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Metastasis Occurring in Pancreatic Cancer

Submitted by jgirgis on Thu, 03/23/2017 - 19:58

Pancreatic ductal adenocarcinoma (PDAC) is a cancer that quickly turns metastatic, which is why PDAC has a 5% survival rate.  Because of this, PDAC is the 4th most common cause of cancer-related death. PDAC metastasis is considered advanced when it has metastasized to distant locations such as the lungs, bone, brain, etc. In PDAC patients, hypoxia always occurs. Hypoxia means low oxygen. Hypoxia is related to metastasis because it activates tumor progression, malignancy, and resistance to therapy. Hypoxia-inducible factors (HIFs) facilitate hypoxia. Oncogenes or tumor suppressors that are inactive activate HIFs. In PDAC, a major regulator of hypoxia is inducible factor-1 (HIF-1). In addition, in PDAC patients that display hypoxia there is a single nucleotide polymorphism (SNP) that occurs at HIF-1 G1790A and C1772T. It was discovered that patients that had these SNPs had an increased risk of metastasis occurring faster.



Pancreatic Cancer: Metastasis

Submitted by jgirgis on Thu, 03/23/2017 - 18:41

Pancreatic ductal adenocarcinoma (PDAC) is a cancer that quickly turns to metastatic. PDAC metastasis is considered advanced when it has metastasized to distant locations such as the lungs, bone, brain, etc. In PDAC, hypoxia occurs. Hypoxia is low oxygen and activates tumor progression, malignancy, and resistance to therapy. Hypoxia signaling is mediated by the hypoxia-inducible factors (HIFs). HIFs are activated by oncogenes or tumor suppressors that are inactive. In PDAC, a major regulator of hypoxia is inducible factor-1 (HIF-1). In addition, in PDAC, there is a single nucleotide polymorphism (SNP) that occurs at HIF-1 G1790A and C1772T. It was found that patients that these SNP’s had an increased risk of metastasis occurring quickly with PDAC. Also, the G1790A SNP was correlated with a higher expression of HIF-1, which regulates metastasis progression.

Not only does HIF-1 contribute to the regulation of metastasis in patients with PDAC, but there is an actin-bundling protein that is called fascin. Fascin is overexpressed in patients with PDAC and this overexpression causes the upregulation of metastasis occurring in PDAC patients. HIF-1 relates to fascin because it directly activates the expression of fascin.  There is another actin-bundling protein that is called LASP-1 (LIM and SH3 protein 1). This is also overexpressed in patients with PDAC due to HIF-1. The combination of the overexpression of fascin and LASP-1 cause metastasis to occur quickly in patients with PDAC.  The way that HIF-1 is activates is through a phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathway.



Observing the Sunset

Submitted by jgirgis on Wed, 03/22/2017 - 23:22

The sunset yesterday consisted of a mixture of purple, orange, yellow, and pink colors. I was watching the sunset next to the field near the honors college. The grass on the field was very dark. One could not even make out that it was grass if they did not know that it was a field. At this time when one looked out at the field, one could see the sunset very clearly. The bottom of the sunset was orange and yellow, which was the sun glowing. The middle of the sun was a very bright yellow color. Right above the sun was an orange color that spread across the horizon on the field. There were not many clouds on the horizon. However, after the orange color, the clouds appeared. The clouds were a very dark purple. When one looked closely, the clouds were such a dark color that they could be perceived as black. The clouds were also very voluminous. The clouds seemed very bouncy and full, although they were a dark color. In addition to the clouds being dark, in between the clouds and the orange horizon, there was a faint pink color. There were not any clouds on the parts of the sunset that were pink. The pink was a very light pink color, making this sunset very special.

Metastasis in Cancer

Submitted by jgirgis on Thu, 03/09/2017 - 21:44

There are many systems involved with metastasis in cancer. One of many is the EMT system. This system is the epithelial-mesenchymal transitions, which is a process when epithelial cells acquire mesenchymal properties. This means fibroblast properties and an increase in motility.  Cancerous cells enter the blood stream during this transition phase and metastasis occurs. The process of the EMT system is that first cancer cells from the primary tumor invade the local tissue and invade nearby microvessels by entering the circulation. After, tumor cells are trapped in the microvessels of distant tissues, where they leave the bloodstream by extravasation. The final step is the acquired ability of micrometastic deposits to form macroscopic metastes, which is colonization.

