Article
Biochemistry & Molecular Biology
David J. Wooten, Indu Sinha, Raghu Sinha
Summary: The study aimed to investigate the combination treatment of selenium and Gemcitabine on pancreatic cancer. The results showed that the combination had anti-proliferative and apoptosis-inducing effects on pancreatic cancer cells in vitro, and the combination performed better in both 2D and 3D growth environments.
Review
Oncology
Naotake Funamizu, Masahiko Honjo, Kei Tamura, Katsunori Sakamoto, Kohei Ogawa, Yasutsugu Takada
Summary: This review summarizes the current evidence for the role of microRNAs (miRNAs) in the mechanism of chemoresistance in pancreatic cancer. Pancreatic cancer has a poor prognosis due to its late discovery, aggressive nature, and chemoresistance. Aberrant miRNAs have been found to induce chemoresistance in pancreatic cancer, but the exact molecular mechanisms are still unclear. Novel biomarkers and therapeutic strategies for chemoresistance are urgently needed to improve patient outcomes.
Article
Oncology
Karen Aughton, Nils O. Elander, Anthony Evans, Richard Jackson, Fiona Campbell, Eithne Costello, Christopher M. Halloran, John R. Mackey, Andrew G. Scarfe, Juan W. Valle, Ross Carter, David Cunningham, Niall C. Tebbutt, David Goldstein, Jennifer Shannon, Bengt Glimelius, Thilo Hackert, Richard M. Charnley, Alan Anthoney, Markus M. Lerch, Julia Mayerle, Daniel H. Palmer, Markus W. Buechler, Paula Ghaneh, John P. Neoptolemos, William Greenhalf
Summary: Recent clinical trials indicate that combination therapies with gemcitabine or 5-fluorouracil (5-FU) show survival benefits for pancreatic cancer patients. The nucleoside transporter hENT1 predicts benefits from gemcitabine over 5-FU. Cytidine deaminase (CDA) affects gemcitabine efficacy. High hENT1 protein is associated with better survival with gemcitabine treatment, while low CDA transcript levels are prognostic regardless of treatment arm.
Article
Pharmacology & Pharmacy
Da Eun Lee, Hyeon Woong Kang, So Yi Kim, Myeong Jin Kim, Jae Woong Jeong, Woosol Chris Hong, Sungsoon Fang, Hyung Sun Kim, Yun Sun Lee, Hyo Jung Kim, Joon Seong Park
Summary: This study demonstrates that the combination of ivermectin and gemcitabine effectively suppresses pancreatic cancer by inhibiting cell proliferation and inducing cell apoptosis through cell cycle arrest and mitochondrial dysfunction. In vivo experiments also support the tumor-inhibiting effect of this combination treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Astrid Z. Johansen, Sif I. Novitski, Jessica X. Hjaltelin, Susann Theile, Mogens K. Boisen, Soren Brunak, Daniel H. Madsen, Dorte L. Nielsen, Inna M. Chen
Summary: In this study, the association between plasma YKL-40 levels and clinical benefit and survival in patients with metastatic pancreatic cancer (mPC) receiving immune checkpoint inhibitors (ICIs) and stereotactic body radiotherapy (SBRT) was investigated. The results showed that elevated baseline plasma YKL-40 levels were associated with shorter overall survival, while a greater than 40% decrease in plasma YKL-40 levels during treatment was associated with longer progression-free survival and overall survival. These findings suggest that YKL-40 may serve as a potential biomarker for patients treated with immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Genta Ito, Kazuyoshi Kawakami, Takeshi Aoyama, Takashi Yokokawa, Masashi Nakamura, Masato Ozaka, Naoki Sasahira, Masayuki Hashiguchi, Hayato Kizaki, Toshihiro Hama, Satoko Hori
Summary: Combination therapy with gemcitabine and nanoparticle albumin-bound paclitaxel (GnP therapy) can significantly prolong the survival of pancreatic cancer patients but may also lead to severe neutropenia. This study identified low ANC, high T-Bil, and low CRP as risk factors for Grade 3/4 neutropenia during GnP therapy. Patients with these risk factors should be closely monitored for adverse events.
Article
Oncology
Yuhan Yang, Haitao Gu, Kundong Zhang, Zengya Guo, Xiaofeng Wang, Qingyun Wei, Ling Weng, Xuan Han, Yan Lv, Meng Cao, Peng Cao, Chen Huang, Zhengjun Qiu
Summary: This study aimed to evaluate the potential of exosomes from cancer cells to predict chemoresistance in pancreatic cancer (PC) and explore the molecular mechanisms. Exosomal ACADM was found to be strongly correlated with gemcitabine sensitivity in vivo and can be used as a predictor for postoperative gemcitabine chemosensitivity in pancreatic patients. ACADM was also observed to regulate the gemcitabine response by affecting ferroptosis through GPX4 and mevalonate pathways.
Article
Biochemistry & Molecular Biology
Natalia E. Cortez, Suraj Pathak, Cecilia Rodriguez Lanzi, Brian V. Hong, Ryman Crone, Rasheed Sule, Fangyi Wang, Shuai Chen, Aldrin V. Gomes, Keith Baar, Gerardo G. Mackenzie
Summary: Cancer-associated cachexia (CAC) contributes to pancreatic ductal adenocarcinoma (PDAC) mortality. Dietary interventions, such as a ketogenic diet (KD), combined with gemcitabine has been shown to enhance survival in a mouse model of PDAC. This study investigates the effect of KD and gemcitabine on skeletal muscle mass in PDAC mice. The results suggest that KD can preserve muscle mass and further research is needed to determine its clinical efficacy in combating CAC in PDAC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Esther N. Pijnappel, Nienke P. M. Wassenaar, Oliver J. Gurney-Champion, Remy Klaassen, Koen van der Lee, Marjolein C. H. Pleunis-van Empel, Dick J. Richel, Marie C. Legdeur, Aart J. Nederveen, Hanneke W. M. van Laarhoven, Johanna W. Wilmink
Summary: The combination of LDE225 with gemcitabine and nab-paclitaxel was well-tolerated and effective in patients with metastatic PDAC, especially in those with poor baseline tumor perfusion. These results suggest a potential clinical benefit of this combination therapy in patients who have received prior FOLFIRINOX treatment.
