As I have mentioned in my previous post there are multiple reasons for getting cancer. We can add diet, smoking, alcohol, viruses, ageing, hormones, polyphenols, benzene, toxins, radiation etc to the list which can contribute in causing cancer.
But to change the perspective let me introduce the concept of apoptosis.
Apoptosis is programmed cell death. To give an example the skin which you have today is not the same as 21 days back. Skin gets new cells every 21 days. Similarly the mucosa in our mouth and intestine changes every day. The old cells die and new ones take their place. The old ones die a planned, programmed death known as apoptosis.
If the cell refuses to die for any reason it becomes a problem. We need a healthy balance between death and birth of new cells in the body.
Apoptosis also plays very important role in our growth. Growth of the baby from single cell to a new born. From new born to infant and from infancy to teenager. At all this growth periods apoptosis plays a very crucial role of controlled, structured, beneficial growth.
Cancer cells become immortal by avoiding apoptosis. Many genes play a role in this apoptosis game. p53, BCL, TRAIL pathway etc. There are many drugs being developed to promote apoptosis of cancer cells.
To just give a philosophical touch...........cells which become too selfish and forget that they have to reside inside an organism become malignant, cancerous. They evade apoptosis but unfortunately kill the body in which they reside. They forget that their selfishness has to be balanced with the survival of the whole organism/body..
Does it strike a chord?
Thursday, April 18, 2013
Wednesday, April 10, 2013
19 Year Old With Chronic Myeloid Leukemia And Kidney Failure
Last year 3 new drugs got approved for Chronic Myeloid Leukemia. They are Bosutinib, Ponatinib and Omacetaxine. Chronic Myeloid Leukemia (CML) has been the poster child for development of new targeted therapy. The hype started with Imatininb (Gleevec) which targeted the BCR-ABL translocation, one responsible for driving CML. Apart from above mentioned drugs we also have Nilotinib and Dasatinib.
Ponatinib is a second generation tyrosine kinase inhibitor while as rest all are first generation. Omacetaxine is an inject-able agent against protein synthesis. Ponatinib and Omacetaxine are also effective against the tough acquired mutation called T315I.
As I read about the progress being made I am reminded of a case which i had encountered few years back.
A 15 year old boy in Jan 2005 presented with weakness, etc.
Feb 2005 Hb-12.5 gm%, WBC 52,000. ( No comment on blast cells etc.)
Serum Creatinine 2.1. He was evaluated by physicians and nephrologist.
He was diagnosed to have Ig A Nephropathy with Chronic renal insufficiency.
Biopsy report reads -Mesangioproliferative glomerulonephritis.
For one year he was managed as Nephrotic patient only.
March 2006 He was suspected for CML and investigated for same. He visited Tata Memorial hospital and was found to have Philadelphia chromosome positive. He was started on Imatinib. As he had his renal derangement also , he was often had to move between KEM hospital Mumbai and Tata Memorial Hospital.
The patient was on Imatinib till August 2007, along with dialysis, thrice weekly. In July/August 2007 he started developing resistance to Imatinib.
The resistance to Imatinib was proven by mutation studies. E 4536 mutation.
He was offered Dastanib for 2 months. The support for Dastanib could not be extended because of financial constraints. He was a beneficiary of Railways.
The nephrologist state that it is Chronic Renal disease stage V at present.
He tested positive for anti-Hbsag antibodies in June 2006.
He was on Hydroxyurea with stable disease and was undergoing dialysis when I had written this summary in June 2008.
I happened to meet his father while on a journey. Decided to facilitate the best I could. They were reluctant to go to Tata Hospital again.
I discussed the case with Dr.Lalit from AIIMS at a conference in 2008. He suggested that both Bone Marrow Transplant and Kidney transplant can be done for this boy at a single setting. Encouraged by this I gave some hope to the boy's father. He was willing to do anything and go any where to get his son cured.
They also got HLA test done and the report was sent to HLA scientist at AIIMS. I copy the reply below
"Prof Lalit Kr from Medical Oncology requested me to reply to you regarding HLA reports of your patient Mr X.
As per the HLA reports the sister seems to be a match and can be considered as a donor for BMT and the mother for the renal transplant.
