The study, published in the International Journal of Cancer, focuses on a gene originally cloned in the laboratory of primary investigator Paul B. Fisher, M.Ph., Ph.D. The gene, melanoma differentiation associated gene-7 (mda-7), also known as interleukin (IL)-24, has been shown to directly impact two forms of cell suicide known as apoptosis and toxic autophagy, regulate the development of new blood vessels and also play a role in promoting cancer cell destruction by the immune system. In the present study, the researchers used a recombinant adenovirus vector, an engineered virus with modified genetic material, known as Ad.mda-7 to deliver the mda-7/IL-24 gene with its encoded protein directly to the tumor.

“Therapy with the mda-7/IL-24 gene has been shown to be safe in a phase I/II clinical trial involving patients with advanced cancers, and prior studies in my laboratory and with collaborators have shown that the gene could also be effective against breast, prostate, lung, colorectal, ovarian, pancreatic and brain cancers,” says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics program at VCU Massey, chairman of VCU School of Medicine’s Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine (VIMM). “Our study demonstrates that this therapy could be an effective way to eradicate both early and advanced stage breast cancer, and could even be used as a preventative therapy to reduce the risk of cancer recurrence.”

The researchers found that infection of human breast cancer cells with the adenovirus decreased the proliferation of breast cancer stem cells without affecting normal breast stem cells. It was also shown to induce a stress response in the cells that led to apoptosis by disrupting Wnt/B-catenin signaling, a process cells rely upon to transmit signals that initiate biological functions critical to survival. In mouse models, the therapy profoundly inhibited the growth of tumors generated from breast cancer stem cells and also killed cancer cells in distant, uninjected tumors.

Since discovering the mda-7/IL-24 gene, Fisher and his team have worked to develop better ways to deliver it to cancer cells, including two cancer “terminator” viruses known as Ad.5-CTV and Ad.5/3-CTV. Cancer terminator viruses are unique because they are designed to replicate only within cancer cells while delivering immune-modulating and toxic genes such as MDA-7/IL-24. Coupled with a novel stealth delivery technique known as ultrasound-targeted microbubble destruction (UTMD), researchers can now systemically deliver viruses and therapeutic genes and proteins directly to tumors and their surrounding tissue (microenvironment) at both primary and metastatic tumor sites. UTMD uses microscopic, gas-filled bubbles that can be paired with viral therapies, therapeutic genes and proteins, and imaging agents and can then be released in a site and target-specific manner via ultrasound. Fisher and his colleagues are pioneering this approach and have already reported success in experiments utilizing UTMD technology and mda-7/IL-24 gene therapy in prostate and colorectal cancer models.

“We are hopeful that this targeted gene therapy could be safely combined with conventional chemotherapies to significantly improve outcomes for patients with breast cancer and potentially a variety of other cancers,” says Fisher. “When paired with promising new delivery techniques such as UTMD, physicians may one day be able to precisely target site-specific cancers and also monitor the effectiveness of these types of therapies in real time.”

Fisher collaborated on this study with Paul Dent, Ph.D., member of the Developmental Therapeutics program at VCU Massey, professor in the Department of Neurosurgery at VCU School of Medicine and member of VIMM; Xiang-Yang Wang, Ph.D., member of the Cancer Molecular Genetics program at VCU Massey, associate professor in the Department of Human and Molecular Genetics and associate scientific director of immunology and infectious diseases of VIMM; Devanand Sarkar, M.B.B.S., Ph.D., Harrison Scholar and member of the Cancer Molecular Genetics program at VCU Massey, associate professor in the Department of Human and Molecular Genetics at VCU School of Medicine, and associate scientific director of cancer therapeutics at VIMM; Belal Azab, Ph.D., and Michelle E. Menezes, Ph.D., both postdoctoral scientists from the Department of Human and Molecular Genetics at VCU School of Medicine; and Sujit K. Bhutia, Ph.D., Department of Human and Molecular Genetics at VCU School of Medicine, now an assistant professor in the Department of Life Science, National Institute of Technology, Rourkela, India.

This study was supported by National Cancer Institute grants R01 CA097318 and P01 CA104177.

