Abstract
Gold nanoshells combined with heat suggest future hope in breast cancer treatment
Delivering heat using gold nanoshells to breast tumor cells previously treated with radiation may kill cancer stem cells.
Researchers at The Methodist Hospital, TX, USA, Baylor College of Medicine, TX, USA and the University of Texas MD Anderson Cancer Centre, TX, USA, have developed a combination treatment, which may not only shrink tumors, but kill cancer stem cells.
The study utilized gold nanoshells to deliver a small amount of heat to breast cancer cells that had been previously treated with radiation. The application of a small amount of heat boosted the effectiveness of the treatment and demonstrated a dramatically decreased population of stem cancer cells.
Radiation therapy is known to decrease the size of a tumor; however, as Jeffrey Rosen, one of the researchers involved in the study, highlights, “We are focusing on the cancer stem cells, not just the shrinking of the tumor. Decreasing the size of the tumor is not a good end point. You can shrink the tumor with drugs or radiation, but it does not kill the stem cells”. Treating tumors with radiation often results in shrinking of the tumor, but leaves behind cells. A large percentage of these cells are cancer stem cells, which have the potential to regrow the tumor.
Once the cells have been treated with radiation, the gold nanoshells are introduced into the tumor and heated with a near-infrared laser. The gold nanoshells are able to move into the tumor through the blood vessels that provide the mass with nourishment. The nanoparticles are then heated specifically using the laser. The technique has been tested on highly resistant tumors in mice, Rosen states, “the advantage of the nanoshells is that you are not heating the whole mouse”.
The effect of the radiation treatment combined with the heated gold nanoshells not only shrank the tumor cells, but dramatically reduced the number of stubborn cancer stem cells. Rachel Atkinson, who led the study comments, “The cancer stem cells were more sensitive to the combination treatment than the bulk of the tumor. This is the exact opposite response we see with radiation only”. The research also revealed that the cancer cells could not repair the damage done to their DNA after the hyperthermia treatment, and the majority of cells died.
“The application of a small amount of heat boosted the effectiveness of the treatment and demonstrated a dramatically decreased population of stem cancer cells.”
The researchers are hopeful that the combination treatment may improve breast cancer treatment and survival rates, since they have the potential to eliminate cancer stem cells, as well as the bulk of the tumor. It is hoped that the progress the researchers have shown using the mouse models and xenographs may lead to clinical trials in patients.
Source: Atkinson RL, Zhang M, Diagaradjane P et al.: Thermal enhancement with optically activated gold nanoshells sensitizes breast cancer stem cells to radiation therapy. Sci. Transl. Med. 2(55), 55–79 (2010).
Scientists find a possible genetic link to severe morning sickness
In a recent study published in the American Journal of Obstetrics and Gynecology, scientists have found that the risk of hyperemis gravidarum (HG) could be genetic.
Hyperemis gravidarum is an extreme form of morning sickness, in which women experience nausea and severe vomiting, to the extent that food and liquid cannot be retained. Marlene Fejzo (David Geffen School of Medicine, University of California-Los Angeles, CA, USA) comments, “Pregnant women with a family history of extreme nausea in pregnancy should be aware that they may have it too, and healthcare providers should take a family history of nausea in pregnancy at the first visit with an obstetrician. The high familial prevalence strongly suggests a genetic component of this condition”.
Women diagnosed with HG and treated with intravenous fluids were requested to find a control – a friend who had not had HG and had a minimum of two pregnancies that lasted more than 27 weeks. Family history of severe nausea was compared in women with HG and the controls, and scientists found that it was more likely for women with HG to report having a sister suffering from severe morning sickness or HG, than the controls.
Authors found that “sisters of women with HG have a significantly increased risk of having HG themselves (odds ratio: 17.3; p = 0.005)”. They go on to say, “Cases have a significantly increased risk of having a mother with severe nausea and vomiting; 33% of cases reported an affected mother compared with 7.7% of controls (p < 0.0001)”.
Amongst the limiting factors of the study, identified by investigators was the possibility of misclassification due to ‘self-reports’ of family history. However, authors do conclude that, “There is a familial aggregation of HG. This study provides strong evidence for a genetic component to HG”. They explain that the cause of this pregnancy-related and ‘poorly understood’ disease could possibly be identified if the predisposing gene or genes are located.
