Transplanted embryonic stem cells are recognized as a potential treatment for patients suffering from the effects of spinal cord injury (SCI). However, in studies using embryonic stem cells transplanted into SCI laboratory animals, a serious drawback has been the development of tumors following transplantation.

Publishing in the current issue of Cell Transplantation (Vol. 18 No.1), a team of Japanese researchers describe their study that demonstrates a way to eliminate the problem of tumor growth by co-transplanting bone marrow stem cells (BMSCs) along with embryonic stem cells.

“Our study results suggest that co-transplanting BMSCs induce undifferentiated embryonic stem cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation in SCI model mice,” said corresponding author Dr. Masahide Yoshikawa of the Nara Medical University. “The known multipotency of BMSCs during differentiation and their known ability to produce neurotrophic factors, such as nerve growth factor, led us to speculate that co-transplantation of ES cells and BMSCs would provide an advantage over transplantation of ES cells alone.”

A control group of mice that only received ES cells developed tumors at the grafted site and their behavioral improvement ceased after three weeks. No tumors developed in the co-transplantation group and behavioral improvement continued over the five-week study.

To date, no effective medical therapy has been available for SCI patients. While ES cells have been thought to represent a potential resource for therapy, the hurdle of tumor formation has impeded efforts. Co-transplantation of BMSCs appears to overcome the tumor hurdle, suggesting to the researchers that their success can provide a path toward human trials.

“The entire mechanism of suppressed tumor development following co-transplantation remains to be elucidated,” says Dr. Yoshikawa. “We considered that the BMSCs played an important role in preventing tumors and speculate that one of the mechanisms by which BMSCs promote the differentiation of ES cells is related to secreted soluble factors, including neurotrophic factors.”

According to Dr. Yoshikawa, the transplanted BMSCs survived in the grafted site for at least five weeks after transplantation and maintained their ability to produce NGF.

“These findings are extremely important and emphasize the need for additional study on how embryonic stem cells may be used to treat human neurological problems in the not too distant future,” commented Section Editor Dr. John Sladek, professor of pediatrics and neuroscience at the University of Colorado School of Medicine.

Source:
Dr. Masahide Yoshikawa

Cell Transplantation Center of Excellence for Aging and Brain Repair

HOUSTON, May 12 — Confounding the common epidemiological wisdom, urban dwellers had a higher risk of four common, late-stage cancer diagnoses than their rural counterparts in a new, population-based analysis.

• Explain to patients that this study showed that the risk of late-stage cancer diagnosis was highest in the largest city and decreased as residents lived in more rural areas.
• Note that the findings were based on an analysis of cancer epidemiology in one state.

Residents of the most urbanized areas had the highest risk of breast, colorectal, lung, and prostate cancer, Sara McLafferty, Ph.D., and Fahui Wang, Ph.D., of the University of Illinois Urbana-Champaign, reported online in Cancer.

Cancer risk decreased with increasingly rural residency, except for a slight upturn in the most isolated communities.

“We observe a reversal of the commonly held view that risks are highest for rural residents,” the authors concluded.

“The concentration of health disadvantage in highly urbanized places emphasizes the need for more extensive urban-based cancer screening and education programs, especially programs targeted to the most vulnerable urban populations and neighborhoods.”

The authors identified several variables that could account for some of the variability. However, some findings had no ready explanations. For example, residents of large towns in rural areas consistently had lower cancer risks.

Data on urban-rural cancer disparities have been mixed. Authorities in the field generally supported the notion that residents of rural areas had a greater risk of late-stage diagnosis because of reduced access to screening services.

The authors continued the assessment in an analysis that focused on the rural-urban gradient of late-stage cancer risk in Illinois for 1998 through 2002. Using data from the State of Illinois Cancer Registry, they limited the analysis to four major types of cancer: breast, colorectal, lung, and prostate.

For the study period, the authors determined that late-stage diagnosis accounted for 36.9% of breast cancers, 62.9% of breast cancers, 79.7% of lung cancers, and 15.6% of prostate cancers.

To analyze late-stage diagnosis by geographic area, the authors used a modified version of the Rural-Urban Commuting Areas (RUCA) classification system developed by the U.S. Office of Rural Health Policy.

The modifications resulted in five classifications: Chicago, Chicago suburbs, other metropolitan areas, large towns (population 10,000 to 50,000), and rural areas (population <10,000).

Analysis of late-stage cancer diagnosis by the five geographic areas revealed a “clear and remarkably consistent rural-urban gradient in late-stage risk,” the authors said. “Risk is highest in Chicago, decreases in the less urbanized zones, and reaches a nadir in other metropolitan areas and large towns.”

