Posts Tagged ‘second’

Is the HPV vaccine necessary?

“I often have parents ask me if their child should get the HPV vaccine and what are my thoughts about giving it. Some parents are concerned it will promote sexual activity, others think it is unnecessary and others think their child is too young. If the child falls between the recommended ages given by the American Academy of Pediatrics I strongly recommend the vaccination. It really could be the difference between life and death,” said Hannah Chow-Johnson, MD, pediatrician at Loyola University Health System and assistant professor in the Department of Pediatrics at Loyola University Chicago Stritch School of Medicine.

According to Chow there are only two shots that can prevent cancer. One is hepatitis B and the other is the Human Papilloma Virus (HPV) vaccine. HPV is the most common sexually transmitted disease and is known to cause several different types of cancer, including cervical cancer, which is the second leading cancer-cause of death in women.

“Parents need to take into consideration the anti-cancer benefits when considering if they want their child to receive the HPV vaccine,” said Chow.

According to the Centers for Disease Control and Prevention there are more than 20 million people in the U.S. infected with HPV and at least half of these are between the ages of 15-25.

HPV is transmitted through intercourse and genital contact. Both men and women can harbor the virus, which can remain in a person for years after the initial infection.

“One of the scary aspects of HPV is that a person can be infected and not even know it. He or she may have no symptoms at all and still be spreading the virus,” Chow said. “This is why I strong believe in vaccinating males and females early, well before any exposure takes place.”

Prevention is critical when it comes to HPV. According to Chow the vaccine’s protection rate is 93 percent when given before any exposure. After exposure the vaccine doesn’t treat pre-exiting viruses but will help protect against future exposure.

“HPV is a very dangerous virus that can lead to death. Since there is no cure, prevention is all the more important. This vaccine could save the life of your child,” Chow said.

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Thunder God Vine, with assists by nanotechnology, could shake up future cancer treatment

Now a team of scientists, led by Prof. Taeghwan Hyeon at the Institute for Basic Science (IBS)/Seoul National University and Prof. Kam Man Hui at the National Cancer Center Singapore, has screened a library containing hundreds of natural products against a panel of HCC cells to search a better drug candidate. The screen uncovered a compound named triptolide, a traditional Chinese medicine isolated from the thunder god vine (Tripterygium wilfordii (Latin) or lei gong teng (Chinese)) which was found to be far more potent than current therapies. Studies from other researchers corroborate our findings as triptolide has also found to be very effective against several other malignant cancers including; pancreatic, neuroblastoma and cholangiocarcinoma. However this excitement was tempered when the drug was administered to mice as the increased potency was coupled with increased toxicity as well.

Maximizing potency, mitigating toxicity

Prof. Hyeon et al. endeavoured to alleviate the toxic burden by increasing the specific delivery of the drug to the tumor using a nanoformulation. The designed formulation was a pH-sensitive nanogel coated with the nucleotide precursor, folate. The researchers began by esterfying the polymer pluronic F127 with folate to make the coating material. They then polymerized β-benzyl-L-aspartate N-carboxy anhydride to make the core material pH-sensitive due to repulsive forces upon protonation under acidic conditions. “The combination of the two polymers forms a core/shell structured nanoparticle in water,” explains Prof. Hyeon. “We loaded triptolide into the hydrophobic core to produce a kind of drug-nanogel.”

A tumor model of folate-overexpressing HCC was then used to examine the effect of the nanogel formulation versus the free drug. As expected, the nanogel triptolide showed increased tumor accumulation and uptake into the tumor cells where the decreasing pH efficiently triggered release of the entrapped triptolide. The result was as hypothesized: In experiments on mice with HCC, the team found that its coated triptolide accumulated in the inflamed tumour tissues. Once there, the folate-targeted ligand enhances the HCC cells to take up the anticancer drug. Since the fluid inside tumour cells is more acidic (with a pH of around 6.8) compared to normal tissue (which has a pH of about 7.4), the drop in pH causes the coating to fall apart, and release the pure form of the triptolide, which then destroys the tumor cells, showing greater efficacy against the tumor and decrease the overall toxicity.

