You always know that the day will come that your life may be coming to end. For some it comes early, for some in mid life and hopefully for the rest of us when we are old and gray.
During the road of life we take risks, we do dumb things and we make choices because we think we are fearless, a superman of sorts and you only die when you are old. We spend much of our lives in the early years chasing the girls, then getting married and having a family, then years cultivating our careers so we can have the lifestyle that we have always dreamed of and along the way we forget about ourselves and the choices we made not to mention the damage these choices can do to you later in life. They say when you have a life changing situation the best thing is to write it down because you may want to share it with others so here we go.
Over and over we hear and read about all the bad things that can happen to us from alcohol, drugs and smoking. Do we listen? We all know the answer to that for we continue to do bad things to our body. I am just as guilty because I didn
I am a firm believer in planning whatever I want to achieve in my life. Planning (and taking all the actions required to realise the plan) was invaluable in coping with my six lifetime cancer diagnoses.
First diagnosed in 1979, in 2004 I faced my most challenging cancer encounter. For the second time in my life the lymphoma had relapsed to stage 4 (there is no stage 5). Six months of chemotherapy preceded the removal of my spleen, high-dose chemotherapy and a stem-cell transplant.
The combined effects of advanced disease and treatments left me weaker and less mobile than ever before. My willpower, determination and exuberance for life, which had always been my strongest suits, were waning.
My plan for coping included employing a range of psychosocial support measures that had helped me in the past. I drew from my humour library, regularly watching my favourite comedies to lift my spirits. I played music to help me express and manage my emotions. I wrote about what I was experiencing each day to help me examine and vent my feelings.
What helped most though was carrying out a review of my life; looking at whether it was everything I wanted it to be (the cancer notwithstanding). When at your lowest ebb, you need everything possible in your present and future to encourage you to hold on. Reflecting on all areas of my life I realised I needed to change my vocation.
I had never enjoyed some aspects of being a corporate manager. By nature I loved to create and positively influence those around me, while the corporate world is driven by competitiveness and immersed in politics, where values are often surrendered for self-interest. There was a fundamental mismatch between who I was and what I did for a living and I felt remedying this would help my recovery aspirations.
I wrote a compelling vision statement to focus me on a new career and lifestyle: To show people how to live happier and more fulfilling lives. For me this meant doing a number of things. I had long intended to write a book on how to take action to help cope with a cancer battle. I set this project as a high priority.
One thing I had really enjoyed about my corporate job was helping my staff develop and grow as people. I did some research and resolved that I would be able to focus on this for a living as a life and career coach.
I also wanted to give something back in recognition of the support I had received in coping with cancer throughout my life. Like so many people I had benefited greatly from the services of my local Cancer Society, but many others had given freely and generously to help me cope too. I decided that after I had recovered I would find forums to deliver talks about the coping strategies I would subsequently write about in my book Life, Happiness & Cancer.
The motivation and excitement generated by my life-after-cancer planning helped me re-gain my zest for life and emotional strength. I began to cope better with the treatments and my recovery progressed well. By Christmas 2004 I was back at home in full remission. My energies returned steadily along with my hair, as I put my plan into action full of enthusiasm for life.
That was over two years ago. I found happiness and fulfilment in my new activities. I wrote and published my book, which became and remains a bestseller in New Zealand. I trained to become a life and career coach and established my own business. I was even discovered (as they say) while promoting my book on television, and became the resident life coach on a morning TV show. And as Christmas 2006 arrived I had delivered my Life, Happiness & Cancer presentation to over 1,500 people at 31 forums.
But my ultimate joy came in November 2006 when I learned my wife Gillian was pregnant with our first child. This too, we planned!
The great English poet WH Auden defined cancer as a foiled creative fire. For me, reigniting my own fire by planning a new lifestyle and career helped me cope with and eventually overcome cancer, and to establish an even better life than before.
Phil Kerslake lives in New Zealand, is a six-time survivor of different lymphomas across four decades and the author of the 2006 book Life, Happiness & Cancer: Survive with Action and Attitude! For more information about Phil, his book and presentations to cancer support conferences visit his website www.lifepaths.co.nz.
