john
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Posts posted by john
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Happy for both of you. Not sure who it was, but someone on here posted about going to cancer center of america and thought it was the better than any other place they had been.
Take care
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Some people here have suggested body builder drinks, like weight gain 1000. They have around 1000 calories per drink.
My mom drank it for a while, not sure of the exact brand but it didn't have the bad aftertaste like some of the protien drinks do.
These drinks dont have much sugar and are fortified with vitamins and minerals
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Thanks for the condolences
Force the hmo to get you to a cancer specialist - ASAP
Good luck. At least it is still relatively small, but it is almost criminal waiting so long. It will help if you quit smoking.
quiting smoking will let you tolerate the different treatments better.
Best of luck
God Bless
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Like Don I was leary of Dr Burzynski. However, he has made it to a clinical trial, so there probably is some evidence that his therapy may work.
here is the info, I just saw this recently
http://www.clinicaltrials.gov/ct/show/N ... 2?order=33
There are restrictions. You probably have to wait at least a month if not more after going off the Tarceva
Good luck and take care
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get a second opinion. But ask the Dr what the doubling time is?
1-6 months is bad. non-calcified is bad
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If is growing I would be concerned. Like other people said - how big was it initially and how big is it now?
Is it calcified or non-calcified - I believe non-calcified is more likely malignant, but you can search on calcification and probably find an anwer
A PET could help, if it is big enough. I'ld get another opinion from a cancer specialist
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I did not know this before. If there are tumors on the same side of the lung in a different lobes in is considered stage IV.
http://willroberts.com/lungcancer/staging.html
I am not a doctor but that *seems* better than distant mets
Take care
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Sorry about your mom. remember there are a number of people here who are long term survivors. So it is not an automatic death sentence
Did it spread to both sides of the lungs? Then it would be stage 4.
You should find out about the histology (cell) type.
They will tell you adenocarcinoma, squamous, etc.
Since it did not spread out of the lungs it could be BAC (a subtype of adeno). This has a tendency to be stay in the lungs.
Find out how many tumors, size, and grade (differentiated/undifferentiated). Maybe RFA (radio frequecy ablation) is a possibility or even a chemo embolism?
Ask about clinical trials, if she is indeed stage 4, before treatment starts. If you start treatment TOO soon, if will affect her choices later. But definitely get answers FAST and push to get treatment soon.
Take care
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Did they test for VEGF? If the your dad's tumor does not "express" this, then I am not sure if it is the best.
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Are they treating it as pancreatic or Gastrointestinal cancer?
http://www.mskcc.org/mskcc/html/5491.cfm
http://www-pp.hogia.net/carpa/neuroendo%20en.html
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
It is pretty confusing, because some neuroendocrine tumors grow slow and others are more aggressive. Find out from the doctor if the tumor is undifferentiated, poorly differentiated or differentiated.
How did they determine it was neuroendocrine? I imagine they did a
somatostatin receptor scintigraphy (Octreoscan) or other scan for for somatostatin receptors
Neuroendocrine tumors are supposed to be rare, but it seems like more people here have them. SCLC is a neuroendocrine tumor
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A PET scan is used to determine where the cancer is. The person is injected with a sugar solution that contains radioactive material. Cancer shows higher "uptake" of the sugar so it shows up as "light" spots on a scan.
The first thing that happens when a Doctor suspects cancer is a biopsy (if possible) and then staging. Staging determines how far the cancer is spread. PET is a non-invasive procedure. A medianoscopy can also be used to check lymph nodes. There are also other diagnostic tools
Unfortunately, no test is 100%. Based on the tests they will stage the cancer. If the cancer has spread too far then surgery will not likely help, since it is "systemic" versus local to the lungs.
Stage I and II are typically treated with surgery.
Stage III is borderline. Chemo-radiation before surgery is the best *I believe*
Stage IV is only treated with chemo/radiation
That is for Non-small cell
Small cell is divided into limited and extensive. Small cell responds well to chemo but it often (but not always) reoccurs.
