KRAS, CDKN2A, SMAD4, and TP53 Gene Mutations Linked to Pancreatic Cancer Patient Survival Time

Alterations in four main genes are responsible for how long patients survive with pancreatic cancer, according to a new study.

via Pancreatic cancer survival linked to four genes — Pancreatic Cancer News — ScienceDaily

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The Medical Laboratory Scientist Personnel Shortage And The Future Of Lab Medicine

 

It was recently reported that the United States molecular diagnostics market is expected to exceed $9 billion by 2024 due to the increased incidence of infectious diseases and different types of cancer. In fact, there are at least 4 billion laboratory tests performed in the U.S. each year used to generate data on these diseases.

 

As this market continues to increase, so does the need for medical laboratory scientists. Correspondingly, there is a 22 percent projected growth of medical laboratory jobs that are needed to help physicians and patients detect and treat diseases faster. The United States’ population aged 65 and over will be comprised of around 83.7 million citizens in 2050. This increase in the aging population will lead to a greater need to diagnose medical conditions, such as cancer or type-2 diabetes, through laboratory procedures.

 

To learn more about the growing molecular diagnostics market and the future of medical laboratory science, check out the graphic below created by the University of Cincinnati.

 

MedicalLab-Scientist-Shortage-NEW

 

New Publication: Biobanking Weekly

 

Click here to visit Biobanking Weekly

The inaugural issue of Biobanking Weekly is coming to you just as the Global Biobank Week is closing providing leaders at the cutting edge of Biobanking to set the agenda for the months ahead. Important developments in biobanking this week include contributions to understanding of type 1 diabetes, the risks of 9/11 responders to fall victim to human papilloma virus (HPV) related head and neck cancers, new targets for osteoporosis treatment, advances in banking prostate cancer samples, the use of cystic fibrosis biobanks, the testing of drones for sample delivery, and the adoption of lean sigma six for efficient management and distribution of samples. Very exciting developments with plenty more forecast for the coming weeks.

Curcumin analogues extracted from Alpinia officinarum and Alnus japonica inhibited the FoxM1 signalling axis in a pancreatic cancer cell line

 

Alpinia officinarum or lesser galangal (高良姜), is a member of the ginger family, which originates from China and is now cultivated throughout Southeast Asia (Figure 1). The roots are known as galangal and are used in cooking, perfumes and are also known for their medicinal properties. Alnus japonica or East Asian alder (日本桤木), is a species of tree found in Japan, Korea, and eastern China, stretching to Russia. Diarylheptanoids, the family of which the anti-cancer agent curcumin from turmeric is a member, can be extracted from these plants. Diarylheptanoid compounds from these medicinal plants were found to inhibit the growth of the PANC-1 (KRAS heterozygous G12D, TP53 homozygous P72R and R273H) pancreatic cancer cell line [1, 2]. The mechanism was proposed to derive from inhibiting the FoxM1 transcription factor signalling axis.

 

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Figure 1: Alpinia officinarum. Credit: Biodiversity Heritage Library. No changes were made. Creative Commons Attribution 2.0 Generic (CC BY 2.0).

 

FoxM1 is a transcription factor of central importance to pancreatic cancer [3]. It promotes the transcription of genes involved in cell cycle progression and cell survival as well as migration and invasion [4]. FoxM1 transcription has been demonstrated to be promoted by the sonic hedgehog pathway in colorectal cancer and furthermore the hedgehog pathway is almost universally upregulated in pancreatic cancer [5, 6]. Dong et al. proposed that FoxM1 target genes are downregulated in response to the diarylheptanoid compounds due to Gli1/2 protein downregulation. Interestingly Stat3 signalling has been found to be downregulated by other diarylheptanoid compounds such as HO-3867 and Stat3 transcription can be indirectly upregulated by Gli1 via IL-6 [7, 8]. The extent to which different diarylheptanoid compounds could inhibit both FoxM1 and Stat3 axes in pancreatic cancer  is an open question.  

 