When it comes to fighting cancer, many people seem to want to go it alone. For some reason we view the cancer struggle as a private affair and often hold at arms length people who might otherwise have helped us immensely. I know because I was certainly one of those people in 1979 when I was first diagnosed with a lymphoma as a teenager. In 1987 when I was admitted to Wellington hospital with widespread, advanced disease I was still of the mind that the business of beating my cancer was mine alone, making it clear to even my closest friends that they were to leave me alone until I surfaced again, with full health restored.
You can therefore imagine my response when invited to attend cancer support groups back then. I avoided them like the plague. I was clearly a loner when it came to facing my health problems but on top of that I had a terribly negative image of cancer support groups. I had this preconception of mutual moaning forums. I also very uncharitably believed people who joined a group were not strong enough to face their battles alone. I saw myself as stronger than that.
I was intrigued then in the early 1990s when, with an early notion of writing a book on boosting quality of life and maybe even the odds of beating cancer I came across screeds of material lauding cancer support groups for their therapeutic benefits. My reading suggested a safe, positive and unpretentious environment where participants could express their feelings but also simply share the nuances and peculiarities of the cancer experience with people in the same predicament as they.
First and foremost, the literature said, a support group enabled you to express yourself in a safe and truly understanding forum. An important benefit of a group was said to be that it allowed the cancer patient to regain some sense of control in their lives after a period since their diagnosis where they had quite possibly felt out of control in every sense. Amongst other people facing similar challenges life crises are put into better perspective. I knew as a cancer survivor that when diagnosed with the disease you can and often do feel like the only one afflicted.
In 1994 I received another recurrence scare. This time my recurrence was localized and some weeks of radiotherapy cleared the disease. However for me that didnt lessen the usual associated fears, reflections and element of post-treatment depression. I decided to change my coping pattern and took steps to link up with a support group for a period of time. What I experienced reflected all the good things Id read about cancer support groups and more. I found the group to be a strong set of individuals. While we all had our fears about the present and the future, there was a dignity and resilience in each person that I admired greatly.
People didnt complain or whine as I had imagined those years before. Each person brought their own coping approaches to the table and I found that I learned from them. I became more open, more giving and more sharing. I actually believe that I became a better person for the experience. When I had my latest recurrence from late 2003 through all of 2004, I found myself with an entirely different coping style which served me well. This time I was open to all my friends and family in the experience and I know that the reciprocated love, caring and openness made a difference for me. It may have been the difference in my recovery.
Even the most individualistic of us cannot be Islands unto ourselves. Even the strongest and most private of us needs to open ourselves up to others. Being able to share our experiences during a cancer battle helps us achieve a more settled state of mind which underpins our recovery aspirations. Now, as a 47 year old man with 28 years experience with cancer my first advice to the newly diagnosed is to find a cancer support group and allow the collective dignity, strength and humanity found there to steady and ground them for the difficult experience ahead.
Phil Kerslake is a New Zealand six-time cancer survivor, speaker to cancer support forums worldwide and author of the 2006 book: Life, Happiness & Cancer: Survive with Action and Attitude! For more about Phil, his book and speaking services visit his website www.lifepaths.co.nz.
Functional profiling with cell culture assays for targeted drug therapy
Recent findings presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in Orlando, Florida concluded that Functional Profiling (whole cell profiling) with cell culture assays is relevant for the study of both "conventional" and "targeted" antineoplastic drug agents.
Cell Culture Assays with "cell-death" endpoints can show disease-specific drug activity, are useful clinical and research tools for "conventional" and "targeted" drugs, and provide unique information complementary to that provided by "molecular" tests. There have been more than 25 peer-reviewed publicatons showing significant correlations between cell-death assay results and patient response and survival.
The Whole Cell Profiling technique is a cell-death endpoint assay in which drug effect upon cancer cells is visualized directly. Photomicrographs of actual tumor cells sometime show that the exact same identical individual culture well, shows some clusters have taken up vast amounts of a drug, while right next door, clusters of the same size, same appearance, same everything haven't taken up any of the drug.
