Green Tea Compound in Chemoprevention of Cervical Cancer

Human papillomavirus (HPV) infection is closely associated with the development of more than 95% of cervical cancer. Clinical trials using several chemopreventive agents are underway, but results are inconclusive. Most agents used in trials inhibited the growth of cancer cells in vitro, and about half of patients had some degree of clinical responses; however, the therapeutic effect was confounded by high rates of spontaneous regression and relapse. The selection of nontoxic agents especially food, beverage, and natural products that suppress oncogenic HPV, inhibit malignant transformation, and can additionally be used long term may be important for cervical cancer prevention.

Methods: We evaluated green tea compound (epigallocatechin gallate and polyphenols E) effects on immortalized cervical epithelial and cervical cancer cells. HPV-immortalized cervical epithelial cells, TCL1, and HPV-positive cervical cancer cells, Me180 and HeLa, were used in the study. The effects of green tea compounds on cell growth, apoptosis, cell cycle, and gene expression were examined and characterized.

Results: Both epigallocatechin gallate and polyphenols E inhibited immortalized cervical epithelial and cancer cell growth. Apoptosis induction and cell cycle changes were observed in a dose-dependent manner. Western blot analysis of apoptosis-related proteins, p53 and p21, showed dose-dependent increase, whereas p27 was not affected. HPV-E7 protein expression was decreased by green tea compounds.

Conclusions: This study provides information on the potential mechanisms of action of green tea compounds in suppression of HPV-related cervical cells, and it will enable us to assess the feasibility of using these agents.

source: American journal of clinical oncology

Development of COX Inhibitors in Cancer Prevention and Therapy

On the strength of in vitro, in vivo, observational, and clinical data, nonsteroidal antiinflammatory drugs (NSAIDs)-also referred to as COX inhibitors-have emerged as lead compounds for cancer prevention, and possible adjuncts to cancer therapy. Thus far, the routine use of NSAIDs for these indications is limited, largely owing to toxicity concerns, the paucity of efficacy data for any specific target organ, and uncertainties with regard to the most appropriate regimen (i.e., the best agent, formulation, dose, route of administration, and duration). Strategies to address these concerns primarily aim to improve the therapeutic index (i.e., benefit:risk ratio) of COX inhibitors by 1) minimizing systemic exposures whenever feasible, 2) achieving greater mechanistic specificity, 3) coadministering agents that provide prophylaxis against common toxicities, and 4) coadministering other effective anticancer agents. Clinical trials testing most of these strategies have been completed or are under way. The National Cancer Institute has a substantial research portfolio dedicated to the identification, testing, and development of NSAIDs as preventive and therapeutic anticancer agents. Discovering how to apply NSAIDs in persons with-or at risk for-cancer, although challenging, has the potential for considerable clinical and public health benefits.

Over the last 30 years, we have come to understand that carcinogenesis advances through cumulative structural and functional genomic aberrations that are sequentially expressed within each, and ultimately across all, higher levels of biologic organization (e.g., organelles, cells, tissues, organ). 1 Crucial aberrations may result in a pathologic imbalance between cellular proliferation and apoptosis, thereby fostering a progressively deviant cell population. Fortunately, organisms are endowed with multiple mechanisms-repair, replacement/recruitment, replication, and redundancy-that can preserve structural and functional integrity. Nevertheless, in some instances these mechanisms are overwhelmed and unrepaired damage goes unchecked, potentially leading to the development of cancer. 2

Understanding the molecular genesis of cancer is integral to advances in cancer prevention and therapy. 3 Technologic innovations in endoscopic and noninvasive imaging, mutation analysis, gene expression, and protein analysis are enhancing our abilities to characterize the cellular and molecular genesis of neoplasia. Data arising from these inquiries are being iteratively transformed into information that can improve cancer risk assessments (i.e., molecular risk profiling), bolster the accuracy and reliability of outcome determinations (i.e., molecular monitoring), and improve anticancer agent identification and development (i.e., molecular targeting).