Refs

  1. Dong GZ, Jeong JH, Lee YI, Lee SY, Zhao HY, Jeon R, Lee HJ, Ryu JH. Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway. Arch Pharm Res. 2017 Apr;40(4):509-517. Doi: 10.1007/s12272-017-0905-2. PubMed PMID: 28258481.
  2. Gradiz R, Silva HC, Carvalho L, Botelho MF, Mota-Pinto A. MIA PaCa-2 and PANC-1 – pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors. Sci Rep. 2016 Feb 17;6:21648. Doi: 10.1038/srep21648. PubMed PMID: 26884312.
  3. Akbari B, Mohammadnia A, Yaqubi M, Wee P, Mahdiuni H. Comprehensive Dissection of Transcriptome Data and Regulatory Factors in Pancreatic Cancer Cells. J Cell Biochem. 2017 Apr 12. doi: 10.1002/jcb.26053. PubMed PMID: 28401644.
  4. Quan M, Wang P, Cui J, Gao Y, Xie K. The roles of FOXM1 in pancreatic stem cells and carcinogenesis. Mol Cancer. 2013 Dec 10;12:159. Doi: 10.1186/1476-4598-12-159. Review. PubMed PMID: 24325450.
  5. Wang D, Hu G, Du Y, Zhang C, Lu Q, Lv N, Luo S. Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells. J Exp Clin Cancer Res. 2017 Feb 2;36(1):23. doi: 10.1186/s13046-017-0491-7. PubMed PMID: 28148279.
  6. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu B, Lin MT, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26;321(5897):1801-6. Doi: 10.1126/science.1164368. PubMed PMID: 18772397.
  7. Hu Y, Zhao C, Zheng H, Lu K, Shi D, Liu Z, Dai X, Zhang Y, Zhang X, Hu W, Liang G. A novel STAT3 inhibitor HO-3867 induces cell apoptosis by reactive oxygen species-dependent endoplasmic reticulum stress in human pancreatic cancer cells. Anticancer Drugs. 2017 Apr;28(4):392-400. Doi: 10.1097/CAD.0000000000000470. PubMed PMID: 28067673.
  8. Mills LD, Zhang Y, Marler RJ, Herreros-Villanueva M, Zhang L, Almada LL, Couch F, Wetmore C, Pasca di Magliano M, Fernandez-Zapico ME. Loss of the transcription factor GLI1 identifies a signaling network in the tumor microenvironment mediating KRAS oncogene-induced transformation. J Biol Chem. 2013 Apr 26;288(17):11786-94. doi: 10.1074/jbc.M112.438846. PubMed PMID:23482563.

 

 

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Journal Publications:

  1. Orchard-Webb D. 2016. Progress Toward Commercial Scale and Efficiency in Cell Therapy Bioprocessing. BioProcess International. October Supplement. http://www.bioprocessintl.com/manufacturing/cell-therapies/manufacturing-cell-therapies-commercial-scale-efficiency/
  1. Orchard-Webb D. 2015. Future Directions in Pancreatic Cancer Therapy. JOP. Journal of the Pancreas 16:249-255.
  1. Orchard-Webb D.J., Lee T.C., Cook G.P., Blair G.E. 2014. CUB Domain Containing Protein 1 (CDCP1) modulates adhesion and motility in colon cancer cells. BMC Cancer. 14:754.
  1. Orchard-Webb D; Fox N; Elghazawy RM; Speirs V; Smith AM; Lodge JPA; Melcher AA; Verbeke CS; Blair GE. 2012. Development of a Chimaeric Oncolytic Adenovirus Vector for Pancreatic Cancer Biotherapy. Journal of pathology. 228: S18-S18.
  1. Elghazawy RM; Fox N; Orchard-Webb D; Speirs V; Smith AM; Lodge JPA; Verbeke CS; Blair GE. 2012. An Ex-Vivo Model of Human Pancreatic Cancer. Journal of pathology. 228: S19-S19.
  1. Orchard-Webb, D. 2011. The cancer cell biology of the integral membrane protein CUB domain containing protein 1 (CDCP1). University of Leeds. Thesis.
  1. Orchard-Webb, D. J., Cook, G. P., and Blair, G. E. 2010. Poster 482: Characterising the role of the metastasis associated cell surface glycoprotein CDCP1 in cancer cell lines – possible roles in cell adhesion and survival. EJC Supplements 8: 123.
  1. Fini, M.A., Orchard-Webb, D., Kosmider, B., Amon, J.D., Kelland, R., Shibao, G., and Wright, R.M. 2008. Migratory Activity of Human Breast Cancer Cells is Modulated by Differential Expression of Xanthine Oxidoreductase.  J. Cell. Biochem.  105: 1008-1026.

 

Web Publications:

  1. Orchard-Webb D. 2014. Next generation treatments for type I diabetes. http://www.apptheneum.com/next-generation-treatments-type-diabetes/

 

Editing:

  1. Niebuhr M., Scharonow H., Gathmann M., Mamerow D., Werfel T. 2010. Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis. J Allergy Clin Immunol. 126: 1176-1183.e4. http://www.jacionline.org/article/S0091-6749(10)01264-9/abstract

 

David Orchard-Webb, PhD
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Resource – STAT3 – Pancreatic Cancer

 

STAT3 plays a pivotal role in pancreatic cancer and is drawing increased attention as a potential drug target for the disease. This post will be updated periodically.

 

STAT3 inhibitorsRefs

MIR506 – Sun L, Hu L, Cogdell D, Lu L, Gao C, Tian W, Zhang Z, Kang Y, Fleming JB, Zhang W. MIR506 induces autophagy-related cell death in pancreatic cancer cells by targeting the STAT3 pathway. Autophagy. 2017 Jan 25:0. doi: 10.1080/15548627.2017.1280217. PubMed PMID: 28121485.

HO-3867

Nexrutine®

Renalase

AM0010

AZD9150 – AZD9150 With MEDI4736 in Patients With Advanced Pancreatic, Non-Small Lung and Colorectal Cancer. ClinicalTrials.gov Identifier: NCT02983578