Colon cancer warning signs

A lot of patients suffering from colon cancer might well present no symptoms or signs during the earliest stages of the condition. When symptoms do eventually present, they can be many and varied, and can very much depend upon the size of the affliction, how far it has spread and also its actual location. It might be that some symptoms that present are as a result of a condition other than cancer itself, ranging from irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and occasionally diverticulosis. Also, such problems as abdominal pain or swelling can be symptomatic of colon problems and may well require further investigation.

You may also notice that, upon going to the lavatory, you have some blood in your stools, and this can be a symptom of cancer. It can, however, also be indicative of other conditions and problems. For example, the kind of bright red blood that you may see on your toilet tissue could be as a result of hemorrhoids or anal fissures. It should also be remembered that various food items can also result in red-colored stools, and these include beetroot and red liquorice. Some medications can also be culprits, and some can also turn the stools black-including iron supplements. Irrespective, any sign of blood or change in your stools should prompt you to seek advice from your GP, as it is always best to be sure that it is not a sign of a more serious condition, and with any cancer,early detection and treatment is essential to a successful recovery.

You should also note-if you are currently concerned-any change in the regularity of your stools-including whether or not they are more thin or irregular than usual-especially over a period of several weeks. Also, be mindful if you have diarrhea for several days in a row or, conversely, constipation.

You might also experience pain in your lower abdomen-including a feeling of hardness. You may also experience persistent pain or discomfort in your abdominal region, and this can include wind and cramps. You may also get the sensation that, when evacuating your bowels, that the bowel doesn’t empty fully. Also, if you have an iron deficiency (or anemia), it may be an indication that there is bleeding in your colon. Also, as in most cases and types of cancer, you should seek medical advice immediately if you experience any sudden and unexpected or unexplained weight loss, as this is one of the principal red flags. Also be aware of more vague, seemingly incidental symptoms, such as fatigue. IF you have a couple of symptoms and also feel fatigued for days in a row inexplicably, then this is also another warning sign and you should seek medical advice. It is important not to panic, but just to be aware of what might be going on.

Remember, cases of colon cancer account for around 90% of all cases of intestinal cancers, and also account for more deaths every year of men and women from cancer. Early treatment is an absolute must.

Colon cancer warning signs

A lot of patients suffering from colon cancer might well present no symptoms or signs during the earliest stages of the condition. When symptoms do eventually present, they can be many and varied, and can very much depend upon the size of the affliction, how far it has spread and also its actual location. It might be that some symptoms that present are as a result of a condition other than cancer itself, ranging from irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and occasionally diverticulosis. Also, such problems as abdominal pain or swelling can be symptomatic of colon problems and may well require further investigation.

You may also notice that, upon going to the lavatory, you have some blood in your stools, and this can be a symptom of cancer. It can, however, also be indicative of other conditions and problems. For example, the kind of bright red blood that you may see on your toilet tissue could be as a result of hemorrhoids or anal fissures. It should also be remembered that various food items can also result in red-colored stools, and these include beetroot and red liquorice. Some medications can also be culprits, and some can also turn the stools black-including iron supplements. Irrespective, any sign of blood or change in your stools should prompt you to seek advice from your GP, as it is always best to be sure that it is not a sign of a more serious condition, and with any cancer,early detection and treatment is essential to a successful recovery.

You should also note-if you are currently concerned-any change in the regularity of your stools-including whether or not they are more thin or irregular than usual-especially over a period of several weeks. Also, be mindful if you have diarrhea for several days in a row or, conversely, constipation.

You might also experience pain in your lower abdomen-including a feeling of hardness. You may also experience persistent pain or discomfort in your abdominal region, and this can include wind and cramps. You may also get the sensation that, when evacuating your bowels, that the bowel doesn’t empty fully. Also, if you have an iron deficiency (or anemia), it may be an indication that there is bleeding in your colon. Also, as in most cases and types of cancer, you should seek medical advice immediately if you experience any sudden and unexpected or unexplained weight loss, as this is one of the principal red flags. Also be aware of more vague, seemingly incidental symptoms, such as fatigue. IF you have a couple of symptoms and also feel fatigued for days in a row inexplicably, then this is also another warning sign and you should seek medical advice. It is important not to panic, but just to be aware of what might be going on.

