At the American Association for cancer research (AACR-IASLC) - International Association for cancer first conference on molecular origins of
At the American Association for cancer research (AACR-IASLC) - International Association for cancer first conference on molecular origins of lung cancer is organised on lung cancer research leaders stressed the importance of the research on basic scientific research and translational and clinical researchers cooperation.
According to this research, the project includes the study of the pathogenesis and clinical treatment. At a press conference, the person in charge of society to discuss a number of studies, including research topics include lung cancer diagnosis examination, smoking, genetic variation, and disease progression after Green Tea non Kyrgyzstan potential benefits of imatinib therapy retreatment patients, and erlotinib in the treatment of smokers. "This is an energetic time (for the study of liver cancer)," said Dr. AACR, President of Tyler, director of the David H.Koch Institute for cancer research at Massachusetts Institute of Technology. "We have found a number of important facts about how people should share these new findings and translate them into cancer patients as quickly as possible, which is critical," he said."
Early detection of blood
It is difficult for researchers to find the screening method suitable for early diagnosis of lung cancer is a problem, but a new blood test method to accurately detect lung cancer patients may change the status quo, make us closer to the target. The study was led by Dr. StevenDubinett, director of the lung cancer research program at the Jonsson comprehensive cancer center at David Geffen School of medicine, University of California, Losangeles, china.
"This study does suggest that using blood markers to detect and determine the feasibility of early lung cancer," Professor "although its accuracy has not reached the required level of clinical examination of the Dana-Farber Cancer Institute and the Broad Institute of Pathology, but I think the in-depth analysis of the study will make such a detection a clinical examination of value, we are full of expectations."
Dr Dubinett and his colleagues chose 40 kinds of serum proteins, and his own laboratory and other studies in the literature have suggested that these proteins are associated with lung cancer. Next, they used the antibody beads capture system to detect the expression level of each protein in 90 cases of stage I-IV lung cancer patients and 56 control subjects, all subjects were former smokers (30 years or longer), which belongs to the high risk of lung cancer. There were 21 kinds of proteins in I stage and control group. The accuracy of this group of proteins in the differential diagnosis of lung cancer 92%.
When the team used nearly 3 of the serum proteins (IL-2, IL-3, and macrophage derived chemokines), the blood test showed an accuracy of 93%, with a sensitivity and specificity of 97% and 77%, respectively.
The team collected 1072 blood samples before and after surgery for patients with benign pulmonary nodules, which were part of the ACOSOGZ4031 trial. In this study, 20% patients with benign nodal removal were enrolled in the study, and the researchers compared them as a control group for the accuracy of blood detection.
Vanderbilt-Ingram cancer center lung cancer specialized program of research and director of the HaroldL.Moses cancer research chairman Dr. DavidP.Carbone pointed out that required a high clinical value to check the sensitivity and specificity of screening population depends on.
"If you are screening for primary school students, the criteria used will be very different from those of high risk patients with severe smokers. My feeling is that they have reported sensitivity and specificity (if they are limited to a cohort of words), and high-risk individuals for lung cancer (for example, CT showed pulmonary nodules by people, has the guiding significance for)."
The conference co chair of the Carbone of the doctor in serum marks, he believes that ACOSOG in the study population of 20% benign nodules, even in the best center, this is a representative of the. Similar to the serum markers described by Dr. Dubinett and colleagues may reduce the risk of unnecessary surgery.
MinRNA differential diagnosis of small cell lung cancer
When the doctor Dubinett was trying to find the early diagnosis of NSCLC blood test, Scottdale medical center, Virgina G, PIPER director of cancer Lung Cancer Research Department of thoracic cancer center and applied genetics department deputy director Dr. GLENJ.WEISS and colleagues are looking for a way to identify the first-line chemotherapy in patients with small cell lung cancer. 30% of patients with small cell lung cancer are resistant to platinum based chemotherapy and have no other first-line treatment options.
"Not many new breakthrough in this part of patients, as an oncologist, I'm trying to find a new treatment, which may better than all take the same treatment," Dr. Weiss said in an interview. "If we can distinguish the standard chemotherapy resistant patients, then we will be able to distinguish these patients are new and may have better curative effect on the patients with first-line therapy clinical trials."
In order to find signs of primary drug resistance, Dr. Weiss and colleagues analyzed the miRNA features of 34 cases treated with standard chemotherapy in patients with tumor specimens, and 21 cases of CT data to assess them, of which 2 cases achieved complete remission, 13 cases partial remission, 2 cases of stable disease, 4 cases the progress of the disease.
Of the more than 1300 RNA genes contained in the microarray, the team found that the drug resistance was associated with one of the 16. When they were re examined with miRNA, 3 miRNA---miR-92a-2, miR-147, and miR-574-5p were significantly associated with primary chemotherapy resistance by RT-PCR. The team did not find any comorbidities and demographic characteristics that predicted resistance.
Dr Weiss's team is currently examining the role of these markers in a larger cohort of patients with small cell lung cancer, and is trying to understand the biological mechanisms underlying miRNA expression and drug resistance.
Dr. Jacks presented the study at the press conference. He said that although the study was small, the H needs to be validated in a larger study cohort, but miRNA did show a correlation with primary drug resistance.