Article
Oncology
Stefano Cascinu, Rossana Berardi, Roberto Bianco, Domenico Bilancia, Alberto Zaniboni, Daris Ferrari, Stefania Mosconi, Andrea Spallanzani, Luigi Cavanna, Silvana Leo, Francesca Negri, Giordano D. Beretta, Alberto Sobrero, Maria Banzi, Alberto Morabito, Alessandro Bittoni, Roberta Marciano, Domenica Ferrara, Silvia Noventa, Maria C. Piccirillo, Roberto Labianca, Cristina Mosconi, Andrea Casadei Gardini, Ciro Gallo, Francesco Perrone
Summary: The combination chemotherapy regimen of Nab-paclitaxel and Gemcitabine showed superior efficacy compared to Gemcitabine alone in patients with unresectable locally advanced pancreatic cancer, reducing disease progression rate and distant relapses, and improving progression-free survival. This randomized trial provides evidence supporting the use of combination chemotherapy in this setting.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Oncology
Tiziano Lottini, Claudia Duranti, Jessica Iorio, Michele Martinelli, Rossella Colasurdo, Franco Nicolas D'Alessandro, Matteo Buonamici, Stefano Coppola, Valentina Devescovi, Vincenzo La Vaccara, Alessandro Coppola, Roberto Coppola, Elena Lastraioli, Annarosa Arcangeli
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with a poor prognosis. The standard chemotherapy drug Gemcitabine has limited efficacy and high toxicity. This study introduces a new therapeutic strategy using a single chain bispecific antibody (scDb-hERG1-beta 1) that targets a cancer-specific antigen. The combination of scDb-hERG1-beta 1 with sub-optimal doses of Gemcitabine showed improved efficacy, low toxicity, and prolonged survival in a mouse model of PDAC. These findings suggest a potential novel approach to treat PDAC and other cancers by combining chemotherapy with ion channel modulators.
Article
Multidisciplinary Sciences
Takahiro Seimiya, Tatsunori Suzuki, Takuma Iwata, Takahiro Kishikawa, Kazuma Sekiba, Chikako Shibata, Kazunaga Ishigaki, Hiroaki Fujiwara, Hiroki Oyama, Sachiko Kanai, Tatsuya Sato, Yousuke Nakai, Rei Ishibashi, Masaru Moriyama, Ryo Nakagawa, Hideaki Ijichi, Motoyuki Otsuka, Kazuhiko Koike
Summary: Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose and has a poor prognosis. Human satellite II (HSATII) RNA, highly expressed in human PDAC, may serve as a biomarker for PDAC. We developed a convenient method, tandem repeat amplification by nuclease protection (TRAP) combined with droplet digital PCR (ddPCR), to measure serum HSATII RNA level with high sensitivity and reproducibility. By simultaneously measuring serum miR-21-5p level, we refined the method and constructed a PDAC-Index that accurately discriminates PDAC patients. The PDAC-Index was clinically validated as a supportive test in challenging diagnostic cases and showed satisfactory diagnostic performance for routine PDAC detection.
Article
Biochemistry & Molecular Biology
Jun Gong, Arsen Osipov, Jeremy Lorber, Mourad Tighiouart, Albert K. Kwan, Hayato Muranaka, Rasaq Akinsola, Sandrine Billet, Abrahm Levi, Anser Abbas, John Davelaar, Neil Bhowmick, Andrew E. Hendifar
Summary: Pancreatic cancer is difficult to treat with low survival rate. Glutamine supplementation has shown potential antitumor effects in combination with gemcitabine. The GlutaPanc phase I trial aims to investigate the safety of combining L-glutamine, gemcitabine, and nab-paclitaxel in pancreatic cancer patients. If successful, this combination could become a first-line systemic option for metastatic pancreatic cancer.
Article
Biochemistry & Molecular Biology
Ashwaq H. S. Yehya, Muhammad Asif, Amin M. S. Abdul Majid, Chern E. Oon
Summary: This study demonstrates that ethanolic extract of Orthosiphon stamineus sensitizes pancreatic cancer cells to gemcitabine by reducing multidrug-resistant proteins and molecules related to epithelial-mesenchymal transition. On the other hand, the combination of rosmarinic acid and gemcitabine did not show additional effects on cellular senescence or apoptosis.
BIOMEDICAL JOURNAL
(2021)
Article
Oncology
Manali Patki, Aishwarya Saraswat, Shraddha Bhutkar, Vikas Dukhande, Ketan Patel
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with Gemcitabine (Gem) as the main treatment, but its efficacy is limited by rapid inactivation by cytidine deaminase (CDA) in pancreatic cancer cells. A study found that a CDA inhibitor, Zebularine (Zeb), synergistically increased Gem-induced cytotoxicity in three pancreatic cancer cell lines. This combination treatment showed potential as a future approach for PDAC therapy.
EXPERIMENTAL CELL RESEARCH
(2021)