MiRNAs are small (19-25 nucleotides long), non-coding RNAs that down-regulate gene expression. Their expression has been linked over the past 5 years or so to hematopoiesis and to cancer in both humans and mice.

The first report associating miRNAs and cancer involved chronic lymphocytic leukemia. Because of the specific mechanisms causing AML, and because patients with AML often have a relatively poor prognosis, creating a need for novel therapies, the researchers attempted to determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in AML.

Dr. Ramiro Garzon of Ohio State University in Columbus and colleagues obtained bone marrow and blood samples from 182 untreated patients newly diagnosed with AML. Using a microarray system, the researchers analyzed the miRNA expression in 122 of these AML samples; the other 60 pretreatment samples were used to validate the miRNA signatures with quantitative real-time PCR. (A second cohort of 54 patients with relapsed or refractory AML was also evaluated.)

The researchers found a “distinct spectrum” of miRNA expression in the AML patients versus normal CD34+ progenitor cells, identifying 26 down-regulated miRNAs and none that were up-regulated. PCR testing of seven miRNAs validated all but one.

“Similar miRNAs signatures to those of the untreated patients were obtained” from the relapsed/refractory AML patients, the researchers wrote, “thereby supporting the hypothesis that miRNA expression is largely driven by cytogenetics.”

“We currently start patients (chewing gum) on the day after surgery, chewing one stick three times per day,” Dr. Raj S. Pruthi said. “The outcome, a return of bowel function, was faster in the gum-chewing group, perhaps due to reflexes in our body, such as orogastric and orocolic reflexes, that may stimulate gastrointestinal activity with chewing.”

Dr. Pruthi and colleagues at The University of North Carolina at Chapel Hill studied two groups of patients undergoing radical cystectomy with urinary diversion for bladder cancer. The first group of 51 patients underwent surgery between July 2004 and August 2005 and served as controls. The second group, also 51 patients, underwent surgery between September 2005 and July 2006. This group began chewing gum the day after surgery.

The researchers compared time to flatus, time to bowel movement, hospital length of stay and the complication rate between the two groups.

Time to flatus was 2.4 days for the gum-chewing patients and 2.9 days for controls. Time to bowel movement was 3.2 days and 3.9 days for study patients and controls, respectively. Hospital length of stay was not significantly different between the two groups.

“The gum chewing had no side effects, as would be expected,” Dr. Pruthi noted. “In fact, most patients enjoyed it to stimulate their salivation and keep their mouth wet.”

The study is published in the December issue of Urology.

“Gum chewing is a simple, safe, inexpensive, readily available, innocuous treatment with some potential real benefits with regard to bowel and overall recovery,” Dr. Pruthi said. “Thus, there is seemingly little or no downside to such an intervention and something that can be readily given to most patients.”

Nexavar (Bayer AG and Onyx Pharmaceuticals) dramatically reduced the percentage of circulating leukemia cells in 16 subjects with a mutation in the FLT3 gene, which occurs in about one third of AML patients.

“AML patients with this mutation have a particularly poor prognosis, so this highly targeted drug appears to be a significant step forward in leukemia therapy,” said Dr. Michael Andreeff of the M.D. Anderson Cancer Center at the University of Texas.

Circulating cancer cells in study patients dropped to 7.5%, from 81%. In two patients, leukemia cells circulating in the blood dropped to zero, the researchers reported in the Journal of the National Cancer Institute.

The study patients had failed all other treatments.

Dr. Andreeff said in a statement that Nexavar would need to be combined with other treatments. So far, there have been no major side effects.

Andreeff said the drug has little effect on AML patients who do not have the genetic defect.

A study last week in the journal Lancet Oncology, however, found the drug significantly raises the risk of hypertension, and researchers said patients should be monitored for this risk.

Nexavar was recently approved to treat liver cancer in the United States and Europe. It is currently being tested for use against several other types of cancer, including non-small cell lung cancer and breast cancer.

Because it has been attenuated through passage in chicken embryo fibroblasts, MVA replicates poorly in nonavian cells. Its safety profile indicates that it may be a useful alternative to Dryvax for immunocompromised individuals, individuals with atopic dermatitis, children, and pregnant women, for whom Dryvax is contraindicated. It is also being considered for immunization prior to Dryvax administration to reduce Dryvax reactogenicity.