Remember, cases of colon cancer account for around 90% of all cases of intestinal cancers, and also account for more deaths every year of men and women from cancer. Early treatment is an absolute must.

Heat can help chemotherapy work better

Cancer patients whose tumors are targeted with heat treatment as well as chemotherapy are more likely to stay alive and cancer-free for longer than those who receive only chemotherapy, researchers said on Tuesday.

The finding suggests it may be possible to cut the dose of chemotherapy drugs by using heat, although more research is needed to establish this, they said.

German researchers looking at cancers in soft tissues such as muscle, fat and tissue around the joints, found that heat treatment more than doubled the proportion of patients whose tumors responded to chemotherapy.

mportantly, the process did not increase the harmful effects of chemotherapy treatment.

"We expect our findings will encourage other researchers to test the approach in other locally advanced cancers," said Rolf Issels, a professor of medical oncology at the University of Munich in Germany.

"Targeted heat therapy has already shown promise in recurrent breast and locally advanced cervical cancer in combination with radiation, and studies combining it with chemotherapy in other localized tumors such as those in the pancreas and rectum are ongoing."

Heat therapy for cancer involves a technique known as regional hyperthermia, which uses focused electromagnetic energy to warm the tissue in and around the tumor to between 40 and 43 degrees Celsius (104 to 109.4 degrees Fahrenheit).

The heat not only kills cancer cells, but also seems to make chemotherapy work better by making cancer cells more sensitive, Issels said. It also improves blood flow, allowing chemotherapy to be more effective.

Issels said his findings, presented at the ECCO-ESMO European cancer congress in Berlin, showed that soft tissue sarcoma patients receiving the targeted heat therapy plus chemotherapy "fared better on all outcome measurements."

"Almost three years after starting treatment, they were 42 percent less likely to experience a recurrence of their cancer at the same site or to die than those who were getting chemotherapy alone," he said.

The average length of time that patients remained disease free was 32 months in the group that got both treatments, compared with 18 months in the group that got chemotherapy alone — an improvement of 30 percent.

Issels said the equipment and specialist knowledge to be able to offer such heat therapies is only currently available in a handful of clinics and hospitals in Germany, the Netherlands, Switzerland, Norway and the United States.

But he urged cancer doctors to take note.

"The clear results of this trial show that the field has now matured to the point where we must step up efforts to explore its potential to offer an entirely new way of treating locally advanced disease in several major cancers," he said.

Drug makers chase cancer stem cells

As evidence implicating stem cells in cancer mounts, drug makers are taking notice. GlaxoSmithKline (GSK) in December formed a strategic alliance worth up to $1.4 billion with OncoMed Pharmaceuticals, of Redwood City, California. The deal gives GSK an option to license four of OncoMed's antibody candidates developed to target cancer stem cells, one of which is scheduled to enter clinical trials in June.

The GSK-OncoMed pact is the first major deal focused on cancer stem cell R&D, which is undergoing explosive growth. John Bates, the director of Biopharm Reports, in Cambridge, UK, says the number of companies devoted to this research has grown from 17 in April 2007 to nearly 40 today. What's more, patents covering developments in cancer stem cells doubled to about 70 in 2007, he adds. The problem is that not everyone even believes that targeting cancer stem cells will yield therapeutic benefits.

George Schreiner, CEO with Raven Biotechnologies in San Francisco, attributes the burst of commercial interest to recent evidence of cancer stem cells in solid tumors. Scientists have suspected since the 1950s that the cells play a role in blood tumors, such as acute myeloid leukemia, but their existence in solid tumors became evident only in 2003. That's when Michael Clarke, currently associate director of Stanford University's Institute for Stem Cell and Regenerative Medicine, and his then post-doc, Mohamed Al-Hajj, claimed to find cancer stem cells in breast tumors. The cells had two markers that are now synonymous with cancer stem cells: high expression of the antigen CD44 and low expression of antigen CD24. Isolated on the basis of these markers, the human cells were cultured and introduced into immunocompromised mice. Clarke and Al-Hajj found that only a few of the cells could spawn aggressive, metastatic tumors in the animals. Those findings bolstered a theory that solid tumors arise from a small population of cancer stem cells that, like normal stem cells, have the capacity for self-renewal. Clarke and his colleague Max Wicha, the director of the University of Michigan Comprehensive Cancer Center, founded OncoMed to pursue clinical opportunities in cancer stem cells in 2004. They now sit on the company's scientific advisory board.