In this case it seems the testing has been done by serology and we have only one HLA-A antigen identified for both patient and his sister ( HLA-A2, A-). It is possible that the second antigen is also HLA-A2 ( i.e. A2 inherited from both mother and father ) but unless the father's report is available and that shows presence of HLA-A2 we would not be sure that the children have inherited HLA-A2 from both parents. Its also possible that the second HLA-A antigen is something else and not A2.
Alternatively, if the test is done by molecular technique, and that too shows the same results as serolgy test, we would be sure.
For all transplants patients at AIIMS, initial screening of family is done by serology to pick a potential donor. However, as a policy we normally confirm the matching status by a molecular test before the patient undergoes BMT.
I do hope the above information is helpful.
Once the molecular tests are done, I will be happy to review the reports again if you feel the need."
We sent the blood to Delhi and also the boy traveled to AIIMS.
The next reply was,
"We have tested the patient and his donor for HLA class I genes and we shall proceed with the Class II gene testing tomorrow.
I just need to find out if the patients father has been tested or not. As was mentioned in previous reports, we also notice only one HLA-A allele in both patient and donor. The purpose of testing again was to check what are the HLA genes inherited from father. We are presuming on the basis of previous and current reports that itis HLA-A2 but having fathers' reports will be very helpful.
As soon as we have completed the tests we shall send the reports and receipts. In the meantime if the father is not tested, can we suggest that he be tested and report sent to us."
The next reply
"X's test was done and reports were complete by last week of may. Yesterday we have received the reports of X's father and we are now very sure of the HLA tests done for X and his sister . They are a perfect match and the BMT can be planned for the patient.
Ponatinib is a second generation tyrosine kinase inhibitor while as rest all are first generation. Omacetaxine is an inject-able agent against protein synthesis. Ponatinib and Omacetaxine are also effective against the tough acquired mutation called T315I.
As I read about the progress being made I am reminded of a case which i had encountered few years back.
A 15 year old boy in Jan 2005 presented with weakness, etc.
Feb 2005 Hb-12.5 gm%, WBC 52,000. ( No comment on blast cells etc.)
Serum Creatinine 2.1. He was evaluated by physicians and nephrologist.
He was diagnosed to have Ig A Nephropathy with Chronic renal insufficiency.
Biopsy report reads -Mesangioproliferative glomerulonephritis.
For one year he was managed as Nephrotic patient only.
March 2006 He was suspected for CML and investigated for same. He visited Tata Memorial hospital and was found to have Philadelphia chromosome positive. He was started on Imatinib. As he had his renal derangement also , he was often had to move between KEM hospital Mumbai and Tata Memorial Hospital.
The patient was on Imatinib till August 2007, along with dialysis, thrice weekly. In July/August 2007 he started developing resistance to Imatinib.
The resistance to Imatinib was proven by mutation studies. E 4536 mutation.
He was offered Dastanib for 2 months. The support for Dastanib could not be extended because of financial constraints. He was a beneficiary of Railways.
The nephrologist state that it is Chronic Renal disease stage V at present.
He tested positive for anti-Hbsag antibodies in June 2006.
He was on Hydroxyurea with stable disease and was undergoing dialysis when I had written this summary in June 2008.
I happened to meet his father while on a journey. Decided to facilitate the best I could. They were reluctant to go to Tata Hospital again.
I discussed the case with Dr.Lalit from AIIMS at a conference in 2008. He suggested that both Bone Marrow Transplant and Kidney transplant can be done for this boy at a single setting. Encouraged by this I gave some hope to the boy's father. He was willing to do anything and go any where to get his son cured.
They also got HLA test done and the report was sent to HLA scientist at AIIMS. I copy the reply below
"Prof Lalit Kr from Medical Oncology requested me to reply to you regarding HLA reports of your patient Mr X.
As per the HLA reports the sister seems to be a match and can be considered as a donor for BMT and the mother for the renal transplant.
In this case it seems the testing has been done by serology and we have only one HLA-A antigen identified for both patient and his sister ( HLA-A2, A-). It is possible that the second antigen is also HLA-A2 ( i.e. A2 inherited from both mother and father ) but unless the father's report is available and that shows presence of HLA-A2 we would not be sure that the children have inherited HLA-A2 from both parents. Its also possible that the second HLA-A antigen is something else and not A2.