Another system is the process of angiogenesis. This is the process of creating new blood vessels. This process involves the migration, growth, and differentiation of endothelial cells.  This stands for bone marrow cells. It secretes GRN, which is growth factor granulin. The process involves CD11b+/Gr1+  myeloid cells that were found to facilitate tumour-assocoated angiogenesis and to render tumours refractory to inhibitions by anti-VEGF treatment. In addition, through bone marrow cells (BMCs), vascular endothelial growth factor-A and placental growth factor trigger the release of BMCs from the bone marrow into the circulation. Cancer-associated fibroblasts are abundant in most carcinomas and are linked to tumour angiogenesis. For example, in breast cancer, cancer-associated fibroblasts release CXCL12 into the blood stream in people affected by breast cancer. CXCL12 releases progenitor cells into the circulation, which results in TME gathering and then promotion of angiogenesis. Platelets at as a long-range delivery system between aggressively growing tumours and tumors that are in a far distance. When VEGFR2+ BMCc and cytokines are taken up by platelets, then angiogenesis is promoted at metastatic sites. Some important cytokines that are involved with angiogenesis at metastatic sites are VEGF, TGF-beta1, PDGF-BB, PIGF, IL-6, and CXCL1. The platelets take up these factors

Another process of metastasis involves affecting BMCs. BMCs are bone marrow cells. When bone marrow cells secrete GRN, a CAF phenotype is adopted. CAF is a cancer-associated fibroblast, leading to expression of pro-inflammatory and matrix remodeling genes and upregulation of GFF15. It also promotes recruitment of circulating inflammatory cells to the tumor site, which results in tumor progression (metastasis).

Manipulation of the extravasation state in the EMT system would help stop metastasis. If extravasation is stopped, then tumor cells would not be able to escape circulation, which would stop metastasis.  In addition, if cancer-associated fibroblasts of angiogensis are stopped and are not able to release CXCL12 into the bloodstream, then progenitor cells would not be released into the circulation. Therefore the promotion of angiogenesis in metastatic tumors would not occur. In addition, with bone marrow cells, halting cancer-associated fibroblasts would stop tumor progression (metastasis) because the expression of pro-inflammatory genes and the recruitment of circulating inflammatory cells would not occur.



Geese at the Campus Pond

Submitted by jgirgis on Thu, 03/09/2017 - 21:34

           This afternoon, I visited the campus pond to observe the animals that were inside or around the pond near the library. Geese were predominantly in the pond swimming in it. The first observation that was made regarding the geese was that they had beige backs, and their feathers were located on their backs. Their feathers were a mixture of white and beige. The second observation that was noted was that the geese had white bottoms, yet their heads and necks were all black. The next set of observations I made did not involve the geese’s physical appearance, yet was about their behavior. Most of the geese were sitting in the pond, swimming quietly. One could barely hear the geese glide along the water. There were only three instances where a goose would start flapping its wings along the water and start screeching. This alarmed other geese, which started a chain reaction of screeching. However, this only lasted a few seconds.

Geese on Pond

Submitted by jgirgis on Wed, 03/08/2017 - 23:38

           This afternoon, I went to the campus pond to observe the animals around or on the pond. The animal that I greatly noticed was a goose. The goose had a beige back and feathers. The feathers were mostly beige, but also had some white on them. The bottom of the goose was white. The goose’s head and neck were black. However, there was a strip on the head that was white. The nose and the eyes of the goose were also black.

            There were many geese swimming on the pond. Some geese were swimming very fast around the pond and around other geese. Those geese that were swimming fast would sometimes use their wings to get a few feet off of the pond and then return back to their spot. When they would open their wings and use it, the geese would make a screech. Other geese were very quiet and would just sit in the water. Those geese would not really move unless another goose started screeching that was nearby it. When one goose would screech and call out, then another goose would screech out as well. They would start communicating with each other and many geese would join in, flapping their wings as well. In addition, sometimes the geese would dunk their head underwater and extend their heads.

Drosophila Crosses

Submitted by jgirgis on Tue, 03/07/2017 - 22:06

In my biology 486H laboratory class, we set up 25 “single-male” crosses of drosophila. Each one would had one male and 5 virgin females in a vial. We used a transponase to mobilize a Gal4 driver to new areas of the genome. The purpose of this was to generate new Gal4 tools so that they are expressed in different patterns. These patterns would be tested in future experiments.

We received one vial of 25 males with the genotype, PB{Gal4,w+}/Y; +CyO, P[TPase]; +/+. After this, we received 5 vials that contained 25 virgin females each. I received females with the genotype yw; P[UAS-GFP, w+]; + on chromosome 2. One observation after receiving these vials were that the males had orange eyes and the females had red eyes. The males carry Gal4 on the X chromosome. This was made by first cloning Gal4 intro a transposon called Piggybac, and then injecting the PB {Gal4, w+} DNA construct into eggs, along with the Piggybac transposase “TPase”. TPase specifically recognizes the Piggyback transposon and randomly integrates it into genomic DNA.  The males carry TPase on one copy of their second chromosome. This particular copy of the second chromosome is special in that it contains many inversions. It has all the same genes as a normal second chromosome in flies, but in a different order.