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oopppss.. I meant somatostatin receptors
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I was told by my Aunt who is a pediatrician. She talked to a bunch of oncologists. She was told Indium-111 may be a treatment for cancer with sandostatin receptors
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CPT-11
in SCLC GROUP
Yes. I agree. It seems like the evidence is that Irinotecan/Cisplatin works the best. I think it is because Japan has been using this successfully and maybe the american doctors don't trust the research outside of this country. Just a thought.
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Almost three years old, but it seems not widely available
Sputum Testing for Precancerous Lung Cells Progresses Toward the Clinic
Effective sputum testing to detect pre-cancerous cells in the airways now appears likely to become an important diagnostic tool. Although obstacles to its clinical acceptance remain, technological advances and discoveries in genetics and biomarkers have enabled researchers to detect cell changes indicative of lung cancer 1 to 2 years in advance of clinical disease.
Moreover, combining sputum testing with spiral computed tomography (CT) scanning should give a two-step diagnostic battery that could save millions of lives among the 80 million US smokers and former smokers who are at high risk for developing lung cancer. "I see them as two complementary approaches for early lung cancer detection," said Melvyn S. Tockman, MD, PhD, professor of medicine and director of molecular screening at H. Lee Moffitt Cancer Center and Research Institute. "This is predicated on us changing the paradigm from detection of cancer to detection of carcinogenesis."
By definition, carcinogenesis is not simply the disease state but a process that involves both neoplastic transformation and malignant growth. "So we are looking for evidence of change toward the process of carcinogenesis rather than for a single disease entity," he said. "There is a clonal phase for preinvasive lesions. Even before these cancer cells begin to invade the basement membrane, they are detectable as preinvasive lesions. We can sample their transformation and progression because many of these cells will exfoliate before they actually begin to invade.
The concept is that these cells, all through the airway, have been subject to an insult for 20 to 30 years, and that the genetic change that occurs in these cells occurs throughout the airway. Many of these genetic changes actually preceded the change in cell structures. So we can see genetic changes that actually precede morphology.
Dr. Tockman and his colleagues have investigated a protein called hnRNP, and found that it goes through a controlled, or normal expression, and an uncontrolled expression that is associated with tumors. Both normal bronchial epithelial cells taken from lung cancer patients and grown in the laboratory and cancer lines strongly express hnRNP. Normal cells, however, significantly down-regulate hnRNP expression when they reach confluence. Cancer cells keep growing. Also, in normal cells, the hnRNP forms perinuclear granules; in cancer cells, the protein is diffused throughout the cell.
"So, just as in the culture dishes, we see signs that the tumor is showing uncontrolled growth throughout the cytoplasm," Dr. Tockman said. "Interestingly, the hnRNP protein can be seen in exfoliated cells that can be coughed up in the sputum. And even in cells that are not frankly malignant, the pattern of protein expression in the cytoplasm is the same as we see in the tumor."
hnRNP Staining Technique
Moreover, with the aid of a computer program, the presence of hnRNP can be measured in the cell cytoplasm and its morphology determined using a staining technique. In several clinical trials, researchers have detected evidence of cell transformation up to 2 years in advance of the disease. In one study, the Lung Cancer Early Detection Working Group found that 660 patients whose tumors were resected were at risk of developing a second primary cancer. Thirteen of the patients did. hnRNP staining was positive in 77% of them, and negative in 82% of the patients who did not develop a second tumor.
In a study of 6,000 Chinese miners who smoked and were exposed to radon and arsenic while working underground, 56 developed primary lung cancer. The staining technique was positive in 82% of those 56 and negative in 65% of others who did not develop a tumor. In a Liverpool, England, study, 57 individuals went on to develop lung cancer and 95% of them had a positive staining, while 84% of those who did not get the disease had a negative screening.
"We are very encouraged by the sensitivity and specificity of this technique," Dr. Tockman said. "Recently, we conducted a blinded reappraisal of these specimens and found that the result held up, with an 80% and 86% sensitivity and specificity, respectively."
