A Landmark Study by an Old Friend in India

Dear friends,
Not only I but all those who have known Dr. Santasabuj Das during his stay at SGPGI, Lucknow, would be proud of his landmark findings that have just appeared in a very prestigious journal, Proceedings of National Academy of Sciences (PNAS). Going down memory lane, I can recall those times very well, when I just had started as a Ph.D. student in the Department of Gastroenterology and was going through rotations in various laboratories in the Department of Immunology, a major collaborating department at the Institute, where most of GI fellows and Ph.D students used to be trained for their laboratory based projects those days. Dr. Santasabuj Das (fondly known as Dr. Das) also had started his postdoctoral medical residency in the Department of Immunology at the same time. I guess everyone known to him during that time would agree with me in recalling him as a voracious reader, often found lost in books and journals in library reading almost everything, little-shy, too inquisitive about everything while in seminars and classes, and may be always restless (may be it was constantly ongoing quest for knowledge inside him that often appeared on his face). He soon realized that his destiny was in laboratory science and left for NCBS and subsequently to the US, to learn more and more about what he had always been passionate about. Now after so many years later, here he is back with such a great work, so much relevant to the people in India, Bangladesh, and many other tropical countries.
http://www.pnas.org/content/early/2011/02/03/1016180108.abstract

We all have heard of typhoid fever, which is a common illness in tropical countries. It is caused by bacteria Salmonella Typhi. Please do not mistake it with Salmonella Typhimurium which is more commonly found bacteria and causes enteric diseases, also a common cause of food adulteration in western countries where they use packed food especially vegetables and eggs as opposed to tropical countries where still fresh and seasonal vegetables are in fshion mainly due to lack of uniturrupted power supply and equipments to  freeze foods. Anyways, in the age of antibiotics, management of typhoid is not a big problem, but if not treated in time or infected with a version of bacterium which is resistance for commonly used antibiotics, it can lead to serious consequences. There is another interesting angle to Salmonella Typhi infection – 1% of all those who have ever been infected with Salmonella Typhi become chronic career. It means 1% of all infected people will still harbor bacteria for years and decades though with no symptoms. This bacteria travells all the way to the gallbladder where it finally makes it home as it gets to eat its favourite foods available in the form of bile salts and resides silently and does not apparantly harm to the person. There is a famous study conducted in NewYork City in early 20^th Century, where a lady known as Mary Mallon, more notoriously known as "Typhoid Mary" who was  a chronic career Salmonella typhi, infected ~53 people.  

Anyways, I also have some connection with all this, as a major part of my Ph.D. thesis work was focused on the role of chronic Salmonella infection in gallbladder cancer. There are a group of physicians and scientists in India (where gallbladder cancer is more frequently found), including Dr. Gourdas Choudhuri (my Ph.D. advisor) and Dr. V. K. Kapoor at SGPGI, Lucknow, and Dr. V.K. Shukla at Banaras Hindu University, believe and have some published evidences that it is chronic infection of gallbladder with Salmonella Typhi, which along with inflammatory events due to long term persistence of gallstones (which is another associated factor with gallbladder cancer) that results in early carcinogenic events in the gallbladder. However, I must say that this hypothesis needs more solid evidences and may be a more direct demonstrations in an animal model which has been so far not feasible by all available laboratory methods. However, coming back to Dr. Das’ contribution, in his report he has very nicely described a role of an adhesion protein present in Salmonella, which was not known so far, could be very helpful in designing a new type of vaccine which can protect against Salmonella infection much more effectively than existing vaccines.