Findings in other laboratories have since suggested cancer stem cells exist in various tumors, including those of the brain, head and neck, prostate, and colon. Scientists further postulate that cancer stem cells resist current drug therapies and repair DNA after radiation treatment more efficiently than their differentiated, daughter cells. That explains why solid tumors often recur after treatment, Schreiner explains. "What happens is the stem cells survive and repopulate to form a new tumor," he says. "And because they transmit their resistance to daughter cells, the new tumors are much harder to treat." Some researchers now believe the only way to cure cancer is by killing the stem cells that give rise to it.

OncoMed is one of a handful of companies preparing to test compounds against cancer stem cells in the clinic. In the GSK deal, OncoMed receives an undisclosed, up-front payment in cash and equity investment, with $1.4 billion more tied to achieving milestones. Royalties on product sales would follow. OncoMed's lead candidate, a humanized monoclonal antibody (mAb) OMP-21M18, targets "a cancer stem cell pathway with broad applicability across multiple solid tumors," says Paul Hastings, the company's CEO.

Other companies preparing for clinical trials this year include Arius Research in Toronto, whose lead humanized IgG1 mAb targets a variant form of CD44 found in leukemia, breast, colon and prostate cancer cells. Also, Raven Biotechnologies has two mAbs in preclinical development: RAV17 (which targets the pancreatic assigned tumor marker PAN), which Schreiner says targets prostate as well as pancreatic cancer cells, and RAV18 (which targets ADAM-9), for colon and lung cancer. Raven is now preparing to merge with VaxGen, a San Francisco-based vaccine manufacturer, picking up needed cash reserves from a company with a depleted pipeline but plenty of manufacturing assets. Reflecting a broader trend in cancer drug development, most compounds targeting cancer stem cells are monoclonal antibodies, Bates says (see Table 1). MAbs predominate because they target antigens on the cell surface rather than processes inside the cell as small molecules do.

The chief safety concern with targeting cancer stem cells, Clarke warns, is that these mAbs might also attack normal stem cells that replenish damaged tissues. "The main thing is to ensure that we eliminate the malignant cancer stem cells only without affecting the normal stem cells," he says. "Whether we'll be able to do this is the billion dollar question that everyone wants to answer."

Meanwhile, as commercial entities grow up around it, skeptics question the validity of targeting cancer stem cells. Current thinking holds that a tiny population of stem cells can explain why cancers recur even when existing treatments kill off up to 99% of a given tumor. According to Bert Volgestein, a professor of oncology at Johns Hopkins University in Baltimore, tumors can be completely eradicated only if those small—and presumably drug-resistant—stem cell fractions are destroyed.

The tumor fraction contributed by stem cells ranges from a low of 0.1% to a high of 40%, and some reports have described tumors made entirely of stem cells. But Vogelstein also admits that if a tumor containing a large fraction of stem cells were almost completely eliminated by treatment, this would undermine the logic of targeting stem cells as the last, drug-resistant holdouts from which aggressive metastatic tumors would likely emerge refractive to treatment.
GSK's interest in OncoMed comes from a desperation "to tap into oncology space, an area in which it is particularly weak," says Sho Matsubara, an analyst with London-based Standard and Poor's Equity Research Division. Also, GSK's sales are assumed to decline in coming years, due to generic competition (Matsubara estimates a 7% drop annually for the next five years). It does have a compound of its own that may have shrunk breast tumors by attacking cancer stem cells. According to evidence described at the San Antonio Breast Cancer Symposium on December 17, six weeks' treatment with GSK's Tyverb (lapatinib), a small molecule used in conjunction with Xeloda (capecitabine) for late-stage breast cancer, slashed the number of stem cells by more than half among 30 women studied. Two-thirds of the women were reportedly cancer-free after follow-up treatment.