However, there have been concerns that the genetic mutations and deletions in MVA may have affected its immunogenicity, lead author Dr. D. Huw Davies at the University of California, Irvine, and associates note. They theorize that “since the structural genes appear to be intact in MVA…critical targets for antibody neutralization have been retained.”

To compare the humoral responses elicited by MVA and Dryvax vaccines, the researchers applied blood serum from vaccinated humans and macaques to microarray chips containing vaccinia virus proteins.

“The MVA and Dryvax antibody profiles were broadly similar, with antibodies against membrane and core proteins being the best conserved,” the authors report.

Moreover, human and macaque immune profiles were very similar, verifying the macaque as “a close model for human antibody response.”

Dr. Davies’ team also tested a regimen involving a first vaccination with MVA followed by a Dryvax “boost,” to see if preexisting immunity to MVA would block Dryvax infectivity.

“We found that immunization of macaques with MVA followed by Dryvax engendered a profile indistinguishable from that achieved with Dryvax alone,” the team reports, indicating that “the MVA prime-boost regimen does not diminish the immunogenicity engendered by Dryvax.”

Previous studies demonstrated that preservation of the neurovascular bundle can improve post-operative potency rates, but whether nerve-sparing surgery improves incontinence was unclear, senior author Dr. Craig D. Zippe, from the Cleveland Clinic Foundation, and colleagues note in the December issue of Urology.

To investigate, the researchers assessed incontinence rates in 152 patients who underwent radical prostatectomy with unilateral or bilateral nerve sparing or with no nerve sparing.

During an average follow-up period of 7.8 years, 27 patients (17.7%) were incontinent. Eighteen of 61 patients treated with non-nerve-sparing surgery were incontinent compared with just 6 of 66 treated with bilateral nerve-sparing surgery (p < 0.05). By contrast, unilateral nerve sparing offered no benefit over non-nerve sparing.

In addition to the type of surgery, patient age also affected incontinence rates; subjects older than 65 years were significantly more likely to become incontinent than were younger patients.

“This study suggests that all patients, irrespective of potency status and age, would benefit from nerve-sparing procedures when this is clinically feasible,” the authors conclude.

HIF-1a has the potential to normalize intracellular oxygen levels by increasing the synthesis of multiple proangiogenic cytokines and genes that facilitate survival of ischemic tissue, the authors explain.

Dr. Sanjay Rajagopalan from Ohio State University, Columbus, Ohio and colleagues investigated the safety of a modified, constitutively active form of HIF-1a (Ad2/HIF-1a/VP16) in patients with advanced atherosclerosis and tissue ischemia.

All but one of the patients treated with HIF-1a experienced adverse events, the authors report, but most events were mild or moderate in severity and not serious.

The time to treatment failure or amputation did not differ significantly between the HIF-1a and placebo groups, the results indicate, but a smaller proportion of HIF-1a patients (7 out of 34) than placebo patients (3 out of 7) met treatment failure criteria.

A similar proportion of treated and placebo patients experienced dependent edema of the lower extremities and injection site reactions, the researchers note, but there was no evidence for promotion of tumor growth, choroidal neovascularization, or new or active proliferative retinopathy.

Fourteen of 32 HIF-1a patients alive at 1 year had complete rest pain resolution, the report indicates, and 5 of 18 had complete ulcer healing.

Clinical improvement did not correlate with improvements in ankle-brachial index or with MR angiography results, the investigators say.

“These data provide encouraging initial evidence of a potentially important therapeutic approach in the treatment of vascular disease without evidence of serious toxicity,” the authors conclude. “Additional, appropriately powered clinical trials are needed to evaluate the safety and efficacy of modified constitutively active forms of HIF-1a in peripheral arterial disease.”

“Evidence is accumulating that insulin resistance and hyperinsulinemia are involved in the etiology of endometrial cancer,” Dr. Susanna C. Larsson and colleagues from Karolinska Institute, Stockholm, Sweden, write. “Obesity, physical inactivity, and type 2 diabetes mellitus are all associated with insulin resistance, hyperinsulinemia, and endometrial cancer.”

The researchers studied 61,226 participants of the Swedish Mammography Cohort who were cancer-free at enrollment between 1987 and 1990 and completed a food frequency questionnaire.

