Significant growth inhibition of orthotopic pancreatic ductal adenocarcinoma by CpG oligonucleotides in immunodeficient mice

Tepel, Juergen; Dagvadorj, O.; Kapischke, Matthias; Sipos, Bence; Leins, A.; Kremer, Bernd; Kalthoff, Holger

doi:10.1007/s00384-005-0013-5

Cited by 7 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are important and relevant features common to infection with S pyogenes in mice and human infection: (1) rapid cell damage after infection, accompanied by ulceration and necrosis of the infected tissue; (2) significant and sustained elevation of proinflammatory cytokines (TNFα, IFNγ) and chemokines (G-CSF); (3) high influx of inflammatory cells of the innate immune system (eg, neutrophils, macrophages and NK cells) into the focus of infection; and (4) activation of an adaptive, cell-mediated immune response 16 33 – 35. Moreover, intravenous administration of live bacteria causes severe toxicity 25 36.…”

Section: Discussionmentioning

confidence: 99%

“…Given the dismal prognosis for patients with ductal adenocarcinoma of the pancreas,1 12 novel immunotherapeutic intervention possibilities must be developed to treat this malignancy 4 13 – 16 . Streptococcus pyogenes is an important facultative anaerobic pathogen that can cause infections of varying severity in humans, ranging from simple, non-suppurative infections of the pharynx and skin to life-threatening invasive infections 17.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model

Maletzki

Linnebacher

Kreikemeyer

et al. 2007

Gut

View full text Add to dashboard Cite

We provide data that both the direct lytic activity of S pyogenes towards tumour cells and the infection-driven infiltration of tumours by cells of the innate immune system lead to damage of tumour cells followed by a dissemination of tumour components. This last outcome allows for the activation of tumour-specific effector cells, most probably in draining lymph nodes, promoted by the proinflammatory context. Taken together, these data indicate that the application of live S pyogenes may be a promising new treatment strategy for advanced pancreatic cancer patients that warrants further investigation.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model

Maletzki

Linnebacher

Kreikemeyer

et al. 2007

Gut

View full text Add to dashboard Cite

show abstract

“…The orthotopic injection was performed as previously described [82]. Human metastatic pancreas adenocarcinoma cells Colo357 were detached with Accutase solution (PAA Laboratories GmbH), resuspended at the concentration of 10 6 cells ml −1 in 25 μl of Matrigel (BD-Biosciences) and stored on ice.…”

Section: Methodsmentioning

confidence: 99%

Tumor-reducing effect of the clinically used drug clofazimine in a SCID mouse model of pancreatic ductal adenocarcinoma

Zaccagnino¹,

Managò

Leanza

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) represents the most common form of pancreatic cancer with rising incidence in developing countries. Unfortunately, the overall 5-year survival rate is still less than 5%. The most frequent oncogenic mutations in PDAC are loss-of function mutations in p53 and gain-of-function mutations in KRAS. Here we show that clofazimine (Lamprene), a drug already used in the clinic for autoimmune diseases and leprosy, is able to efficiently kill in vitro five different PDAC cell lines harboring p53 mutations. We provide evidence that clofazimine induces apoptosis in PDAC cells with an EC50 in the μM range via its specific inhibitory action on the potassium channel Kv1.3. Intraperitoneal injection of clofazimine resulted in its accumulation in the pancreas of mice 8 hours after administration. Using an orthotopic PDAC xenotransplantation model in SCID beige mouse, we show that clofazimine significantly and strongly reduced the primary tumor weight. Thus, our work identifies clofazimine as a promising therapeutic agent against PDAC and further highlights ion channels as possible oncological targets.

show abstract

“…Volume was determined as the product of length, width and height. For the PDAC model, the orthotopic injection was performed as previously described (Tepel et al, 2006). In detail, human metastatic pancreas adenocarcinoma cells Colo357 were detached with Accutase solution (Healthcare, Little Chalfont, UK), resuspended at the concentration of 6 cells/mL in 25 mL of Matrigel (BD-Biosciences, Heidelberg, Germany) and stored on ice.…”

Section: In Vivo Experiments and Immunohistochemistrymentioning

confidence: 99%

Direct Pharmacological Targeting of a Mitochondrial Ion Channel Selectively Kills Tumor Cells In Vivo

et al. 2017

View full text Add to dashboard Cite

The potassium channel Kv1.3 is highly expressed in the mitochondria of various cancerous cells. Here we show that direct inhibition of Kv1.3 using two mitochondria-targeted inhibitors alters mitochondrial function and leads to reactive oxygen species (ROS)-mediated death of even chemoresistant cells independently of p53 status. These inhibitors killed 98% of ex vivo primary chronic B-lymphocytic leukemia tumor cells while sparing healthy B cells. In orthotopic mouse models of melanoma and pancreatic ductal adenocarcinoma, the compounds reduced tumor size by more than 90% and 60%, respectively, while sparing immune and cardiac functions. Our work provides direct evidence that specific pharmacological targeting of a mitochondrial potassium channel can lead to ROS-mediated selective apoptosis of cancer cells in vivo, without causing significant side effects.

show abstract

Significant growth inhibition of orthotopic pancreatic ductal adenocarcinoma by CpG oligonucleotides in immunodeficient mice

Abstract: CpG-1826 induces significant growth-inhibitory effects on orthotopic xenotransplanted pancreatic tumours in highly immunodeficient mice, which might be explained by innate immunity mechanisms and possibly a complex interaction of tumour and stroma cells.

Cited by 7 publications

References 30 publications

Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model

Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model

Tumor-reducing effect of the clinically used drug clofazimine in a SCID mouse model of pancreatic ductal adenocarcinoma

Direct Pharmacological Targeting of a Mitochondrial Ion Channel Selectively Kills Tumor Cells In Vivo

Contact Info

Product

Resources

About