But others remain cautious as, in some instances, claims pointing to the existence of cancer stem cells have turned out to be wrong upon closer inspection. "More studies are needed to confirm that cancer stem cells were in fact targeted by Tyverb," Bates notes. "We need further evidence to show that cancer stem cells in humans have been fully characterized. And we need ways to demonstrate that a particular subpopulation of cells has been reduced by treatment," he notes.
Ultimately, the best evidence will come from more studies that show killing cancer stem cells improves patient survival, Bates says. For fast-moving cancers such as pancreatic tumors, the evidence may come sooner. In the case of slow-moving cancers, such as prostate, accumulating the necessary evidence could take more time, he points out.

Liver Tumours – Good & Evil is Decided by Two Signalling Pathways

he linking of two signalling pathways in the cells of liver tumours has a clear influence on their malignancy. Activation of the platelet-derived growth factor (PDGF) messenger molecule is decisive for this linking. This results related to the development of liver cancer was generated during a current project by the Austrian Science Fund FWF and has been published in the Journal Oncogene. When the signalling pathways in liver tumour cells have been linked together, these cells develop the characteristics of cancer stem cells, which are in principal resistant to chemotherapy. This new understanding of the signalling pathways involved unlocks potential for the future development of modified therapies.

The transformation of epithelial cells into mesenchymal cells can be either good or bad. It is good for embryonic development, inflammations and tissue regeneration. It is bad when this transformation, known as epithelial to mesenchymal transition (EMT), occurs in cancer cells, as the cancerous cells are then able to migrate into other tissues and form metastases.

SUPPRESSOR OR AGGRESSOR?
It was already understood that a signalling pathway of TGF-beta (transforming growth factor beta) was involved in EMT. However, as this messenger substance tends to hinder cell proliferation and also makes cells sensitive to the body's own defences, it was previously regarded as a tumour suppressor. But recent findings have shown that, when it occurs in cells that are already transformed, TGF-beta actually contributes to their aggressiveness. Until recently, it was not known how this happens.

A team headed by Prof. Wolfgang Mikulits from the Institute of Cancer Research at the Medical University of Vienna has now moved a great deal closer to better understanding these processes. The team discovered that, by activating the platelet-derived growth factor (PGDF), the signalling pathway of TGF-beta causes the accumulation of another messenger substance that had not previously been associated with the signalling pathway of TGF-beta: beta-catenin.

Prof. Mikulits explains: "PGDF forms a kind of bridge that links together two signalling pathways that were previously regarded as entirely independent. This discovery in itself was exciting. However, when we investigated the effect of beta-catenin further, we were astounded."

SLOW & RESISTANT
Beta-catenin was previously associated with an increased rate of cell division, or in other words, accelerated tumour growth. However, Prof. Mikulits' team observed entirely different cell behaviour in reaction to beta-catenin in cell cultures. "We found that beta-catenin actually slowed down the rate of cell division, which – in a tumour – is not a bad thing. However, it makes the cells unsuitable targets for chemotherapy. Cells containing beta-catenin also exhibited another characteristic. They were less susceptible to the natural defences in the body which eliminate cells that migrate from organs." In tumour cells, both these features – a lower division rate and resistance to defence mechanisms – are known to be typical properties of cancer stem cells. In other words, cells that migrate through the bloodstream and can create new tumours elsewhere in the body – metastases.

The linking of the signalling pathways of TGF-beta and beta-catenin by PGDF increases the aggressiveness of liver tumours and therefore offers a new point of attack for future liver cancer treatments. However, the results of this FWF project are already revealing ways in which the current treatment of liver cancer can be optimised. The accumulation of beta-catenin in cancer cells can be diagnosed before treatment is begun, which means that therapy could then be tailored to the aggressiveness of the tumour.

Listeria pathogen may be key to understanding cancer development

A research team including University of Central Florida Microbiology Professor Keith Ireton is using the bacterial pathogen Listeria Monocytogenes to understand the mechanisms of cell growth and cancer development.

In research published this month in the Journal of Biological Chemistry, the team found that a Listeria protein called InlB induces internalization and degradation of a human receptor known as Met. Met has been implicated in the development of some cancers.

Lisa A. Elferink at the University of Texas Medical Branch led the team. She and Ireton found that the ability of InlB to induce Met internalization and degradation requires a human protein called Cbl. If scientists could figure out how to control Cbl, such knowledge might lead to the development of drugs that induce the destruction of Met and are useful in treating Met-related cancers.

Ireton is an expert on Listeria monocytogenes, a cause of food poisoning. He has long studied how it enters into cells of the human body, and explains the mechanism in this month's issue of the journal Cellular Microbiology.