By the way, this article has also been selected by "Nature" as one of the most important studies came this week:
http://www.nature.com/nature/journal/v470/n7334/full/470308d.html?WT.ec_id=NATURE-20110217 

Advances in Liver Cancer Therapy

Liver Cancer  is the sixth most common cancer in the world in terms of incidence, accounting for approximately 630 thousand new cases per year. In addition, Liver Cancer is the third most common cause of cancer death. The greatest risk factors for HCC are the chronic infections caused by hepatitis B and C viruses, which increase the risk of developing the cancer by about 20 times. The standard treatment in the early stages of the disease, such as surgical resection and liver transplantation, are able to cure a minority of patients. Unfortunately, most cases of Liver Cancer are diagnosed in advanced stages, making these cancers beyond the scope of any treatment. In these advanced stages, systemic treatments are commonly used. Unfortunately, chemotherapy with conventional cytotoxic agents is ineffective and does not seem to modify the natural history of disease. Treatment options for patients with advanced liver cancers are extremely limited, but the identification of signaling pathways, in other words identification of those proteins which are specifically involved with initiation and progression of the liver cancer, and the recognition of the role of these pathways that include these specific proteins in the pathogenesis of the disease resulted in the development of drugs directed at specific therapeutic targets. One such drug is Sorafenib, a kinase inhibitor with antiangiogenic and antiproliferative properties. In conclusion, Sorafenib has demonstrated survival benefits in patients with advanced Liver cancer, thus representing a new standard reference for systemic treatment in these cases. To understand better about molecular targeted therapy or specific therapeutic target I will simplify it here for those who are not aware of it: 

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. Because scientists often call these molecules “molecular targets,” targeted cancer therapies are sometimes called “molecularly targeted drugs,” “molecularly targeted therapies,” or other similar names. By focusing on molecular and cellular changes that are specific to cancer, targeted cancer therapies may be more effective than other types of treatment, including chemotherapy and radiotherapy and less harmful to normal cells.

Many targeted cancer therapies have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of specific types of cancer. Others are being studied in clinical trials (research studies with people), and many more are in preclinical testing (research studies with animals).

Targeted cancer therapies are being studied for use alone, in combination with other targeted therapies, and in combination with other cancer treatments, such as chemotherapy.

Molecular Targeted Therapies are likely to prove as best treatment modalities in future not only for Liver but most of the cancer types. Though it is still in early stage and cost is a major issue. Lets hope for the best.   

HEF1/NEDD9: a missing link to Colorectal Cancer progression

Colorectal cancer is the second leading cause of cancer related death in the United States and equally a big problem in many parts of the world. The promise of personalised medicine is now a clinical reality, with colorectal cancer genetics at the forefront of this next major advance in clinical medicine. This is no more evident than in the recent advances in testing of colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor. Today an important publication came online that found HEF1 also known as NEDD9 as one of the important proteins that regulate tumor progression in colorectal cancer. Interestingly, for last 5 years or so I have been working on the same molecule and other members of this protein family commonly known as Cas family proteins.
http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2010632a.html


      Though, authors' claim about HEF1 being an attractive drug target in colorectal cancer is little misleading for those who are not aware of the biology of the protein. HEF1 does not have enzymatic activity, thus can not be targeted by conventional cancer therapeutics. However, other proteins which are part of same signaling network which encompasses HEF1 and are known drug targets, can well be targeted to disrupt to treat the colorectal cancer progression. I think it is important to mention here my own recently published work which describes the potential of HEF1/NEDD9 being used as predictive biomarker for multi-tyrosine kinase inhibitor therapy in other cancers:
 http://cancerres.aacrjournals.org/content/70/21/8907.short?rss=1


      My hunch is that HEF1 expression level in colorectal cancer  is going to prove as an important predictor of therapeutic response with regard to conventional chemotherapeutic agents as well as molecular targeted therapies either successfully being used in clinic or those that are still being explored in clinical trials. I wish to thank this team of researchers for such a nice work, which I am sure will attract attention of translational researchers to explore it further with regard  to colorectal cancer.

 For those who wish to know more about basic facts of colorectal cancer, please go to:
http://www.cancer.gov/cancertopics/factsheet/cancer-advances-in-focus/colorectal

Liver Cancer

First critic I received is from a close family friend. She does not have science background, so she was quite disappointed after going through my first blog as it was full of jargons. I really thank her for pointing out it because one of the main reasons to start this blog is to educate people about recent advances in biomedical sciences, which may include people from other walks of life not only those who are in science. So here is some basic information about liver cancer:    

What is liver cancer and what causes it:

Most commonly found liver cancer is Hepatocellular carcinoma. This type of cancer occurs more often in men than women. It is usually seen in people ages 50 - 60.