Alternatively, if the test is done by molecular technique, and that too shows the same results as serolgy test, we would be sure.
For all transplants patients at AIIMS, initial screening of family is done by serology to pick a potential donor. However, as a policy we normally confirm the matching status by a molecular test before the patient undergoes BMT.
I do hope the above information is helpful.
Once the molecular tests are done, I will be happy to review the reports again if you feel the need."
We sent the blood to Delhi and also the boy traveled to AIIMS.
The next reply was,
"We have tested the patient and his donor for HLA class I genes and we shall proceed with the Class II gene testing tomorrow.
I just need to find out if the patients father has been tested or not. As was mentioned in previous reports, we also notice only one HLA-A allele in both patient and donor. The purpose of testing again was to check what are the HLA genes inherited from father. We are presuming on the basis of previous and current reports that itis HLA-A2 but having fathers' reports will be very helpful.
As soon as we have completed the tests we shall send the reports and receipts. In the meantime if the father is not tested, can we suggest that he be tested and report sent to us."
The next reply
"X's test was done and reports were complete by last week of may. Yesterday we have received the reports of X's father and we are now very sure of the HLA tests done for X and his sister . They are a perfect match and the BMT can be planned for the patient.
Unfortunately I do not know the end of the story. The boy did not undergo the transplant at AIIMS for various reasons. He was taking his treatment at St.Johns Hopsital, Bangalore when I knew last.
Very eager to know how he is doing now.
Lessons for me:
1. Should have followed up with the father. I felt guilty of not being able to do much for him and stopped communication. The father also had got tired of me !
2. The need for well planned research in India. Information about the same made available to all doctors.
3. Unique cases need extra perseverance and innovative action plan. In routine practice when clinicians are overburdened they triage their time and effort towards curable and simple cases. Need for special units to take care of complex cases.
4.Making care affordable and available.
Learning never ends........
Tuesday, April 09, 2013
Vaccines In Cancer
We all are aiming and waiting for the day when one can get vaccinated against cancer!
Vaccines can be of two types prophylactic and therapeutic. Prophylactic ones have been developed for few cancers.
Hepatitis B vaccine is predominantly encouraged to prevent oneself from Hepatocellular cancer. This has helped in keeping the rate of liver cancer in check. Liver cancer is a leading problem in China, Taiwan, India etc. In US, hepatitis C infection is expected to create a huge burden of liver cancer in baby boomers. Efforts are on to bring better therapy for hepatitis c.
Another vaccine which has the potential to make an impact is HPV vaccine. HPV vaccines from GSK and Merck are expected to decrease the incidence of cervical carcinoma. There are many types of HPV virus and these vaccines take care of HPV 16, 18. The immunity against these is expected to help fight against other HPV's also. Vaccinated or not, it is highly recommended to get oneself screened for cervical carcinoma.
Provenge, sipuleucel-T, for prostate cancer is a successful therapeutic vaccine for prostate cancer used in metastatic setting.
There are plenty of therapeutic vaccines in clinical trials for lung cancer, head and neck cancer, brain cancer, melanoma.
Next few years are interesting but none of the vaccines are any near to cure.
Reference: http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines
Vaccines can be of two types prophylactic and therapeutic. Prophylactic ones have been developed for few cancers.
Hepatitis B vaccine is predominantly encouraged to prevent oneself from Hepatocellular cancer. This has helped in keeping the rate of liver cancer in check. Liver cancer is a leading problem in China, Taiwan, India etc. In US, hepatitis C infection is expected to create a huge burden of liver cancer in baby boomers. Efforts are on to bring better therapy for hepatitis c.
Another vaccine which has the potential to make an impact is HPV vaccine. HPV vaccines from GSK and Merck are expected to decrease the incidence of cervical carcinoma. There are many types of HPV virus and these vaccines take care of HPV 16, 18. The immunity against these is expected to help fight against other HPV's also. Vaccinated or not, it is highly recommended to get oneself screened for cervical carcinoma.
Provenge, sipuleucel-T, for prostate cancer is a successful therapeutic vaccine for prostate cancer used in metastatic setting.
There are plenty of therapeutic vaccines in clinical trials for lung cancer, head and neck cancer, brain cancer, melanoma.
Next few years are interesting but none of the vaccines are any near to cure.
Reference: http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines
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