source: American journal of clinical oncology

Carnosol: A promising anti-cancer and anti-inflammatory agent

The Mediterranean diet and more specifically certain meats, fruits, vegetables, and olive oil found in certain parts of the Mediterranean region have been associated with a decreased cardiovascular and diabetes risk. More recently, several population based studies have observed with these lifestyle choices have reported an overall reduced risk for several cancers. One study in particular observed an inverse relationship between consumption of Mediterranean herbs such as rosemary, sage, parsley, and oregano with lung cancer. In light of these findings there is a need to explore and identify the anti-cancer properties of these medicinal herbs and to identify the phytochemicals therein. One agent in particular, carnosol, has been evaluated for anti-cancer property in prostate, breast, skin, leukemia, and colon cancer with promising results. These studies have provided evidence that carnosol targets multiple deregulated pathways associated with inflammation and cancer that include nuclear factor kappa B (NFκB), apoptotic related proteins, phosphatidylinositol-3-kinase (PI3 K)/Akt, androgen and estrogen receptors, as well as molecular targets. In addition, carnosol appears to be well tolerated in that it has a selective toxicity towards cancer cells versus non-tumorigenic cells and is well tolerated when administered to animals. This mini-review reports on the pre-clinical studies that have been performed to date with carnosol describing mechanistic, efficacy, and safety/tolerability studies as a cancer chemoprevention and anti-cancer agent.

source: cancer latter

Muscular dystrophy findings fuel French stem cell debate

Work shows the value of human embryonic stem cells for disease research.

stem cells
Researchers hope their discovery will show French politicians the need to allow research on human embryonic stem cells

There is no cure for the group of hereditary muscle-wasting diseases known as muscular dystrophy. That is particularly alarming because one of its commonest forms — type 1 myotonic dystrophy — becomes more serious as it passes down the generations, manifesting earlier and acquiring pernicious extra symptoms, such as delays to mental development.

A group of French scientists have now unravelled molecular pathways that may be responsible for some symptoms of type 1 myotonic dystrophy. They used a controversial source of material: disease-specific human embryonic stem (hES) cell lines. They hope that their results, published online today in Cell Stem Cell1, will influence a French political debate that threatens to restrict such work. The French Senate will vote on the issue on 5 April, in the first reading of new legislation to update the country’s bioethics law.

Type 1 myotonic dystrophy results from a defect in just one gene — dystrophia myotonica-protein kinase (DMPK) — but that damage affects the expression of other healthy genes. The team of researchers, led by Cécile Martinat, a geneticist at the Institute for Stem Cell Therapy in Evry, identified two such genes that are suppressed in the disease. They showed that the suppression prevented neurons from efficiently building connections with muscle cells.

Unlike in most genetic diseases, the damaged DMPK gene is not mutated. Instead, its code is interrupted by a long and unstable string of ‘triplet repeats’, in which three of the four nucleotides that make up DNA repeat themselves more than fifty times. The string of repeats tends to get longer with each generation.

“This is an excellent example of the value of using hES cells to study a genetic disease and learn something about its biology,” says Nissim Benvenisty, a geneticist at the Hebrew University in Jerusalem. Benvenisty has also done research on a disease-specific hES cell line, to learn how the damaged gene that causes fragile-X syndrome, the most common inherited cause of developmental delay, initiates the disease2.

Reused embryos

The cell lines used by the French scientists were derived from two embryos carrying the damaged DMPK gene. These embryos had been identified by pre-implantation genetic diagnosis (PGD), a procedure undertaken during in vitro fertilization by couples at high risk of passing genetic disease to their children. A single cell is removed from an embryo before implantation, and its genes are analysed; only healthy embryos are then implanted into the mother. In countries that allow such procedures, discarded embryos carrying disease genes may be grown into cell lines that model the disease.

Martinet’s team developed the hES cells into a class of neuron that would normally connect muscles with nerves. The group looked at gene expression across the whole genome in these cells, comparing it with that in healthy cells, and found 15 genes with altered expression. Two of the those genes belonged to the SLITRK family, which is known to affect how neurons sprout.

The scientists showed that the downregulation of these two genes caused the neural cells to sprout ‘neurite’ projections in abnormally large amounts — but seemingly to little avail. When they incubated the neural cells with muscle cells, the neurites were not able to form their customary neuromuscular contacts as well as they did in control cells.