So it doesn't matter if there is a "target" molecule (protein or receptor) in the cell that the targeted drug is going after, if the drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, drug resistance is multifactorial. The advantage of the Whole Cell Profiling technique is that it can show this in the "population" of cells.
The Whole Cell Profiling technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results which are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.
This could help solve the problem of knowing which patients can tolerate costly, new treatments and their harmful side-effects. These "smart" drugs are a really exciting element of cancer medicine, but do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.
Functional profiling (FP) with cell culture assays for targeted drug therapy.
Sub-category: Translational research
Category: Colon and Rectum
Meeting: 2007 Gastrointestinal Cancers Symposium
Abstract No: 440
Author(s): L. M. Weisenthal
Abstract: Introduction: We studied the relevance of FP for standard and targeted drugs.
Methods: Drugs were tested against fresh human tumor microclusters, with 96 hr drug exposures and multiple FP endpoints (MTT, DISC, resazurin, and/or ATP).
Results: In 65 previously chemonaive stage 4 colon cancer patients, those with FP assays showing 5FU results in the most resistant tertile had inferior overall survival, compared to pts without 5FU resistance (303 days vs. 686 days, H.R. 2.1, 95% C.I. 1.2 - 5.0, P2=0.011). In subset analysis restricted only to 53 pts who subsequently died (eliminating potential surgical cures), the respective results were 292 vs 493 days, HR 1.5 - 6.9, P2=0.0021. We applied FP to test targeted agents, including gefitinib, erlotinib, sunitinib, sorafenib, and bevacizumab. Gefitinib was tested against > 700 fresh tumor specimens; we reported striking correlations between gefitinib activity and overall pt survival in non-small lung cancer (2006 ASCO Annu Mtg, Abst 17117). Gefitinib and erlotinib are moderately cross resistant (R2=0.48, n paired comparisons=190). Gefitinib/sunitinib (R2=0.20, n=46) and erlotinib/sunitinib (R2=0.12, n=44) are largely non-cross resistant. We also developed a new microvascular viability assay (MVVA) to test microvascular cells present in tumor clusters. In the MVVA, bevacizumab was tested in 81 fresh tumor specimens (including 15 GI). Bevacizumab was nontoxic to the tumor cells, but often strikingly toxic to microvascular cells present within the same tumor clusters. Grading on a 0-4 scale, there was absent (Gr 0) effect in 23 specimens, weak (Gr 1-2) effect in 28, and a strong (Gr 3-4) effect in 26. In contrast to bevacizumab, neither sunitinib (n=87) nor sorafenib (n=20) showed selective effects against microvascular cells compared to tumor cells.
Conclusions: We cannot rule out a cytostatic effect of sunitinib or sorafenib on tumor microvascular cells. However, our results imply that the antitumor effects of bevacizumab are predominately mediated through antimicrovascular effects, while effects of sunitinib and sorafenib may be mediated largely through tumor cell apoptosis. We conclude that FP is relevant for the study of both traditional and targeted antineoplastic agents.
The high recurrence after surical resection of HCC is a major therapeutic challenge. This adjuvant treatment into the hepatic artery has been proposed by Lau WY, Leung TW, et al in previous studies. In 2005, treatment was in phase III clinical trials in Singapore.
As we enter the era of "personalized" medicine, it is time to take a fresh look at how we evaluate treatments for cancer patients. More emphasis should be put on matching treatment to the patient. Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.
Findings presented at the 41st Annual Meeting of the European Society for Clinical Investigation in Uppsala, Sweden, April 18, 2007, concluded that "functional profiling" with cell culture assays is relevant for the study of both "conventional" and "targeted" anti-neoplastic drug agents (anti-tumor and anti-angiogenic activity of Iressa, Tarceva, Sutent, Nexavar, and Avastin in primary cultures of "fresh" human tumors).
Cell Culture Assays with "cell-death" endpoints can show disease-specific drug activity, are useful clinical and research tools for "conventional" and "targeted" drugs, and provide unique information complementary to that provided by "molecular" tests. There have been more than 25 peer-reviewed publications showing significant correlations between cell-death assay results and patient response and survival.