Adenocarcinomas Most Commonly Detected
Both spiral CT scanning and hnRNP in sputum detect cells that are complementary in terms of both stage and cell type, Dr. Tockman said. He noted that the paper published by Claudia Henschke, MD, PhD, and her colleagues in Lancet in 1999 showed that the majority of cancers detected by spiral CT scanning were adenocarcinomas, the cell type that is associated with peripheral lesions. Eleven percent were adenosquamous, 4% were squamous, and no large- or small-cell cancers were detected. In contrast, in the Lung Cancer Early Detection Working Group study, hnRNP detected early signs of the four major cells types seen in the general population. This suggests, he said, "that many of the earlier lesions in the central airways may be better detected by mechanisms using molecular markers and sputum, than perhaps by radiography."
Sputum collection today is marked by poor specimen preservation and preparation, which results in many unsatisfactory sputum specimens, Dr. Tockman noted. Nonetheless, "industry is very aware of the problem and is developing solutions for sputum collection."
In addition to hnRNP, several other biomarkers appear to offer great potential for screening cellular RNA for signs of early cancer. And researchers are examining the usefulness of several DNA markers, including one technique that detects gene promoter hypermethylation as a sign that carcinogenesis is active in the lungs.
At the Moffitt Cancer Center, Dr. Tockman and his colleagues are currently testing the hypothesis that combining hnRNP sputum sampling and spiral CT scanning will increase the percentage of stage I lung cancers detected by at least threefold. The subject population consists of individuals at least 45 years old with a smoking history of 30 pack-years. According to Florida cancer statistics, only 20% of patients diagnosed with lung cancer have resectable (stage I) disease. The Moffitt team expects that 60% of the lung cancers they find will be stage I tumors.
"The development of computers and diagnostic platforms is making cost-effective mass screenings for lung cancer by helical CT and sputum molecular airway markers possible," Dr. Tockman said. "Compared to helical CT, molecular airway markers detect lung cancers at a complementary stage (clonal and preinvasive vs invasive), complementary location (central vs peripheral), and complementary cell types. The widespread enthusiasm for trials of helical CT screening will allow the additional assessment of several roles for sputum molecular markers at little cost."
However, he warned, physicians and the public need to temper their enthusiasm for early lung cancer testing for now, he added. "The large numbers of persons at risk for lung cancer require careful assessment of these molecular and helical CT screening techniques and management algorithms before their widespread adoption. We have got to do the science before we bring it to the public."
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Gemcitabine/Carboplatin Improves Survival in Lung Cancer Patients
LINKOPING, Sweden—Swedish researchers found that gemcitabine (Gemzar) plus carboplatin (Paraplatin) improved response rates and survival in patients with advanced non–small-cell lung cancer during a phase III trial, according to a presentation by C. Sederholm, MD, on behalf of the Swedish Lung Cancer Study Group. Dr. Sederholm is with the department of pulmonary medicine at University Hospital, Linkoping (ASCO abstract 1162).
"Combination gemcitabine plus carboplatin increased survival without complicating toxicities or detriment to quality of life compared with gemcitabine alone," Dr. Sederholm said.
Researchers enrolled 334 patients at 17 centers from October 1998 through January 2001. Eligibility criteria included histologically/cytologically confirmed stage IIIB or IV disease and performance status of 0 to 2. There was no upper age limit. Patients with known central nervous system metastatic disease were excluded.
The primary study endpoint was survival. Secondary endpoints were quality of life, safety, time to progression, and response rate.
Treatment Protocol
Patients were randomized into two treatment arms. In the first, 170 patients received an intravenous infusion of gemcitabine, 1,250 mg/m², on days 1 and 8, every 21 days. The 164 patients in the second arm were given the same regimen of gemcitabine plus carboplatin, AUC of 5, on day 1, every 21 days.
A maximum of six cycles were planned. Doses were adjusted downward according to hematologic toxicity. The median number of cycles given was five in the gemcitabine arm and six in the combination arm. The dose intensity was excellent in both treatment groups.
Patients were followed up every 2 months for a year and every 3 months after the first year until progressive disease or death. Second-line treatments were given. A crossover to second-line treatment with a platinum regimen was not allowed.
The treatment arms were well balanced, with no significant differences in prognostic factors. The median age was 67, with 40% of the patients being age 70 or older. The most common histology was adenocarcinoma (49% in each arm), followed by squamous cell carcinoma. More than a third of the patients had more than 5% weight loss at baseline, with a slight predominance in the gemcitabine arm (35% vs 29%). Eighty-five percent of the study population had a performance status of 0 to 1. Eight patients never received treatment for various reasons.
