The ribosome inhibiting protein riproximin shows antineoplastic activity in experimental pancreatic cancer liver metastasis

Sex disparity in cancer is so far inadequately considered, and components of its basis are rather unknown. We reveal that male versus female pancreatic cancer (PC) patients and mice show shortened survival, more frequent liver metastasis, and elevated hepatic metastasis-promoting gene expression. Tissue inhibitor of metalloproteinases 1 (TIMP1) was the secreted factor with the strongest male-biased expression in patient-derived pancreatic tumors. Male-specific up-regulation of systemic TIMP1 was demonstrated in PC mouse models and patients. Using TIMP1-competent and TIMP1-deficient PC mouse models, we established a causal role of TIMP1 in determining shortened survival and increased liver metastasis in males. Observing TIMP1 expression as a risk parameter in males led to identification of a subpopulation exhibiting increased TIMP1 levels (T1HI males) in both primary tumors and blood. T1HI males showed increased risk for liver metastasis development not only in PC but also in colorectal cancer and melanoma. This study reveals a lifestyle-independent sex disparity in liver metastasis and may open new avenues toward precision medicine.

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LAMA4 upregulation is associated with high liver metastasis potential and poor survival outcome of Pancreatic Cancer: Erratum

Theranostics ◽

10.7150/thno.68023 ◽

2021 ◽

Vol 11 (20) ◽

pp. 10171-10172

Author(s):

Biao Zheng ◽

Jianhua Qu ◽

Kenoki Ohuchida ◽

Haimin Feng ◽

Stephen Jun Fei Chong ◽

...

Keyword(s):

Pancreatic Cancer ◽

Liver Metastasis ◽

Survival Outcome ◽

Poor Survival ◽

Poor Survival Outcome ◽

High Liver

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DNA Ploidy and Markovian Analysis of Neoplastic Progression in Experimental Pancreatic Cancer

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215540305100305 ◽

2003 ◽

Vol 51 (3) ◽

pp. 303-309 ◽

Cited By ~ 16

Author(s):

Russell G. Postier ◽

Megan R. Lerner ◽

Stan A. Lightfoot ◽

Rick Vannarath ◽

Mary M. Lane ◽

...

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Adenocarcinoma ◽

Dna Ploidy ◽

Computer Assisted ◽

Nuclear Morphology ◽

Neoplastic Progression ◽

Atypical Cell ◽

Atypical Cells ◽

Experimental Pancreatic Cancer ◽

Markovian Analysis

Computer-assisted analysis of DNA ploidy and nuclear morphology were used to elucidate changes in the cell nucleus that occur during the development of experimental pancreatic cancer. Ductal pancreatic adenocarcinoma was induced in 49 Syrian hamsters by SC injection of N-nitrosobis (2-oxopropyl) amine; twenty hamsters served as controls. Groups of animals were sacrificed every 4 weeks for 20 weeks and adjacent sections of pancreatic tissue were H&E and Feulgen-stained for light microscopy and computer assisted cytometry. Pancreatic ductal cells were classified as normal, atypical, or malignant; tissue inflammation (pancreatitis) was also noted when present. DNA ploidy and nuclear morphology evaluation (Markovian analysis) identified an atypical cell stage clearly distinguishable from either normal or malignant cells; pancreatitis preceded this atypia. The DNA ploidy histogram of these atypical cells revealed a major diploid peak and a minor aneuploid peak. The receiver operator characteristic curve areas for a logistic regression model of normal vs atypical cells was 0.94 and for atypical vs malignant was 0.98, numbers indicative of near-perfect discrimination among these three cell types. The ability to identify an atypical cell population should be useful in establishing the role of these cells in the progression of human pancreatic adenocarcinoma.

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Experimental pancreatic cancer in the rat treated by photodynamic therapy

British Journal of Surgery ◽

10.1002/bjs.1800810835 ◽

1994 ◽

Vol 81 (8) ◽

pp. 1185-1189 ◽

Cited By ~ 21

Author(s):

S. Evrard ◽

P. Keller ◽

A. Hajri ◽

G. Balboni ◽

L. Mendoza-Burgos ◽

...

Keyword(s):

Pancreatic Cancer ◽

Photodynamic Therapy ◽

Experimental Pancreatic Cancer

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Survival benefit of KRN7000 immune therapy in combination with TNP470 in hamster liver metastasis model of pancreatic cancer

Oncology Reports ◽

10.3892/or.10.5.1201 ◽

2003 ◽

Author(s):

Gaku Matsumoto ◽

Shigenori Nagai ◽

Mariko Muta ◽

Koji Tsuruta ◽

Atsutake Okamoto ◽

...

Keyword(s):

Pancreatic Cancer ◽

Liver Metastasis ◽

Survival Benefit ◽

Immune Therapy ◽

Metastasis Model

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A Phase I/Ib trial of Ad-REIC in liver cancer: study protocol

Future Oncology ◽

10.2217/fon-2019-0115 ◽

2019 ◽

Vol 15 (31) ◽

pp. 3547-3554 ◽

Cited By ~ 1

Author(s):

Astushi Oyama ◽

Hidenori Shiraha ◽

Daisuke Uchida ◽

Masaya Iwamuro ◽

Hironari Kato ◽

...

Keyword(s):

Pancreatic Cancer ◽

Liver Metastasis ◽

Phase I ◽

Liver Tumor ◽

Objective Response ◽

University Hospital ◽

Open Label ◽

Safety And Efficacy ◽

Immortalized Cells ◽

Dose Limiting Toxicity

This study will assess the safety and efficacy of the administration of adenoviral vector expressing the human-reduced expression in immortalized cells (Ad-REIC) to a liver tumor in patients with hepatocellular carcinoma (HCC) or liver metastasis of pancreatic cancer. A Phase I clinical study of Ad-REIC administration to a liver tumor in a patient with HCC or liver metastasis of pancreatic cancer will be conducted. The study is a single-arm, prospective, nonrandomized, noncomparative, open-label, single-center trial performed in Okayama University Hospital, Okayama, Japan. Ad-REIC will be injected into the liver tumor under ultrasound guidance. Ad-REIC administration will be repeated a total of three-times every 2 weeks. The primary end point is the dose-limiting toxicity and incidence of adverse events. The secondary end points are the objective response rate and disease control rate. This study aims to expand the indication of Ad-REIC by assessing its safety and efficacy in patients with HCC or liver metastasis of pancreatic cancer.

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