When the researchers differentiated the hES cells into classes of neural cells that do not supply muscles with nerves, they didn’t find any neurite defects.

Best option

Scientists hope that it will one day be possible to replace hES cells in most experiments and future therapies with reprogrammed adult cells that can differentiate into any cell type, called induced pluripotent stem (iPS) cells.

“But just getting iPS cells with a mutant DMPK gene may not fully mimic the complicated triplet-repeat damage that occurs in type 1 myotonic dystrophy, because of the complex genomic and epigenetic changes associated with reprogramming,” says Marc Peschanski, director of the Institute for Stem Cell Therapy and an author of the latest paper. “Also, iPS cells may not in any case help us understand the critical events in very early development that lead to the myotonic dystrophy syndrome,” he adds.

Indeed, Benvenisty’s team found that, unlike his disease-specific hES cells, iPS cells with the fragile-X mutant gene knocked out did not reproduce the early developmental events leading to fragile-X syndrome3 — which is also caused by a triplet-repeat defect.

Peschanski runs a large iPS-cell research programme in addition to his hES-cell work. “We make iPS cells to model particular diseases when we don’t have access to the relevant hES cells — which remain our gold standard,” he says.

Politicians who oppose hES-cell research often — wrongly — insist that iPS cells can always substitute for hES cells, says Peschanski. He is frustrated that the lower house of the French parliament invoked this argument when proposing a ban on hES-cell research in France. Peschanski has since been working with other French scientists to persuade the Senate to overturn the proposal next week.

source: Nature

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.

source: nature

An Inactivated Yellow Fever Vaccine

Results from a phase I trial support further evaluation of an inactivated, cell-culture–derived vaccine.

The currently used yellow fever vaccine — a live attenuated preparation based on strain 17D — was developed in 1936. Although highly effective, this vaccine can cause serious viscerotropic and neurotropic reactions as well as anaphylaxis. A purified whole-virus, inactivated, cell-culture–derived vaccine (XRX-001) produced using the 17D strain has proven efficacious in animal challenge studies. Now, researchers in the U.S. have conducted a double-blind, dose-escalation, phase I study of this preparation. The study was sponsored by the vaccine developer.

Participants were 60 healthy adults who had never been vaccinated against yellow fever, Japanese encephalitis, or tick-borne encephalitis and had no history of overseas military service or travel in the tropics. They were randomized to receive two intramuscular injections, 21 days apart, of low-dose XRX-001 (0.48-µg formulation), high-dose XRX-001 (4.8-µg formulation), or placebo (0.9% saline). Levels of neutralizing antibodies were measured at baseline and on days 21 (before the second injection), 31, and 42; adverse events were assessed through day 42.

No serious adverse events were recorded, but one high-dose vaccine recipient developed mild urticaria on day 24. Injection-site symptoms were more common among vaccine recipients (at either dose) than among placebo recipients.

Regardless of vaccine dose, two injections were needed to achieve effective immunization. An antibody response was seen 10 days after the second injection in 100% and 88% of the high- and low-dose recipients, respectively. Antibody levels were significantly higher in high-dose than in low-dose recipients (geometric mean titer on day 31, 146 vs. 39; P<0.001).

Comment: It has been 75 years since the development of the live attenuated 17D vaccine. Much more study of the XRX-001 vaccine is needed to determine its role, if any, in yellow fever prevention.

Source:Journal Watch Infectious Diseases


Experience with TachoSil in obstetric and gynecologic surgery



To evaluate the feasibility and effectiveness of using TachoSil during obstetric and gynecologic surgery.


The retrospective cohort study, conducted at a French university hospital, included women who experienced perioperative bleeding requiring the use of TachoSil during 2007–2009. The following information was collected: patient age, indication for the use of TachoSil, need for a blood transfusion, type of surgery performed, postoperative course, and traceability of TachoSil.



TachoSil was used in 84 women. The main indications for the surgical interventions requiring TachoSil were ovarian malignancy (n = 18), fibroma (n = 17), breast cancer (n = 11), and endometrial cancer (n = 10). In 16 women, TachoSil was applied to the uterine serosa, particularly after cesarean delivery or polymyomectomy; in 7 women, it was applied to the major vascular axis. Red cell packs were infused in 24 women during surgery (average 3 packs per woman). Three women required repeat surgery. The use of TachoSil was not recorded in the operative reports of 43 (51%) women.