The subjects were followed-up for a mean 15.6 years through June 2005. During that time, a total of 608 incident cases of endometrial adenocarcinoma were diagnosed. There was no overall association observed between carbohydrate intake, glycemic index or glycemic load and the incidence of endometrial cancer. For the highest versus the lowest quintiles, the rate ratios (RRs) were 1.12 for carbohydrate intake, 1.00 for glycemic index, and 1.15 for glycemic load.

In a subanalysis of women who completed a follow-up questionnaire in 1997 that included information on physical activity, researchers found a positive association between carbohydrate intake and glycemic load and endometrial cancer among overweight women with low physical activity.

“In summary, in this prospective study, we observed no overall association of carbohydrate intake, glycemic index or glycemic load with endometrial cancer risk,” the authors conclude. “However, our findings suggest that a high carbohydrate intake and a high-glycemic load diet may be associated with an increased risk of endometrial cancer among overweight women with low physical activity.”

“The presence of hair in a pigmented lesion should not automatically mean that the lesion under investigation is benign,” Dr. Ashfaq A. Marghoob from Memorial Sloan-Kettering Cancer Center, New York said. “One needs to evaluate the primary morphology of the lesion in question and base one’s decision on that.”

Dr. Marghoob and associates sought to dispel the myth of the “benign hair sign” by reporting 3 cases of melanocytic lesions that showed terminal hairs on clinical and dermoscopic evaluation, but in which the final diagnosis was invasive melanoma.

In all 3 cases, terminal hair shafts could be clearly seen to protrude from the tumor, the authors report. Nevertheless, clinical, dermoscopic, and histopathological examination confirmed the presence of invasive melanoma.

“This may be due to the fact that the melanoma arose on a hair-bearing surface or arose in association with a nevus with hair without causing destruction of the hair follicles,” the investigators say.

“It is very common (70-80%) for congenital melanocytic lesions to have increased hair,” Dr. Marghoob added. “Thus, if hair is present within a pigmented lesion it is most likely to be a congenital melanocytic nevus. However, the presence of hair does not exclude the presence of melanoma.”

Bladder cancer is common in the U.S., representing about 6% of all new cancer cases among men and 2% among women, Anna E. Prizment and colleagues report in the March issue the International Journal of Cancer. “Established risk factors for bladder cancers include age, gender, smoking and chemical carcinogens.”

The researchers examined the association between reproductive factors and bladder cancer in a prospective cohort study of 37,459 women (between the ages of 55 and 69 years) from Iowa. The women were initially free from cancer in 1986. The participants reported reproductive history and were followed through 2003.

During follow-up, a total of 192 women (0.5%) were diagnosed with bladder cancer at an average age of 73 years. An inverse association was observed between age at menopause and incident bladder cancer after adjusting for age and smoking.

Compared with women who reached menopause at age 48 or later, the hazard ratio (HR) of bladder cancer was 1.32 for women who reached menopause between 43 and 47 years, and 1.60 for those younger than 42 years (p for trend = 0.02). These associations were comparable for natural and surgical menopause.

The risk of bladder cancer was also increased among women with a history of bilateral oophorectomy compared to those who did not undergo bilateral oophorectomy (HR = 1.58) and the researchers noted a trend between bladder cancer and fewer lifetime years of ovulation.

No associations were found between bladder cancer and any other reproductive factors including age at menarche, age at first birth, number of births, hormone replacement therapy use, infertility, fibroid tumors, ovarian cysts or endometriosis.

“Earlier it was suggested that the deficiency of endogenous estrogen after menopause could lead to an increased number of urinary tract infections associated with bladder cancer,” Prizment said “This may explain why we observed associations between bladder cancer and only those reproductive factors which were related to menopause.”

However, Prizment added: “It is too early to make any definite conclusions since the biological mechanism of this association is unclear.”

Xeloda was approved for first-line use in combination with platinum-based chemotherapy, Roche said in a statement.

The approval had been expected after Xeloda — which is already approved for other conditions — was recommended for stomach cancer last month by a panel of European experts.

The decision was based on data from two late-stage clinical trials. One trial showed that patients given a combination of Xeloda and cisplatin lived at least as long without cancer progressing as those receiving the current standard therapy of cisplatin plus 5-flurouracil. The second study demonstrated Xeloda was as effective as 5-flurouracil and can replace it.