Sources: Zhang Y, Cantor RM, Macgibbon K et al.: Familial aggregation of hyperemesis gravidarum. Am. J. Obstet. Gynecol. DOI: 10.1016/j.ajog.2010.09.018 (2010) (Epub ahead of print); UCLA Newsroom: newsroom.ucla.edu/portal/ucla/women-with-family-history-of-extreme-177990.aspx
Inhalable human papillomavirus vaccine may benefit developing countries
A dry powdered form of the human papillomavirus (HPV) vaccine that can be inhaled for targeted immunization against HPV may increase the availability and effectiveness of the vaccine to reduce cervical cancer. The research into the new form of the vaccine was announced at the 2010 International Pharmaceutical Federation (FIP) Pharmaceutical Sciences World Congress, in association with the American Association of Pharmaceutical Scientists Annual Meeting and Exposition.
HPV is currently the greatest cause of cervical cancer, the second biggest cause of female cancer mortality worldwide. Although the current adoption of the HPV vaccine is expected to reduce these numbers, 80% of deaths are in developing countries, and these countries may not have access to the vaccine.
The new form of the vaccine is said to be a powder that, when inhaled, is absorbed into the mucous-membrane of the respiratory tract. As HPV is also mucous-membrane based, this creates a more targeted antibody for the virus. The powdered form may also be more available for developing countries owing to it being more stable, less susceptible to contamination and easier to store and transport.
“While there are effective HPV vaccines on the market, cost, refrigeration and needle disposal shorten the reach they have”, commented lead researcher David McAdams from the University of Colorado at Boulder (CO, USA). “Our goal is to develop an economical, safe and easily administered HPV vaccine for everyone”.
Sources: CIRES research initiative: http://cires.colorado.edu/science/pro/irp/2010/sievers/; WHO Initiative for Vaccine Research: www.who.int/vaccine_research/diseases/hpv/en/
Screening of oncogene mutations in ovarian cancer cells could lead to effective personalized treatment
A technique known as OncoMap, which can be used to screen tumors for mutations in oncogenes, has been demonstrated to be able to identify new mutations present in ovarian cancer cells. It is hoped this will lead to personalized therapies targeted towards a specific mechanism in the tumor's biology, thus making individual treatments for ovarian cancer more effective.
The OncoMap technique uses mass spectrometry to detect the presence of point mutations, misspellings in DNA that can lead to cancerous cells, in over 100 known oncogenes present in advanced high-grade ovarian cancer cell.
The research, announced on the 17 November in the 22nd European Organisation for Research and Treatment of Cancer (EORTC)–NCI–American Association for Cancer Research (AACR) symposium on molecular targets and cancer therapeutics in Berlin, Germany, used OncoMap to identify mutations in genes such as KRAS, BRAF, CTNNB1 and PIK3CA, which were not previously identified as being present in cases of ovarian cancer.
The development of this technique could lead to personalized treatment for ovarian cancer, targeting specific mechanisms to reduce the growth of the cancer. It is hoped that screening of individual's tumors could lead to a growing database of mutations and tailored therapies known to be effective when they are present.
Targeting the treatment in this way is promising, as explained by the senior researcher, Ursula Matulonis, from the Dana Farber Cancer Institute in Boston (MA, USA): “We know that many human cancers have point mutations in certain oncogenes, and that these mutations can cause cancer cells to have a dependence on just one overactive gene or signaling pathway for the cancer cell's growth and survival – a phenomenon known as ‘oncogene addiction’. If the mutation that causes the oncogene addiction can be inhibited, then it seems that this often halts the cancer process. Examples of mutations that are successfully inhibited by targeted drugs are HER2 (for which trastuzumab is used in breast cancer), EGFR (erlotinib in lung cancer) and c-kit (imatinib in chronic myeloid leukaemia). So if we know the status of specific genes in a tumor, then this enables us to choose specific treatments that are likely to work successfully against the cancer.”
The researchers hope that it will not be long until we see OncoMap, and similar screening for oncogene mutations, being used in individual treatment programs for advanced ovarian cancer treatment.
Matulonis reported that trials in this process have already begun: “I have already referred several of our patients who are either newly diagnosed or have recurrent cancer, and who have mutations (one with KRAS and one with PIK3CA), to our phase I program for drugs studies specific to these mutations”.
Source: Eurek Alert, ECCO-the European CanCer Organisation press release: www.eurekalert.org/pub_releases/2010-11/eeco-rmt111510.php