To set up the crosses, we put the females asleep from one vial and assigned 5 females into each vial. In total, we had 25 vials. After putting 5 virgin females into vials, then one male was put into each of the 25 vials.

In future experiments, the results will be observed to look for enhancer patterns.

Moss Research Proposal Idea

Submitted by jgirgis on Fri, 03/03/2017 - 11:01

I discovered a research paper that discusses the effects of microwave frequency electromagnetic radiation on plants such as anethum graveloens, otherwise known as dill. The methods consisted of observing dill that grew in normal conditions without exposure to microwave frequency electromagnetic radiation and then observing dill that grew in conditions with exposure to microwave frequency electromagnetic radiation. The results were that there was a decrease in the size of the organelles for the dill that was exposed to microwave frequency electromagnetic radiation compared to the controlled dill. This experiment could be applied to moss, and instead of using microwave frequency electromagnetic radiation, one could utilize cellular frequency electromagnetic radiation. This way, one could assess if cellular devices halt the growth of moss compared to moss that are not exposed to cellular or microwave frequency electromagnetic radiation.

Soran M-L, Stan M, Niinemets Ü, Copolovici L. Influence of microwave frequency electromagnetic radiation on terpene emission and content in aromatic plants. Journal of plant physiology. 2014 Sep 15 [accessed 2017 Mar 3].

Observing Roses and Tulips

Submitted by jgirgis on Fri, 03/03/2017 - 10:46

        The flowers that are in my house consist of roses and tulips. The colors of the roses are red and white. The red roses started blooming, as its petals started separating from the center. On the other hand, the white roses have not started blooming at all, as the petals have not started separating. Instead, they are tightly bunched together in the center. Both the red and white roses have long green stems. The part of the stem closest to the flower is a lighter green, while the part farthest from the flower is a darker green.

        Not only are there roses, but there are tulips in the bouquet that are red and yellow. Both colors have started fully blooming, as their petals started moving away from the center, similar to the red roses. Each tulip has six petals. The center of both tulips is a bright, yellow color. The anther of the tulips is a dark, chocolate brown color. The anther has little bits that have started falling. The texture of the anther is extremely soft. The style and stigma of the tulips are a light yellow and green color with a thicker texture compared to the anther.

Pancreatic Cancer

Submitted by jgirgis on Fri, 03/03/2017 - 09:30
Pancreatic cancer is one of the most aggressive forms of cancer, which develops in the tissues of the pancreas, an organ involved in blood sugar control, metabolism, and digestion. Pancreatic cancer is the 3rd leading cause of cancer-related death in the United States, and is expected to be the 2nd leading cause of cancer-related death by 2020 (Szalay, 2015). 91% of people diagnosed with pancreatic cancer pass away within five years of diagnosis, primarily because this form of cancer is often difficult to detect in the early stages, and tends to have already metastasized by the time of detection (Szalay, 2015). 

The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). This form of pancreatic cancer accounts for about 85% of cases and in most situations, when pancreatic cancer is referred to, pancreatic adenocarcinoma is assumed. Because the pancreas aids in digestion, people afflicted with this form of cancer can experience issues with their digestion in addition to the deadly impact of the tumors and tissue mutation/degradation associated with all cancer. The gastrointestinal symptoms experienced by PDAC patients are often what lead to the discovery and diagnosis of pancreatic cancer.

Pancreatic ductal adenocarcinoma is characterized by several signature mutations which differentiate it from other subtypes of pancreatic cancer. Expression of KRAS2 and AKT2 oncogenes allow for unrestricted activation of growth pathways in these cells. KRAS2 is found to be overexpressed in 90%-95% of pancreatic cancer cases while AKT2 is more specific and is only found in 10%-15% of pancreatic cancers (Maitra, 2007). KRAS2 is an essential cell growth and survival gene that encodes for GTP binding proteins. 

In addition to unrestricted activation of growth pathways, PDAC cells also thrive by inactivating cell death pathways. The most commonly inactivated cell death pathway in pancreatic cancer cells is the p16/CDKN2A pathway. In healthy cells, the p16/CDKN2A pathway codes for a CDK inhibitor that prevents progression through the G1-S cell cycle checkpoint (Maitra, 2007). The p16/CDKN2A pathway is inactive in 90% of pancreatic cancers, allowing the PDAC cells to grow and divide sans regulation. A less prevalent cell death pathway mutated in 50%-75% of pancreatic cancers is one that inactivates the TP53. TP53 codes for the P53 protein which is involved in regulation of apoptosis and cell cycle checkpoint progression (Maitra, 2007).


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