The present findings confirm that the use of TachoSil in gynecologic and obstetric surgeries is effective and well tolerated. Measures to improve the traceability of TachoSil use are recommended.

source: science direct

Fears and Facts About Antidepressants

Fears and Facts About Antidepressants

Along with counseling, antidepressants are a common part of treatment for depression. And they are usually effective. Six out of 10 people treated with antidepressants feel better with the first one they try. If the first antidepressant medication doesn’t help, the second or third often will. Most people eventually find one that works for them. Yet many people who could benefit from an antidepressant never try one, often because of fears and misconceptions about them, experts say.

Here are eight common fears about antidepressants, as well as facts that can help you decide if an antidepressant might be right for you.

Fear: Antidepressants make you forget your problems rather than deal with them.

Fact: Antidepressants can’t make you forget your problems, but they may make it easier for you to deal with them. Being depressed can distort your perception of your problems and sap you of the energy to address difficult issues. Many therapists report that when their patients take antidepressants, it helps them make more progress in counseling.

Fear: Antidepressants change your personality or turn you into a zombie.

Fact: When administered correctly, antidepressants will not change your personality. They will help you feel like yourself again and return to your previous level of functioning. (If a person who isn’t depressed takes antidepressants, they do not improve that person’s mood or functioning.) Rarely, people experience apathy or loss of emotions while on certain antidepressants. When this happens, switching to a different antidepressant may help.

Fear: Taking an antidepressant will make me gain weight.

Fact: Like all drugs, antidepressants have side effects, and weight gain can be a common one of many of them. Some antidepressants may be more likely than others to cause weight gain; others may actually cause you to lose some weight. If this is a concern, talk with your doctor.

Fear: If I start taking antidepressants, I’ll have to take them for the rest of my life.

Fact: Most people who take antidepressants need to take them continuously for six to nine months – not necessarily a lifetime. Once an antidepressant gets depression under control, you should work with your doctor to decide when to stop your medication and then decrease your dose gradually. Discontinuing them suddenly may cause problems such as headaches, dizziness, and nausea.

Fear: Antidepressants will destroy my sex life.

Fact: Antidepressants can have an effect on sexual functioning. The problem is usually an inability to achieve orgasm rather than a lack of desire. But because depression itself decreases libido, a medication that eases depression may improve your sex life. As with other side effects, certain antidepressants may be more likely than others to cause sexual problems.

Fear: Antidepressants are expensive and aren’t covered by insurance.

Fact: Antidepressants are usually covered by insurance plans with prescription drug coverage. The cost of antidepressant therapy varies widely, depending on the dosage, the drug you are taking, and whether it is available as a generic. Even without insurance coverage, it is possible to purchase a generic antidepressant for as little as $15 per month.

Fear: Taking an antidepressant is a sign of weakness.

Fact: Like medical conditions such as diabetes or high cholesterol, major depression is a condition that often responds to medication.When depression interferes with your ability to function normally, seeking treatment is not a sign of weakness. It’s a sign of good self-care.

Fear: Antidepressants increase the risk of suicide.

Fact: Studies in recent years have raised concerns that antidepressants may raise the risk of suicide among children, adolescents, and young adults. For example, a 2009 review in the British Medical Journal (BMJ) analyzed 372 studies involving nearly 100,000 people who were taking antidepressants. It found that compared to placebo, use of antidepressant drugs was associated with a small increased risk for suicidal thoughts in some children and young adults, have no effect on suicide risk among those 25 to 64, and reduce risk in those 65 and older.

In 2004, the FDA required manufacturers of antidepressants to revise their labels to include a black box warning statement about these risks.

Other studies paint a different picture. A 2006 study published in PLoS Medicine suggests that the use of antidepressants has saved thousands of lives. Data show that the U.S. suicide rate held fairly steady for 15 years prior to the introduction of the widely used antidepressant fluoxetine (Prozac) and then dropped steadily over 14 years while sales of Prozac rose. The research team found the strongest effect among women.

The bottom line: Regardless of your age or sex, it’s important to see a doctor immediately if you have suicidal tendencies or witness them in others.

source:web MD

Food Addiction May Have Impact on the Brain

Study Shows People With Food Addictions Have Same Brain Activity Patterns as People With Other Addictions.
person biting into a large burger

The brains of people with food addiction appear to behave like those of people with dependence on alcohol or drugs, according to new research.

”People who report symptoms of addictive-like eating behavior also appear to show the same pattern of brain activity as we would see in other addictions,” says researcher Ashley N. Gearhardt, a clinical psychology doctoral student at Yale University.

Her study is published online in the Archives of General Psychiatry.

The researchers believe the study is the first to link addictive eating with a specific brain activity pattern.

The study results suggest that some obese people may be better served with addiction treatment than with traditional obesity treatments, says Mark Gold, MD, an addiction expert at the University of Florida, Gainesville, who reviewed the study results for WebMD.

Food Addiction and Brain Activity

With one-third of American adults obese, Gearhardt and her colleagues wanted to explore the theory that addictive processes may be involved in the development of obesity.

For the study, the researchers did a complete evaluation on 39 women, average age about 21. Their average body mass index (BMI) was 28 (25 and above is termed overweight). They ranged, however, from lean to obese. All had enrolled in a program to help people get to and maintain a healthy body weight.

The researchers used the Yale Food Addiction Scale to measure addictive eating and gave each woman a score. The scale has 25 items and asks about eating behaviors such as loss of control.

Next, the researchers used functional MRIs (fMRI), which are capable of measuring tiny metabolic changes that take place in the active parts of the brain.

The fMRIs were done when the women drank a tasty chocolate milkshake and a tasteless drink. They were also done when the women were shown pictures of the milkshake and a glass of water.

When the women looked at the picture of the milkshake, the food addiction scores correlated with greater activation in areas of the brain that help encode the motivational value of certain stimuli in response to food cues. Activation in these areas has been linked to food cravings, for instance, Gearhardt tells WebMD.

In response to their anticipation of food, women with the higher food addiction scores, compared to those with lower scores, had more activity in two areas of the brain. These two areas are involved in decision-making, control of behaviors, and learning relationships between stimuli and responses.

When drinking the milkshake, women with higher food addiction scores showed less activation in the area of the brain that is concerned with being able to inhibit a behavior. It indicates these women were less able to control their actions.

The brain patterns found in people with high addictive food scores, Gearhardt tells WebMD, are very similar to what is seen with other addictions.

“For people who are saying, ‘I feel addicted to food, I can’ stop,’ the same brain patterns appear to be involved,” she says.

No link was found between the scores on the test and body mass index. Some lean women had high scores. Gearhardt says that suggests evaluating food addictive behaviors in lean people may help identify those at risk for later weight gain or eating problems.

The study is an important one, says Gold, who is the Donald R. Dizney Eminent Scholar and Distinguished Professor at the University of Florida.

“There is a considerable amount of controversy about what a food addiction is,” he says. “One of the reasons this study is so important is they are correlating findings with brain changes rather than someone’s belief.” The new research used a validated scale to assess the addiction objectively, he says.

To him, the bottom line of the new research is this: “The more food addicted, the more likely you are to have changes in the brain that look as though you are on a drug.”

The study may help explain why some obese people who obtain treatments that focus on the physical — such as weight loss surgery — aren’t helped, Gold tells WebMD.

For those who are food addicted, paying attention to food cues is crucial, Gearhardt says. “Monitor what triggers for you your out-of-control behavior.”

Changing your environment in a food-obsessed society is difficult, she says, but not impossible. If driving past your favorite bakery on your way to work is too much temptation, for instance, find a new route to work, she says.

source: webMD

Bone: from a reservoir of minerals to a regulator of energy metabolism

Besides locomotion, organ protection, and calcium–phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secretion, insulin sensitivity, and pancreas β-cell proliferation) in the regulation of energy metabolism is described. Then, the connections between insulin signaling on osteoblasts and the release of uncarboxylated osteocalcin during osteoclast bone resorption through osteoprotegerin are reported. Finally, the understanding of this new bone endocrinology will provide some insights into bone, kidney, and energy metabolism in patients with chronic kidney disease.

source: kidney international