The full manuscript of this study is available at: http://onlinelibrary.wiley.com/doi/10.1002/ijc.28289/abstract;jsessionid=EAF95F3253E44B492D50B8E862E1F55E.d03t03

Lung cancer: smoking and lesser-known risk factors

More men die in the United States from lung cancer than any other kind of cancer, and it is estimated that adult male smokers lose an average of 13.2 years of their life. Although it is widely known that smoking is the leading cause of lung cancer, it can also lead to other cancers, such as pancreatic, head and neck, esophageal, kidney, stomach, colon, acute myelogenous leukemia and ovarian cancers. Smoking cessation can significantly reduce your risk. Learn more about quitting.

Although smoking causes more than 80 percent of all lung cancers, people who do not smoke can also get lung cancer. Additional risk factors include: use of other types of tobacco, such as pipes or cigars; secondhand smoke; exposure to harmful chemicals, such as radon gas or asbestos; and personal history, such as having had radiation therapy or a family history of lung cancer.
Learn more about lung cancer.

Prostate cancer: new research sparks changes in screening guidelines

Prostate cancer is the second leading cause of cancer death among men. However, since the adoption of the prostate-specific antigen (PSA) test, which measures the level of PSA in a man’s blood, there has been a 39 percent reduction in mortality rates.

Despite reducing cancer deaths, the test has recently been under scrutiny due to its potential adverse side effects, such as overdiagnosis and overtreament.

Last year, the U.S. Preventive Services Taskforce recommended that men not get a PSA test anymore. Most recently, the American Urological Association (AUA) changed its guidelines to recommend that men under the age of 55, who at average risk of prostate cancer should not get tested. They also recommend against screening men over the age of 70 who have a life expectancy less than 10-15 years.

With conflicting information and guidelines, it is important to talk to your doctor about your individual risk for prostate cancer and educate yourself about the pros and cons of testing.

To learn more about prostate cancer and PSA testing, join us as Jinxing Yu, M.D. from the Virginia Commonwealth University Department of Radiology gives a free health seminar on “Advanced Prostate Imaging: Knowing Not Guessing” at Lewis Ginter Botanical Gardens on June 19, 2013 at 5:30 p.m. Learn more about this event.

Colon cancer: researchers find that simpler colonoscopies are safer

Although colorectal cancer is the third most common cancer in both men and women, the mortality rates have been declining thanks to preventative screening and increased awareness of the disease.

The most common form of colorectal screening is a colonoscopy, which uses a flexible fiberoptic tube to check for cancer or polyps in the colon or rectum. There are many ways that colonoscopies are performed, and as the complexity increases, there is a higher risk of adverse events such as GI bleeding or colonic perforation. New findings from VCU Massey researchers have found that simpler colonoscopies are safer.

The American Cancer Society recommends that those who have no identified risk factors should begin regular screening at age 50. Those who have a family history or other risk factors for colorectal polyps or cancer should talk with their doctor about starting screening at a younger age and/or getting screened more frequently.

Risk factors specific to men include:

• Age: over 90 percent of colorectal cancer cases are in men over age 50
• Family history: if people in your immediate family or near relations had colorectal cancer at a young age, you should be screened earlier than at age 50
• Previous colorectal cancer: if you’ve had cancer removed already, you’re at higher risk of developing a new one
• Inflammatory bowel disease: if you have had a condition such as Crohn’s disease or ulcerative colitis for several years
• Lifestyle factors: drinking more than two alcoholic drinks per day, obesity, smoking, diabetes and a high-fat diet

To learn more about colorectal cancer, join us as gastrointestinal cancers expert Steven R. Grossman, M.D., Ph.D., division chair in Hematology, Oncology and Palliative Care at VCU Massey, discusses advanced treatment, risk factors and the latest screening guidelines during a free health seminar at the Lewis Ginter Botanical Gardens on July 11, 2013 at 5:30 p.m. Learn more about this event.

Skin Cancer: more prevalent in men due to neglect and overexposure

Skin cancer is the most common type of cancer in both men and women, accounting for nearly half of all cancers in the United States. But, men over the age of 50 are more than twice as likely to develop and die from skin cancer as women.

According to the Skin Cancer Foundation, men aren’t naturally more vulnerable to skin cancer than women, but the problem roots from more sun exposure and fewer visits to the doctor. The Foundation states that, “the combination of exposure and neglect is especially dangerous when it comes to melanoma, the deadliest form of skin cancer.” Additionally, middle-aged and older men are the least likely to perform skin self-exams or visit the dermatologist. They are also less likely to use sunscreen properly or at all.