The mechanism of action of Nf-Trip-FR+ represents an auspicious therapeutic approach

While these initial proof-of-concept studies have been promising, many drugs fail to become an IND (Investigational New Drug); fewer still effectively replicate their results in human trials. However, a felicitous discovery occurred while the researchers were examining the mechanism of triptolide’s activity. Researchers at the National Cancer Center Singapore ran a profile on the effects triptolide had on protein expression in a variety of HCC cells. From this they learned triptolide primarily reduced the levels of two proteins, AURKA and CKS2, although the mechanism is still not known. The researchers then cross-checked these proteins against a clinical database of HCC patients and found an increased expression of these proteins correlates with the aggressiveness of the cancer. Thus it is hoped the negative effect triptolide has on these proteins could prove beneficial in terms of clinical outcomes when this drug finally becomes accepted for clinical studies in cancer patients.

The present work is detailed in ACS Nano.

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Cellular biology of colorectal cancer: New Insight

Lead author Kristi Neufeld, associate professor in the Department of Molecular Biosciences and co-leader of the Cancer Biology program at the KU Cancer Center, has spent the better part of her career trying to understand the various activities of APC, a protein whose functional loss is thought to initiate roughly 80 percent of all colon polyps, a precursor to colon cancer. Neufeld, along with her postdoctoral fellow Maged Zeineldin, undergraduate student Mathew Miller and veterinary pathologist Ruth Sullivan, now reports that APC found in a particular subcellular compartment, the nucleus, protects from inflammation as well as tumor development associated with chronic colitis.

Whether APC reaches the nucleus may well affect the ability of intestinal stem cells to produce differentiated cells with specialized functions, Neufeld said.

“It’s not widely appreciated, but there is still plenty of cell growth going on in adults, with the colon being a good example,” she said. “On average, we shed and replace about 70 pounds of intestinal tissue annually, so you can imagine that this process requires exquisite control to prevent tumor formation.”

Regular renewal of the colon lining occurs through stem cells that are capable of constantly dividing. These cells produce descendants that take up specific roles: By secreting mucin, for instance, goblet cells generate a mucus layer that serves as the colon’s physical barrier against its many microbial tenants. But if APC can’t find its way to the nucleus, Neufeld and her team have noted far fewer goblet cells as one outcome.

“We introduced a specific APC mutation into mice that took away the nuclear zip code, so to speak, leaving APC stuck in the cytoplasm,” Neufeld said. The researchers studied this mouse model under conditions that induce ulcerative colitis, a form of inflammatory bowel disease that can be a prelude to colon cancer.

Observing significantly more colon tumors in these mice compared to those with normal APC in the same disease setting, they hypothesized that functional nuclear APC might somehow guard against inflammation and its downstream effects, including tumor development. Now, Neufeld thinks she and her team may have a clue as to how this happens.

“The drop in goblet cell numbers we observed was striking,” she said. “We then examined one of the proteins found in mucus, called Muc2, and found that its RNA levels were greatly decreased. If there are fewer goblet cells as a result of APC being unable to reach the nucleus, there will also be less mucus, which could increase the colon’s sensitivity to bacteria and other microorganisms in the gut that are capable of promoting inflammation.”

Neufeld said while there are still no quick fixes for mutant genes, perhaps tools could be developed to synthetically replace this less-than-ideally thick mucus layer in affected people.

One known function of APC is that it halts cell proliferation: by muzzling the canonical arm of the Wnt signaling pathway, which otherwise instructs cells to go forth and multiply. Neufeld and her group have already shown, using the same mouse model, that APC stationed in the nucleus is necessary to suppress Wnt and its signaling partners — particularly β-catenin, a key target of normal APC. With a role for nuclear APC in controlling goblet cell differentiation now supported, the researchers are probing possible mechanisms to learn if and how Wnt pathway members might be involved.

Comprising 2,843 amino acids, APC is a large protein.

“Rather than being a simple, single-function protein, APC is more like a complex set of moving parts, each doing something different and most still poorly understood,” Neufeld said. “I think if the sole purpose of this protein was to target β-catenin for destruction, it wouldn’t need to be this large. Our next job is to figure out exactly how goblet cell differentiation is controlled by one or more of APC’s many components.”

Beyond a slew of mechanistic details, the bigger picture that Neufeld and her group will keep exploring is that some colon cancers could arise from an inflammatory response to bacterial penetration of a thinner-than-normal mucus layer in the gut, resulting from defective APC. The possibilities of just what APC does and doesn’t do, and how to compensate for any intestinal glitches related to loss of APC function, present a challenging mystery but also a plentiful harvest for scientists like Neufeld to reap going forward.

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