The disease is more common in parts of Africa and Asia than in North or South America and Europe.

Hepatocellular carcinoma is not the same as metastatic liver cancer, which starts in another organ (such as the breast or colon) and spreads to the liver.

In most cases, the cause of liver cancer is usually scarring of the liver (cirrhosis). Cirrhosis may be caused by:

·         Alcohol abuse (the most common cause in the United States)

·         Certain autoimmune diseases of the liver

·         Diseases that cause long-term inflammation of the liver

·         Hepatitis B or C virus infection

·         Too much iron in the body (hemochromatosis)

Patients with hepatitis B or C are at risk for liver cancer, even if they do not have cirrhosis.

Symptoms

·         Abdominal pain or tenderness, especially in the upper-right part

·         Easy bruising or bleeding

·         Enlarged abdomen

·         Yellow skin or eyes (jaundice)

Signs and tests

Physical examination may show an enlarged, tender liver.

Tests include:

·         Abdominal CT scan

·         Abdominal ultrasound

·         Liver biopsy

·         Liver enzymes (liver function tests)

·         Liver scan

·         Serum alpha fetoprotein

Some high-risk patients may get periodic blood tests and ultrasounds to see whether tumors are developing.

Treatment

Aggressive surgery or a liver transplant can successfully treat small or slow-growing tumors if they are diagnosed early. However, few patients are diagnosed early.

Chemotherapy and radiation treatments are not usually effective. However, they may be used to shrink large tumors so that surgery has a greater chance of success.

Sorafenib tosylate (Nexavar), an oral medicine that blocks tumor growth, is now approved for patients with advanced hepatocellular carcinoma.

Support Groups

You can ease the stress of illness by joining a support group with members who share common experiences and problems. See:

·         Cancer - support group

·         Liver disease - support group

Expectations (prognosis)

The usual outcome is poor, because only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery.

If the cancer cannot be completely removed, the disease is usually fatal within 3 - 6 months. However, survival can vary, and occasionally people will survive much longer than 6 months.

Complications

·         Gastrointestinal bleeding

·         Liver failure

·         Spread (metastasis) of the carcinoma

Calling your health care provider

Call your health care provider if you develop persistent abdominal pain, especially if you have a history of any liver disease.

Prevention

Preventing and treating viral hepatitis may help reduce your risk. Childhood vaccination against hepatitis B may reduce the risk of liver cancer in the future.

Avoid drinking excessive amounts of alcohol. Certain patients may benefit from screening for hemochromatosis.

If you have chronic hepatitis or known cirrhosis, periodic screening with liver ultrasound or measurement of blood alpha fetoprotein levels may help detect this cancer early.

References

National Cancer Institute. Adult primary liver cancer treatment PDQ. Updated May 22, 2009.

Roberts LR. Liver and biliary tract tumors. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 206.

Latest Research Reports a Driver of Metastasis in Liver Cancer

Today I will be completing exactly 13 years of my Bio-medical research career. During all these years, I have been too busy doing experiments, writing original manuscripts and reviewing other’s works.  Earlier there was no medium to express our minds informally, especially for an early career scientist like me. Now, with increasing popularity of using blogs as a tool to communicate and propagate one’s ideas in all the spheres of life such as Art, Literature, Politics etc., I have realized to take advantage of this medium to express my opinion about ongoing biomedical research efforts especially in cancer biology which is my area of expertise. Today I am sharing a very exciting report that just appeared last week. This group of scientists based at several institutes in USA, China, and Canada found out a new splice variant of a gene called  carboxypeptidase E gene (CPE), which was found to drive metastasis in liver cancer. I am sure this news has major significance for most of us who work in the area of cancer biology because metastasis is a major cause of mortality in cancer patients. However, in spite of all the recent advancements in the field, mechanisms governing the metastatic process remain elusive. Hope you will find it interesting:

http://www.jci.org/articles/view/40433