"The hematologic toxicity, grade 3 and 4, was as expected, definitely more pronounced in the combination arm, but there were no treatment-related deaths in either arm," Dr. Sederholm said. "Five percent of the patients in the combination arm experienced grade 3 hematologic toxicity, compared to less than 2% in the single-agent arm."
The most common toxicities were anemia, leukopenia, and thrombocytopenia. Chemotherapy-related infections were rare, with one in each arm. Thrombocytopenia, observed in a high proportion of patients in the combination arm, was short-lived, centering around day 15 and without clinical implications in the vast majority of patients. No major bleeding was reported. Nonhematologic toxicities were mild, with no significant differences between arms.
Combination Highly Beneficial
"The objective response rate in the 291 evaluable patients was highly significant in favor of the combination arm—30%, with two patients achieving a complete response, vs 12% in the gemcitabine arm," Dr. Sederholm said.
Time to progression in the intention-to-treat population was 4 to 6 months in the combination group, and the 1-year disease-free rate was 4% to 12%.
Second-line treatment was evenly distributed. Eight percent of the patients in the gemcitabine arm later crossed over to a platinum regimen against protocol.
Survival Data
Overall survival in the intention-to-treat analysis found 15% of patients still alive—8% in the gemcitabine arm and 27% in the gemcitabine-plus-carboplatin combination arm. The investigators found an overall survival benefit in favor of the gemcitabine/carboplatin combination.
"Overall survival was significantly superior in the combination group," Dr. Sederholm said. "The higher response rate, time to progression, and improved survival supports the use of these combinations even in elderly patients with good performance status."
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genistein may protect against cancer
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This study will evaluate the effect of a specially tailored vaccine to treat patients with non-small cell lung cancer. About 50 to 60 percent of patients with this type of cancer have a defective gene called p53, which produces a protein that protects their tumor from attack by the immune system. The vaccine is designed to stimulate the immune system to recognize the tumor cells and kill them.
The faulty p53 gene can cause various types of abnormalities that result in runaway growth of cancer cells. Each patient's vaccine will be custom matched to their specific p53 abnormality. After completing standard treatment--which may include chemotherapy, radiation and surgery--patients will be infused with the vaccine once a week for five weeks. Patients whose tumors respond to the treatment may receive additional vaccinations at two-month intervals for as long as they continue to benefit. In a previous small study, five out of five patients showed an immune response to p53 peptide vaccination.
Candidates for the study will be screened with a medical history, blood and urine tests and imaging studies (X rays and CT scans). A tumor sample will also be taken to see if it has a p53 abnormality suitable for this study. Study patients will undergo apheresis-a procedure to collect white blood cells needed to make their vaccine. In apheresis, blood is drawn through a needle in one arm, similar to donating blood. The blood goes through a machine that separates out some of the white cells, and the rest of the blood is returned, usually through a needle in the other arm. Patients will also have additional physical exams, blood tests, and imaging studies during the course of the study to evaluate the effects of treatment.
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Dave G,
Is this your Doctor? Joan Hoff Schiller
Peggy - Dr Schiller is the doctor running the vaccine trial in Madison. I believe this is Dave G's doctor.
In anycase, how is your sister. Is she still working, etc? If her performance status is good maybe she will qualify for the trial
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Here are a few links to trials. Some have very few exclusions.
http://www.clinicaltrials.gov/ct/gui/ac ... 2Cstage+IV
There is a gene called P53. It is a tumor supressor gene. Like the name suggests it causes cancer cells to die. If this gene becomes mutated, the resulting cancer is hard to treat, because the mutation causes the body to lose its ability to cause the cancer cells to die. There has been some evidence that soy may correct the mutation. You can get organic soy milk at the grocery store - the chocolate flavor actually tastes good.
Here are two trialsl for the P53 vaccine.
HERE IS ONE IN MADISON!!!
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There are currently 12 vaccine trials around the country for lung cancer.
Go to www.clinicaltrails.gov
search for vaccine,"lung cancer"
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The four (SCLC, Large cell neuroendocrine carcinoma (NCLEC), atypical and typical carcinoids) are all neuroendocrine tumors.