Many patients are treated not only with a "targeted" therapy drug like Tarceva, Avastin, or Iressa, but with a combination of chemotherapy drugs. Therefore, existing DNA or RNA sequences or expression of individual proteins often examine only one compenent of a much larger, interactive process. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability.
There is a tactic of using biopsied cells to predict which cancer treatments will work best for the patient, by taking pieces of live "fresh" tumor tissue, applying different chemotherapy treatments to it, and examining the results to see which drug or combination of drugs does the best job killing the tumor cells. A cell culture assay test with "functional profiling," using a cell-death endpoint, can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).
"Funtional profiling" measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, "functional profiling" is measuring them through the surrogate of measuring if the cell is alive or dead.
For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR-inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.
As an example of this testing, researchers have tested how well a pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast, and colorectal cancers. The pre-test can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer.
The "funtional profiling" technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results that are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.
This could help solve the problem of knowing which patients can tolerate costly new treatments and their harmful side effects. These "smart" drugs are a really exciting element of cancer medicine, but do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.
According to a study by Dr. Holly Gallion, published in the International Journal of Gynecological Cancer (IJGC) researchers using the Chemo FX Assay by Precision Therapeutics, identified which chemo agent would be most lethal to an individual patient's cancer. In the study of 256 women with recurrent ovarian cancer, the time women went before a worsening of their disease was two to three times longer if they were treated with an assay-sensitive drug compared to an assay-resistant drug. The bottom line is the assay is able to predict the patient's response to treatment. The Chemo FX is a (cell-death) assay test. Their study adds to the already large body of evidence of the accuracy of cell culture assays in ovarian cancer.
The assay determines which agents are most potent against a specific tumor and what concentration works best. No more hit or miss in the patient. Armed with that information, the treating physician and patient can proceed with a chemo regimen likely to work right out of the gate and subjecting the patient to less toxicity. If the assay finds that the tumor responds to none of the currently avialable treatments, a patient could then be referred to a clinical trial before a history of less useful treatments rules her out as a clinical trial candidate.
In light of the precious little in the way of guidance from clinical trials with respect to best empiric treatment, oncologists give treatments knowing full well that only a certain percentage of patients will receive a benefit from any given medicine. They subject patients to one combination chemotherapy after another, just going from one journal paper to another journal paper. They need information about the characteristics that predict which patients are more likely to respond well. The empirical approach, which is based on medical journal articles, epidemiology and economics, doesn't tell doctors how to personalize their care to individual patients. Physicians' decisions need to be based on personal experience, clinical insights, and medical training.
Cell culture assay measures the net effect of all processes within the cancer, acting with and against each other in real time, and it tests living cells actually exposed to drugs and drug combinations of interest. Tens of thousands of individual patient specimens are currently being submitted for testing by more than 1,000 clinical oncologists, surgeons and pathologists annually in the U.S. It is certainly each practitioner's prerogative to order these tests. It seems probable that a self-educated oncologist, genuinely on the cutting-edge would tend to be aggressive in actual treatment beyond mere rhetoric, and make use of running tests on a "fresh" tumor specimen before selecting a chemotherapy option.
Gallion, H. H., W. A. Christopherson, et al. (Jan/Feb 2006). "Relationship between ex vivo chemosensitivity assay and progression free interval in ovarian cancer." International Journal of Gynecological Cancer
PubMed lists a paper that reports an increase from 35% to 65% response rate for recurrent ovarian cancer patients when cell culture assay tests were used to select the chemotherapy drugs. The P values (P=.005, etc.) given are measures of the statistical significance of the findings. The smaller the number, the higher the statistical significance. "P" refers to the probability that the finding is due to random chance. So, high P values are bad. P values of 5% or less are deemed to be statistically significant. All of the P values reported in this study indicate that the results are, indeeed, statistically significant.
(Am J Obstet Gynecol. 2003 Nov;189(5):1301-7)
Data from the Columbia University Department of Urology demonstrates that Zyflamend
The story of how Veterans exposed to ionizing radiation are now comming down with cancer.
Important research in the followup of well differentiated thyroid carcinoma.
Pub Med Citation: