every 8 weeks. Results: Peptide doses of vaccination per week were planned as follows: level 1, 1mg; level 2, 2mg; and level 3, 3mg. The main grade 3 toxicities observed during the first cycle in each level were neutropenia (15%), anemia (23%) and thrombocytopenia (15%). No significant differences in the toxicities were found between each level. There was no dose limiting toxicity (DLT) observed in each level. Augmentation of peptide-specific CTL responses in the post-vaccination peripheral blood mononuclear cells was observed in each level, while increased titer of peptide-specific IgG antibodies was observed in the post-vaccination plasma in level 2 and level 3. Applicable responses were no complete response, two partial responses (15%), and 7 stable diseases (55%). Nevertheless 7 patients of them (54%) were under the second-line chemotherapy, disease control rate was 70%, the median TTP (time to progression) was 18.5 weeks and the MST (median survival time) was 7.6 months in this study. Conclusions: The combination therapy of personalized peptide vaccination with GEM for APC patients is feasible and safe. Because of positive immune responses under a full dose of GEM, the peptide vaccination of 3 mg is recommended. No significant financial relationships to disclose.

Effect of NVP-BEZ235, a dual PI3K/mTOR inhibitor, on chemotherapy and antiangiogenic response in pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 243-243 ◽  
Author(s):  
Katherine T. Ostapoff ◽  
Niranjan Awasthi ◽  
Peter L. Yen ◽  
Changhua Zhang ◽  
Margaret A. Schwarz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Mtor Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Animal Experiments ◽  
Ductal Adenocarcinoma ◽  
Clinical Benefits ◽  
Induced Apoptosis

243 Background: The phosphatidylinositol-3-kinase (PI3K)/AKT and mammalian target of rapamycin (mTOR) signaling pathway dysregulation is a prominent feature of pancreatic ductal adenocarcinoma (PDAC). Gemcitabine (GEM), a standard systemic treatment for PDAC, has limited clinical benefits. The present study investigated the effects of NVP-BEZ235 (BEZ235), a novel dual PI3K/mTOR inhibitor, in combination with gemcitabine and endothelial monocyte activating polypeptide II (EMAP) in experimental PDAC. Methods: Protein expression and cell proliferation were analyzed by Western blotting and WST-1 assay. Animal experiments were performed in murine xenografts. Results: BEZ235 inhibited phospho-AKT (Ser473) and phospho-mTOR (Ser2448) expression in PDAC (AsPC-1), endothelial (HUVECs) and fibroblast (WI-38) cells. NVP-BEZ235 also caused a significant dephosphorylation of downstream mTORC1 target proteins phospho-p70 S6K (Thr389) and phospho-4E-BP1 (Thr37/46). In vitro 72-hour proliferation of four PDAC cell lines was significantly inhibited by BEZ235. Additive effects on proliferation inhibition were observed in the BEZ235 and GEM combination in PDAC cells and in combination of BEZ235 or EMAP with gemcitabine in HUVECs and WI-38 cells. BEZ235, alone or in combination with GEM and EMAP, induced apoptosis in AsPC-1, HUVECs and WI-38 cells as observed by increased expression of cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and caspase-3 proteins. PDAC in vivo therapy demonstrated that compared to controls (median survival: 16 days), animal survival increased after BEZ235 and EMAP therapy alone (both 21 days) and GEM monotherapy (28 days). Further increases in survival occurred in combination therapy groups BEZ235+GEM (30 days, p=0.007), BEZ235+EMAP (27 days, p=0.02), GEM+EMAP (31 days, p=0.001) and BEZ235+GEM +EMAP (33 days, p=0.004). Conclusions: BEZ235 has experimental PDAC antitumor activity in vitro and in vivo that can be enhanced in combination with cytotoxic (GEM) and antiendothelial (EMAP) agents. These findings demonstrate advantages of combination therapy strategies targeting multiple pathways in pancreatic cancer treatment.

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