The main difference is the mitotic (cell division) rate of the tumors. SCLC, NCLEC have fast dividing cells. atypical and typical carcinoids are slower growing. Since chemo targets fast dividing cells that is why it does not work as well on carcinoids vs SCLC and NCLEC.
I am not sure why there was a name change (from carcinoma to carcinoid) - maybe just to differentiate the tumors.
Yes, Carleen's husband has atypical carcinoma. I refered her to you.
I am not sure why it is called atypical carcinoma vs atypical carcinoid.
I can't find the reference on PubMed but there was a small study that indicates NCLEC responds better to chemo than even SCLC for some reason.
My mom's tumor was resected. They thought she was Stage I. Nothing showed on the PET. The lymph nodes were tested and positive. So she was re-staged to IIIa.
After surgery, she received radiaiton and a vaccine. The doctors told her that after surgery chemo did not improve outcomes based on current research.
typical and atypical carcinoids have pretty good long term survival rates (up to 90%) for 10 years
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It seems like a lot of people get different diagnosis - sclc, then atypical carcinoid, etc. Here is an article about pathologists not being able to reach agreement on what type of cancer is found
Reproducibility of neuroendocrine lung tumor classification.
Travis WD, Gal AA, Colby TV, Klimstra DS, Falk R, Koss MN.
Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
For a tumor classification scheme to be useful, it must be reproducible and it must show clinical significance. Classification of neuroendocrine lung tumors is a difficult problem with little information about interobserver reproducibility. We sought to evaluate the classification of typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell carcinoma (SCC) tumors as proposed by W.D. Travis et al (Am J Surg Pathol 15:529, 1991). Forty neuroendocrine tumors were retrieved from the Armed Forces Institute of Pathology (AFIP) files and independently evaluated by five lung pathologists and classified as TC, AC, LCNEC, or SCC (pure SCC, mixed small cell/large cell, and combined SCC). A single hematoxylin and eosin-stained slide from each case was reviewed. Each participant was provided a set of tables summarizing the criteria for separation of the four major categories. Agreement was regarded as unanimous if all five pathologists agreed, a majority if four agreed, and a consensus if three or more pathologists agreed. The kappa statistic was calculated to measure the degree of agreement between two observers. A consensus diagnosis was achieved in all 40 cases (100%), a majority agreement in 31 of 40 (78%), and unanimous agreement in 22 of 40 (55%) of cases. Unanimous agreement occurred in seven of SCC (70%), seven of TC (58%), four of AC (50%), and four of LCNEC (40%). A majority diagnosis was achieved in 11 of 12 (92%) of TC, 9 of 10 (90%) of SCC, 6 of 8 (75%) of AC, and 5 of 10 (50%) of LCNEC. Most of the kappa values were 0.70 or greater, falling into the substantial agreement category. The most common disagreements fell between LCNEC and SCC, followed by TC and AC, and AC and LCNEC. The highest reproducibility occurred for SCC and TC, with disagreement in 8% and 10% of the diagnoses, respectively. For TC, 10% of the diagnoses rendered were AC. For AC, 15% of the diagnoses were rendered as TC, with 2.5% called LCNEC and 2.5% called SCC. For LCNEC, 18% and 4% of the diagnoses were called SCC and AC, respectively. For SCC, 4% of the diagnoses were called AC and 4% were called LCNEC. Thus, using the classification scheme tested, a consensus diagnosis can be achieved for virtually all neuroendocrine lung tumors with substantial agreement between experienced lung pathologists. Classification of NE tumors is most reproducible for classification of TC and SCC but less reproducible for AC and LCNEC. These results indicate a need for more careful definition and application of criteria for TC versus AC and SCC versus LCNEC.
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Libby,
Hopefully he will respond - and hopefully he can give your husband options
http://www.dfhcc.harvard.edu/member_det ... mberID=913
Philip J. Hahnfeldt, Ph.D.
Instructor
Department of Radiation Oncology, Harvard Medical School Printer-friendly version.