Smoking, genetic polymorphism and green tea
Epidemiological data and laboratory studies suggest that green tea may reduce the risk of specific types of cancer in individuals. In order to better understand whether Green Tea can have an impact on the risk of lung cancer in Taiwan, Zhongshan medical university student I-Hsin Lin and students consider 170 cases of non-small cell lung cancer patients and 340 controls were drinking Green Tea. The team also examined the genetic polymorphism of the insulin-like growth factor genes (IGF1, IGF2, and IGFBP3) in participants, and tea polyphenols in green tea could cause changes in the expression of these genes.
The study participants completed a dietary questionnaire, including green tea consumption, smoking history, cooking habits and family history. Based on these data, Lin and colleagues found that people who did not drink green tea were 5.16 times more likely to develop lung cancer than those who drank up to 1 or more cups of green tea a day after being exposed to other risk factors.
The risk of lung cancer was increased to 12.71 times when green tea was not restricted to current or former smokers.
Interestingly, when the study group examined individuals with IGF1 and IGF2 genotypes, they found that participants with certain genetic polymorphisms were more likely to benefit from green tea than others. No variants of the IGFBP3 gene were found to be affected.
According to their data, the researchers speculate that green tea may reduce the risk of lung cancer, especially lung cancer caused by smoking, and some genetic variation can further affect this role.
Gefitinib again shows benefits
In a small study, the researchers found that the use of gefitinib in patients with non-small cell lung cancer after chemotherapy may be beneficial.
The study group consisted of Heshun hospital in Korea Chonnam University Assistant Professor In-jae Oh led the doctor, 18 patients with advanced or metastatic non-small cell lung cancer patients from these patients were recruited, the initial use of gefitinib treatment is effective, but after the disease progress and the subsequent packet received chemotherapy toxicity. Patients receiving gefitinib 250mg / D retreatment.
Of the 15 patients, 6 patients had partial remission, and the other had stable disease in 4 patients and disease progression in 2 patients. When the patients were divided into two groups: the first gefitinib treatment received partial remission and the disease was stable, the patients who received the first partial remission were more likely to get the curative effect in the second treatment.
In particular, in 6 patients who received partial remission in the initial treatment, there was a partial remission in the second group, and in 3 of the patients with stable disease. During the initial treatment period, only 9 of the patients with stable disease were treated with partial remission, and in the other 3 cases, the disease was stable in the treatment of 2 patients.
"The main reason for the progression of the disease still occur in long time after the relief is two the most common mutations, two mutations of the epidermal growth factor (EGF) gene is T790-M," executive director of IASLC, James Dudley, chairman of the University of Colorado cancer research medicine Professor Paul A.Bunn, said Dr. Jr.
"What kind of mutations lead to gefitinib or erlotinib and receptor binding is more difficult. However, only a small number of tumor cells occur, most of the tumor cells still contain the initial activation mutation. Therefore, there are two treatment methods. One of them is not very attractive but the feasibility is good, that is, given standard chemotherapy, usually those resistant cells are still sensitive to standard chemotherapy. When you finish chemotherapy, you can use again gefitinib or erlotinib. This is my current standard treatment." He noted that the data from South Korean researchers are consistent with previous reports from the Sloan-kettering Memorial cancer center in New York, suggesting that the use of gefitinib after 1 months intervals can reduce the size of most patients.
"So, I think it's really clinically significant," Dr. Bunn said, referring to a recent study of South korea.
In smokers increased dose of erlotinib
British researchers reported last year that smokers should be used more than non-smokers of erlotinib dose. Smoking increased the expression of cytochrome enzymes, these enzymes can cause erlotinib metabolism. In their study, the researchers found that the plasma concentrations of drugs and the skin rash in smokers who received 300mg treatment were similar to those of nonsmokers who had been treated with 150mg.
After these data, Lynsay L.Waller, a professor at the Wake Forest University Comprehensive Cancer Center in Winston-Salm, told the conference that it would be possible to deliver and gradually increase the dose of the drug according to smoking status.
The team has recruited 25 patients in a phase II study with the goal of recruiting a total of 50 patients. Current smokers receiving erlotinib for the treatment of the initial dose of 300mg / D, former smokers and non-smokers in the initial dose of 150mg / d. The researchers then increased the dose of 75mg every 2 weeks until the patient developed grade 2 hematologic toxicity. The dose was maintained at this level; the dose was reduced if the patient had 3 or grade 4 toxicities.
Up to now, the median maximum tolerated dose (MTD) of smokers was 300mg, while that of nonsmokers was 225mg. The dose range of smokers was 300-525mg, and non-smokers were 150-225mg. The toxicity of further improvement of the dose was prevented by the addition of grade 2 rash (23.5%), grade 2 diarrhea (grade 23.5%), grade 3 rash (grade 18%), grade 3 diarrhea (grade 18%), grade (6%), and disease progression (12%).
As patients continue to recruit patients, the researchers did not analyze the patient's response as the primary endpoint. However, the relief of doctor Weller high dose may improve smokers: "in the erlotinib approved before the initial study, they found that smokers to non-smokers without treatment so sensitive," she said.
This may be due to the activation of EGFR gene mutation in smokers with the possibility of a small, but this form of EGFR is very sensitive to erlotinib. "But the fact that smokers do not reach their MTD levels may also be partly responsible for the phenomenon."