The risk increased somewhat among patients living in the areas classified as rural, resulting in a reverse-J gradient along the urban-rural continuum. The gradient held up for all four types of cancer.

The gradients were steepest for breast, colon, and lung cancer, all of which had the lowest odds ratios in large towns and the highest ratios in Chicago. As compared with Chicago, the odds ratio for large towns ranged between 0.71 and 0.79 for those three cancers.

Age and racial/ethnic variation accounted for some of the disparities. However, some of the disparities persisted in multivariate analysis that accounted for the differences.

As an example, the authors noted that “all other factors being equal, patients who live outside the Chicago area are 25% to 35% less likely than their Chicago-area counterparts to present with late-stage lung cancer.”

The authors reported no competing interests.

Primary source: Cancer

Source reference:
McLafferty S, Wang F “Rural reversal? Rural-urban disparities in late-stage cancer risk in Illinois” Cancer 2009; DOI: 10.1002/cncr.24306.

Eligible patients with newly diagnosed glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer, are enrolling in the ACT III clinical trial of a vaccine called CDX-110, which may prevent recurrence and extend survival. Physician-scientists at NewYork-Presbyterian Hospital, together with Weill Cornell Medical College and Columbia University Medical Center, are helping to lead the Phase II multicenter trial of the vaccine, which is thought to work by “training” the immune system to target and kill cancer cells.

“Even after surgery, radiation and chemotherapy, this deadly brain cancer has a high likelihood of recurrence. This experimental vaccine is designed to harness the body’s immune system to keep the cancer at bay,” says Dr. Theodore Schwartz, site principal investigator and neurosurgeon at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, and associate professor of neurological surgery at Weill Cornell Medical College.

“Results from earlier trials are promising, and suggest that the vaccine may be able to improve both time to disease progression and length of survival,” says Dr. Rose Lai, site principal investigator and neuro-oncologist at NewYork-Presbyterian Hospital/Columbia University Medical Center, and assistant professor of neurology in the Division of Neuro-Oncology at Columbia University College of Physicians and Surgeons.

Glioblastoma multiforme commonly causes memory, personality and neurological deficits, but may also produce seizures, nausea and vomiting, headache, and weakness on one side of the body (hemiparesis). The location of the tumor plays a role in what types of symptoms a patient may suffer. Until it is large enough, the tumor may not cause any symptoms. About 10,000 people are diagnosed with the disease each year.

An initial single-arm Phase II trial (ACT II) has reported promising preliminary data in 23 patients who received CDX-110. Median time to disease progression was 16.6 months and estimated median overall survival was 33.1 months. This compared favorably with data for a historical control group in which median time to progression was 6.4 months and median overall survival was 15.2 months.

The ACT III study will look at the effectiveness of the vaccine plus temozolomide in patients who are newly diagnosed with glioblastoma multiforme. Patients will receive injections into the skin every two weeks for three doses shortly after the completion of cranial radiation, followed by monthly injections for as long as the tumor has not returned. Temozolomide chemotherapy will be given one week after each monthly injection of the vaccine and continued for up to 12 cycles.

Qualifying patients must be 18 or older, have newly diagnosed and surgically resected glioblastoma multiforme. Interested patients should be screened for the study immediately following surgery. Qualifying patients must have cancer that expresses the protein epidermal growth factor receptor variant III (EGFRvIII). About 20 percent to 25 percent of patients with GBM express the EGFRvIII mutation. The vaccine is expected to work by activating the immune system against the EGFRvIII protein, shutting down the engine room of cancer growth in these patients. Patients must also have had a near total resection of their tumors and must be able to undergo combined radiation with temozolomide in order to qualify.

“If this approach is validated, vaccine therapy could be added on to the existing regimen of combined chemo-radiation,” says Dr. Schwartz.

The study is sponsored by Celldex Therapeutics Inc. of Phillipsburg, NJ.

Cancer Vaccines

Cancer vaccines are intended either to treat existing cancers (therapeutic vaccines) or to prevent the development of cancer (prophylactic vaccines). Therapeutic vaccines, which are administered to cancer patients, are designed to treat cancer by stimulating the immune system to recognize and attack human cancer cells without harming normal cells. Prophylactic vaccines are given to healthy individuals to stimulate the immune system to attack cancer-causing viruses and prevent viral infection. Currently, two vaccines have been licensed by the U.S. Food and Drug Administration to prevent virus infections that can lead to cancer: the hepatitis B vaccine, which prevents infection with the hepatitis B virus, an infectious agent associated with liver cancer; and Gardasil®, which prevents infection with the two types of human papillomavirus that together cause 70 percent of cervical cancer cases worldwide.

Source

NewYork-Presbyterian Hospital

View drug information on Gardasil.