Contact Info
Dana-Farber Cancer Institute
44 Binney Street
Jimmy Fund Bldg, Rm 523
Boston, MA 02115
Phone: 617-632-3115
Fax: 617-632-4124
E-mail: philip_hahnfeldt@dfci.harvard.edu
Program Affiliation
Member in Angiogenesis, Invasion and Metastasis Program
DF/HCC Associations
No Associations are available for this member.
Research Abstract / Lab Focus
My current research focuses on the dynamical understanding of anti-angiogenic therapy for tumors from the standpoint of clinical implementation. In many respects, anti-angiogenic control is seen to recapitulate natural tissue-mass controls seen in human development. What we find specifically is that the classic 'Gompertz' tumor growth slowdown may be understood as an angiogenic process under negative feedback control from the tumor itself. I have published a quantitative description of how the tumor-vascular signaling interplay (involving angiogenic stimulators e.g. vascular endothelial growth factor, VEGF, balanced against natural angiogenic inhibitors e.g. endostatin) governs ultimate tumor growth [Cancer Res.59:4770-5, 1999].
In addition, because the target of anti-angiogenic therapy is not the tumor per se, but rather, its associated endothelium, I have undertaken to study the novel therapeutic issues and opportunities that arise. One category of these relates to the observation that endothelial targeting circumvents the classic drug resistance ultimately confronted under conventional chemotherapy. To study the implications of this observation for anti-angiogenic therapy, I am theoretically reexamining dosing protocols long held to be 'forbidden' by the standard "maximum tolerated dose" paradigm. What we stand to gain is a substantially expanded ability to tailor delivery protocols to further improve patient outcome.
Representative Citations
Tumor development under angiogenic signaling: a dynamical theory of tumor growth, treatment response, and postvascular dormancy.
Hahnfeldt P, Panigrahy D, Folkman J, Hlatky LR.
Cancer Res, Volume 59(19). October 1999:4770-5
PMID: 10519381
Polymer models for interphase chromosomes..
Hahnfeldt P, Hearst JE, Brenner DJ, Sachs RK, Hlatky LR.
PROCEEDINGS OF THE NATIONAL ACADEMY O..., Volume 90. Aug 1993:7854-8
PMID: 8356094
Maintence Program to keep SCLC in remission
in SCLC GROUP
Posted
Not sure if this could be something to look into ... BUT
Telomerase is an enzyme and found in 98% of sclc tumors. Telomerase allows a cell to become immortal, thus cancer results.
There is a trial at the NCI though it does not seem to be a telomerase inhibitor. it is a vaccine based on telomerase
http://www.clinicaltrials.gov/ct/show/N ... 40?order=1
Figure 4. Clinical trial design for telomerase inhibitors. (a) Aproposed phase III clinical trial design of telomerase inhibitors asmaintenance therapy in small cell lung cancer (SCLC) afterdebulking chemotherapy. hTERC expression is up-regulated in98% of cases of SCLC [2]. SCLC is extremely sensitive to first-line chemotherapy, but with a relatively short duration ofremission on completion of chemotherapy, with poor responsesto second-line chemotherapy regimens as a result of acquired orintrinsic drug resistance. SCLC is therefore an ideal model formaintenance studies with telomerase inhibitors. (
A proposedphase III clinical trial design of telomerase inhibitors incombination with cytotoxic chemotherapy in advanced breastcancer, for example, in comparison with chemotherapy alone,with progression-free survival and overall survival (if there is norecognized salvage therapy) as the main endpoints410W. N. Keith et al.Copyright # 2001 John Wiley & Sons, Ltd.J Pathol 2001; 195: 404?14.