The keys to overcoming skin cancer are prevention, early detection and prompt treatment. Learn more about preventative measures such sunscreen and how to perform a self-skin exam on the Massey News blog.

Human papillomavirus (HPV)

According to the U.S. Centers for Disease Control and Prevention (CDC), approximately 79 million Americans are currently infected with the human papillomavirus (HPV) and about 14 million people will become newly infected each year. The CDC goes on to say that “HPV is so common, nearly all sexually- active men and women will get at least one type of HPV at some point in their lives.” As a growing epidemic, HPV is not only the most common sexually transmitted infection, but also a rising cancer causer.

What is HPV?
There are more than 40 types of HPV that can infect both males and females. HPV is passed through genital contact and vaginal, anal or oral sex. Most people who become infected with HPV show no signs or symptoms.

Screening and prevention
Currently, there are no routine screening tests recommended for HPV-related health effects, such as genital warts or cancers of the vulva, vagina, anus, penis and oropharnyx other than cervical cancer. A Pap test and HPV test can check for the virus that causes cell changes in the cervix that can become cancer.

For prevention, the CDC recommends HPV vaccination (Cervarix or Gardasil) for 11-12 year old boys and girls. HPV vaccines are considered to be safe and effective, and can protect males and females against some of the most common types of the virus.

• Females: Both vaccines are available to protect females against the strains of HPV that cause most cervical cancers. Gardasil also protects against most genital warts and anal, vaginal and vulvar cancers. Females aged 13-26 may also receive the vaccine if they did not when they were younger.
• Males: Gardasil is also available to protect males against the strain of HPV that causes most genital warts and anal cancers. Males aged 22-26 may also get the vaccine.

Things to keep in mind when considering vaccinating yourself or your child: the vaccination does not protect against all types of HPV, so you will still need regular cervical cancer screenings; the vaccine requires three shots taken within a six-month period; some people may not receive the full benefit of the vaccine because they may have already been exposed to HPV; and as with any vaccine, the HPV vaccine has possible risks and side effects. Consult with your doctor about screening and vaccination to help determine the best steps for you to reduce your risk of HPV.

For those who are sexually active, condoms may lower the risk of HPV. The CDC advocates that, “to be most effective, condoms should be used with every sexual act, from start to finish.” But the CDC also advises: “HPV can infect areas that are not covered by a condom, so condoms may not fully protect against HPV.”

Another way to lower your risk of HPV is by being monogamous and limiting your number of sexual partners. Even still, since the disease is so common, people with only one lifetime partner can also get HPV.

HPV and cancer
HPV infections can cause serious health conditions, including genital warts and cervical, vaginal, vulvar, penile, anal and oropharyngeal (head and neck) cancers. The most common HPV-associated cancer is cervical cancer, and almost all cervical cancers are caused by HPV, which is why cervical cancer screening and vaccinations are important. You can also help lower your risk of oropharyngeal cancers by avoiding tobacco and limiting alcohol intake, both of which account for 75 percent of head and neck cancers, especially cancers of the mouth and throat.

Learn more at http://www.cdc.gov/std/hpv/stdfact-hpv.htm.

Results of the 27-patient prospective trial were recently published in the journal Radiation Oncology. The device known as the BioProtect Balloon Implant was tested on patients with localized prostate cancer. It is designed to reduce radiation exposure to the rectum by expanding to increase the space between the rectum and the prostate. It remains in place throughout the treatment process and is designed to biodegrade completely within six months.

“We found that the addition of BioProtect reduced the radiation dose delivered to the rectum by an average of about 30 percent,” says local primary investigator Mitchell Anscher, M.D., Florence and Hyman Meyers Chair of Radiation Oncology at VCU Massey Cancer Center. “Most notable was the device’s ability to reduce exposure at higher radiation levels, which indicates that the cancer could be safely treated with more aggressive protocols.”

The researchers observed a greater reduction in radiation exposure to the rectum at increasing radiation dose levels. At 50 percent of prescribed dose, there was little difference in rectal tissue exposure. However, there was a 55.3 percent reduction at 70 percent of the prescribed dosage, a 64 percent reduction at 80 percent of the prescribed dosage, a 72 percent reduction at 90 percent of the prescribed dosage and an 82.3 percent reduction at 100 percent of the prescribed dosage.

As anticipated, all implanted balloons started to degrade three months after implantation. The researchers concluded that the device could be especially useful in hypofractionated radiation therapy. Hypofractionated radiation therapy uses larger doses of radiation applied over a shorter number of treatments instead of delivering a small percentage of the total dose during daily treatments spread over a longer period of time.

“Massey has many patients that travel from rural areas for care. If this device allows us to deliver the prescribed radiation dose over a shorter period of time, we can reduce the overall burden on the patient and they can spend less time away from work and their family,” says Anscher. “We hope to initiate a Phase II clinical trial in a larger cohort of patients in order to determine the effectiveness of the device in reducing rectal injury in comparison to standard treatment protocols.”

Anscher collaborated with the study’s lead investigator Gyorgy Kovacs, M.D., Ph.D., from the University of Lubeck, Germany; Dieter Jocham, M.D., and Gunther Bohlen, M.D., also from the University of Lubeck; Eliahu Gez, M.D., Rami Ben Yosef, M.D., Benjamin W. Corn, M.D., and Fabrizio Dal Moro, M.D., all from the Department of Radiation Oncology at Tel Aviv Sourasky Medical Center, Israel; Giovanni Scarzello, M.D., from the Department of Radiotherapy at the University of Padova, Italy; and Isaac Koziol, M.D., Mathew Bassignani, M.D., and Taryn Torre, M.D., all from Virginia Urology; and Shmuel Cytron, M.D., from Barzilai Medical Center, Israel.

The full manuscript of the study is available online at: http://www.sciencedirect.com/science/article/pii/S0167814013000236

Charles Edward Geyer, Jr., M.D., F.A.C.P., has been named associate director for clinical research at Virginia Commonwealth University Massey Cancer Center and a professor in the Division of Hematology, Oncology and Palliative Care, Department of Internal Medicine, at the VCU School of Medicine, effective June 1, 2013.

Geyer comes to VCU from The University of Texas Southwestern Medical Center in Dallas, where he was an associate professor in the Division of Hematology/Oncology. He was also previously president and chief medical officer of the Statewide Clinical Trials Network of Texas (CTNet), a network of academic and community-based cancer centers across Texas collaborating on cancer clinical research.

A board certified medical oncologist and clinical researcher, Geyer is internationally recognized for his expertise in the study and treatment of breast cancer. From 2004 to 2011, he served as the director of medical affairs at the National Surgical Adjuvant Breast and Bowel Project (NSABP), where he was responsible for the development and oversight of the national cooperative group’s clinical studies for breast and colorectal cancers. He was also the founding co-chairman of the NCI (National Cancer Institute) Breast Cancer Steering Committee, which coordinates the nation’s process for identifying and promoting the “best science” in breast cancer clinical research by addressing the design and prioritization of phase 3 and large phase 2 trials for breast cancer.

As the associate director for clinical research at Massey, Geyer will serve on the cancer center’s Executive Committee and will oversee the development of and play a key role in defining the strategic vision of oncology clinical trials at Massey. He will collaborate with laboratory and clinical investigators of the cancer center’s various scientific programs as well as with its oncology clinicians to fashion a clinical trials menu that reflects both the strengths of Massey’s science and the cancer burden of its patients. He will also work closely with the associate director of translational research, Steven Grant, M.D., to create a seamless pathway for moving promising new scientific concepts into clinical trials.

“We are very pleased to welcome Dr. Geyer to Massey to direct our clinical research enterprise,” said Gordon D. Ginder, M.D., director of VCU Massey Cancer Center. “He brings substantial expertise and experience to a leadership position critical to Massey’s long-term growth and continued success as Virginia’s largest provider of cancer clinical trials.”

“Dr. Geyer’s prominence as a breast cancer specialist further strengthens our division’s excellence in patient care, research and education,” said Steven Grossman, M.D., Ph.D., chair of the Division of Hematology, Oncology and Palliative Care. “His addition will not only benefit the cancer center and university, but also the cancer community across Virginia.”

Geyer received his undergraduate and medical degrees from Texas Tech. He completed a residency in internal medicine and fellowship in medical oncology at Baylor College of Medicine Affiliated Hospitals, and he served as chief medical resident at Houston Veterans Administration Medical Center. He and his wife, Joni, have four children.