We found that Listeria actually provokes human epithelial cells (cells lining the small intestine) into ingesting bacteria, Ireton said.When Listeria contacts an epithelial cell, the bacterium causes changes in the cell's cytoskeleton that allow the cell to swallow up the bacterium. We discovered that a human protein called CrkII plays a critical role in stimulating internalization of Listeria by somehow controlling the cytoskeleton.

Listeria is a potentially deadly pathogen, causing abortions in pregnant women and meningitis in those with compromised immune systems, resulting in about a 25 percent mortality rate.
The findings are important in helping to understand and control the spread of bacteria that are a cause of potentially fatal food poisoning. Ireton said the bacteria can live outside animal hosts. Sources include dead plant matter, fruits and vegetables, unpasteurized diary products and meats that have not been properly cooked. Pregnant women and people with compromised immune systems are particularly susceptible.

To avoid contamination, Ireton suggests cooking all meats thoroughly, avoiding dairy products that are not pasteurized and washing all fruits and vegetables thoroughly before consumption.

Spicy food can prevent cancer

Here is some spicy news for cancer patients.

In a major breakthrough, it has been revealed that tumours can be killed without any side effects though a compound called Capsaicin, an active component in chilli that makes spicy food hot and generates the heat in muscle strain remedies.

The revelation may be crucial in the development of a new generation of cancer drugs, a top scientist has said. Capsaicin is commonly used as an active ingredient in muscle rub creams and the treatments for psoriasis.

The tests, which were conducted by a research team at the Nottingham University led by Dr Timothy Bates, have shown positive results -- killing a variety of tumour cells like the pancreatic cancer, which is one of the most difficult to treat and has a five-year survival rate of less than one per cent. "We appear to have discovered a fundamental weakness with all cancer cells. Capsaicin specifically targets cancerous cells. When released onto cancer cells, capsaicin attacks the mitochondria in the cell, which is responsible for generating ATP, the major energy-producing chemical in the body. Capsaicin specifically binds to the protein within the mitochondria of tumour cells and triggers apoptosis, the process of natural cell death," Dr Bates said.

The fact that capsaicin, part of a group of food compounds called vanilloids, was a common part of the diet in many countries would dramatically reduce the number of regulatory hurdles that any anti-cancer drug would have to overcome, he added.According to Dr Bates, the findings probably explained why people in countries like India, who traditionally eat a diet which is very spicy, tend to have lower incidences of many cancers that are prevalent in the Western world.The discovery could lead to the production of drugs to cure a variety of cancers at a fraction of the �410 million cost of developing conventional medicines, as capsaicin is already consumed daily by millions of people.

Using viruses to fight cancer

Contract the common cold to fight cancer � does it sound loony?

Not really, not if cutting-edge research being done by British scientists were to see results. They are readying to launch human trials of the technique of killing tumours by infecting them viruses like that of common cold, reports The Guardian, London.

Currently, there are two weapons in the war against Big C � radiotherapy and chemotherapy. If successful, virotherapy could emerge as the third arm in the war.

Leonard Seymour, professor of gene therapy at Oxford University, will lead the trials later this year. 'In principle, you have got something that could be many times more effective than regular chemotherapy,' he said.

Those who have seen a loved one undergo chemotherapy, or went through the ordeal themselves, know how debilitating the process is. Virotherapy, on the other hand, promises none of it.

The new therapy uses cancer's own working � of suppressing the body's local immune system � as its Achilles heel. Viruses find tumours a great nesting place since there is no immune system to stop them from replicating. What's more, it's not like a great amount of the virus needs to enter the tumour. 'They replicate, you get a million copies in each cell and the cell bursts and they infect the tumour cells adjacent and repeat the process,' Prof Seymour was quoted by The Guardian as saying. He should know, for he has been working with viruses that kill cancer but don't harm healthy tissue.

It's been known for some time that viruses can kill tumour cells; in fact scientific journals have published some aspects of the work. In America viruses have been directly injected into tumours but this technique has one major flaw: it will not work if the cancer is either inaccessible or spread throughout the body.

Where Prof Seymour's solution differs is to mask the virus a la a stealth bomber, away from the radar of the body's immune system which will seek and destroy it otherwise. His technique allows the viruses to work like chemotherapy drugs � reach the tumour through the blood stream. This is done by giving the virus a polymer coat after some chemical modifications.
The virus replicates after infecting the tumour, but hearteningly the copies lack the chemical modifications. The challenge is to contain them within the tumour, otherwise they will be finished by the immune system.

Preliminary research on mice has shows the virus working on tumours that are otherwise resistant to standard cancer drugs.

Virotherapy is expected to be particularly useful in the case of secondary cancers, known as metastases.

The human clinical trials are expected to use two viruses: adenovirus, which gives you a cold-like illness if you have contracted it, and vaccinia, which causes cowpox. The viruses will be uncoated during the trials, delivering them locally to liver tumours in order to find out if the treatment works in humans. The trials, later involving polymer-coated viruses, are expected to take several years.

Researchers hope that some day viruses will become an important part of the arsenal against cancer, a disease that has dogged the human race for centuries.

Cancer stem cells similar to normal stem cells thwart anti-cancer agents

Current cancer therapies often succeed at initially eliminating the bulk of the disease, including all rapidly proliferating cells, but are eventually thwarted because they cannot eliminate a small reservoir of multiple-drug-resistant tumor cells, called cancer stem cells, which ultimately become the source of disease recurrence and eventual metastasis.

Now, research by scientists at the University of Pittsburgh School of Medicine suggests that for chemotherapy to be truly effective in treating lung cancers, for example, it must be able to target a small subset of cancer stem cells, which they have shown share the same protective mechanisms as normal lung stem cells. They presented this ground-breaking research at the Tissue Engineering and Regenerative Medicine International Society (TERMIS) North American Chapter meeting in Toronto.

The University of Pittsburgh researchers, led by Vera Donnenberg, Ph.D., assistant professor of surgery and pharmaceutical sciences, University of Pittsburgh Schools of Medicine and Pharmacy, used cell surface markers and dyes to identify cancer stem cells as well as normal adult stem cells and their progeny in samples obtained from normal lung and lung cancer tissue samples. The researchers identified a very small, rare set of resting cancer stem cells in the lung cancer samples that looked and behaved much like normal adult lung tissue stem cells. Both the cancer and normal stem cells were protected equally by multiple drug resistance transporters, even if the bulk of the tumor responded to chemotherapy.

According to Dr. Donnenberg, the very fact that cancers can and do relapse after apparently successful therapy indicates the survival of a drug-resistant, tumor-initiating population of cells in many types of refractory cancers. "Because of the similarities between the way that normal stem cells and cancer stem cells protect themselves, cancer therapies have to be designed specifically to target cancer stem cells while sparing normal stem cells," she explained.

Cheap, Safe drug shows potential to kill cancer cells

Recent tests have shown that an inexpensive drug may be able to kill cancer cells in humans. Dichloroacetate, a drug generally used to treat rare metabolic disorders, has shown the potential to assist in the treatment of brain, lung, and breast cancers, researchers at the University of Alberta in Edmonton, Canada say.

Dr. Evangelos Michelakis of the University of Alberta in Edmonton, Canada found that that DCA causes tumor regressions in animals with human cancers. Testing showed that DCA attacked cancer cells but did not attack healthy cells.

The researchers and the Alberta Cancer Board and Capital Health do not advise the use of DCA to treat cancer yet, as clinical trials for the drugs use to treat cancer have not been performed yet.

Structure of a typical animal cell. The blue capsule-like structure containing the yellow ribbon-like membrane is the mitochondria (Colors are schematic, not real).Unlike healthy cells, cancerous cells do not convert food molecules into energy in the mitochondria. Instead, they rely on a process known as glycolysis, which takes place in the main body of the cell, while the mitochondria are "shut down", researchers believe possibly due to the lack of oxygen supply to cells in the middle of a tumor.

This means that another key function of the mitochondria - to activate an abnormal cell's self-destruct mechanism, apoptosis - is also blocked.

When Dichloroacetate (DCA) enters a cancer cell, it restarts the mitochondria which in turn activate apoptosis, and the cancerous cell destroys itself.

DCA is known to be relatively safe, although pain, numbness and gait disturbances may occur. The drug is also expected to be cheaper to manufacture than other drugs since there is no patent for it.