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patient population in whom new agents are evaluated.Demonstration of efficacy in `minimal disease state'patient groups requires a phase III-type design withrelatively long follow-up, compared with conventionalphase II studies. In order to justify proceeding to phaseIII studies with trial designs as outlined in Figures 4aand 4b, it will be necessary to demonstrate safety of theagent, to assess pharmacokinetics, and to have somemeasure of desired biological activity, such as inhibi-tion of telomerase activity and shortening of telomerelength within tumour biopsy tissues (Table 1). It isoften not possible to gain pre- and post-therapybiopsies and so it is important either to study a patientgroup where tumour tissue is readily available, or toconsider other surrogate tissue in which telomeraseactivity can be assessed.The challenges presented in the evaluation oftelomerase therapies will therefore require an inte-grated laboratory and clinical approach, with arational clinical trial design incorporating biologicalendpoints. With careful consideration of both tumourbiology and the appropriate clinical scenarios, theintroduction of telomerase-based therapeutics into theclinic is awaited with great anticipation.AcknowledgementsThe Cancer Research Campaign (UK), the Scottish HospitalEndowments Research Trust (SHERT), the European Commis-sion and Glasgow University support research in the authors' lab.References1. Shay JW, Wright WE. Hayflick, his limit, and cellular ageing.Nature Rev Mol Cell Biol 2000; 1: 72?6.2. Reddel RR. A reassessment of the telomere hypothesis ofsenescence. Bioessays 1998; 20: 977?84.3. Reddel RR. The role of senescence and immortalization incarcinogenesis. Carcinogenesis 2000; 21: 477?84.4. Meyerson M. Role of telomerase in normal and cancer cells.J Clin Oncol 2000; 18: 2626?634.5. Holt SE, Shay JW. Role of telomerase in cellular proliferationand cancer. J Cell Physiol 1999; 180: 10?8.6. Shay JW, Zou Y, Hiyama E, Wright WE. Telomerase andcancer. Hum Mol Genet 2001; 10: 677?85.7. Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE.Stable association of hsp90 and p23, but not hsp70, with activehuman telomerase. J Biol Chem 2001; 276: 15571?5574.8. Holt SE, Aisner DL, Baur J, et al. Functional requirement ofp23 and Hsp90 in telomerase complexes. Genes Dev 1999; 13:817?26.9. Cuthbert AP, Bond J, Trott DA, et al. Telomerase repressorsequences on chromosome 3 and induction of permanentgrowth arrest in human breast cancer cells. J Natl Cancer Inst1999; 91: 37?5.10. Nishimoto A, Miura N, Horikawa I, et al. Functional evidencefor a telomerase repressor gene on human chromosome10p15.1. Oncogene 2001; 20: 828?35.11. Steenbergen RD, Kramer D, Meijer CJ, et al. Telomerasesuppression by chromosome 6 in a human papillomavirus type16-immortalized keratinocyte cell line and in a cervical cancercell line. J Natl Cancer Inst 2001; 93: 865?72.12. Ogoshi M, Le T, Shay JW, Taylor RS. In situ hybridizationanalysis of the expression of human telomerase RNA in normaland pathologic conditions of the skin. J Invest Dermatol 1998;110: 818?23.13. Ramirez RD, Wright WE, Shay JW, Taylor RS. Telomeraseactivity concentrates in the mitotically active segments ofhuman hair follicles. J Invest Dermatol 1997; 108: 113?17.14. Harle-Bachor C, Boukamp P. Telomerase activity in theregenerative basal layer of the epidermis in human skin and inimmortal and carcinoma-derived skin keratinocytes. Proc NatlAcad Sci U S A 1996; 93: 6476?481.15. Liu K, Hodes RJ, Weng N. Cutting edge: telomerase activationin human T lymphocytes does not require increase in telomerasereverse transcriptase (hTERT) protein but is associated withhTERT phosphorylation and nuclear translocation. J Immunol2001; 166: 4826?830.16. Liu K, Schoonmaker MM, Levine BL, June CH, Hodes RJ,Weng NP. Constitutive and regulated expression of telomerasereverse transcriptase (hTERT) in human lymphocytes. ProcNatl Acad Sci U S A 1999; 96: 5147?152.17. Brenner CA, Wolny YM, Adler RR, Cohen J. Alternativesplicing of the telomerase catalytic subunit in human oocytesand embryos. Mol Hum Reprod 1999; 5: 845?50.18. Albanell J, Bosl GJ, Reuter VE, et al. Telomerase activity ingerm cell cancers and mature teratomas. J Natl Cancer Inst1999; 91: 1321?326.19. Yashima K, Maitra A, Rogers BB, et al. Expression of theRNA component of telomerase during human development anddifferentiation. Cell Growth Differentiation 1998; 9: 805?13.20. 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