Integrated Human Practice
Overview
In order to confirm our project is responsible for the society and ensure that we are working on the correct direction to push our project moving forward and contribute to the real world, we conducted different human practice activities and communicated with different resources.
Overview of our integrated human practice
Online Questionnaire
We published an online questionnaire focused on how much the common knowledge about glioma, TMZ, and TMZ resistance during the treatment of glioma. After we spread our questionnaire online, finally we received 432 completed questionnaires.
Basic information analysis
Figure 1. Gender, age and monthly income statistics of the respondents
Among the 432 persons, 45% is women and 55% is men, and 33% of people's age is around 18~35, 30% of people is around age 18 and under, 27% of people is around 35~65 years old, and 10% of people is 65 years old and above.
In term of the monthly income, 36% of people takes in 5000 RMB and under who might be students, 31% of people takes in 5000 RMB~10000 RMB each month who might be graduates or undergraduates, 15% of people received 20000 RMB~50000 RMB who might work for years, 11% of people gained 10000 RMB~20000 RMB every month who might be the young workers, and 7% of the people obtained 50000 RMB and above monthly who might be the senior workers.
Based on the analysis of the information above, it's appropriate to indicate that people who filled up our questionnaire equipped certain level of knowledge but not high-level intellectual persons, so the data of the questionnaire is able to reasonably show the knowledge level of the common people about glioma, TMZ, and TMZ resistance.
Focus analysis
Figure 2. Survey results of the questions “how much do you know about Temozolomide” and “how do you know about glioma?”
According to the survey result above, it's obvious to conclude that the knowledge level of the common about glioma, TMZ, and TMZ resistance is relatively low, which only 6% of people knowing glioma mostly because of the spread of network, new media, and introduction of popular science by friends and relatives. That means the social attention on glioma is relatively low because the influence of magazines, radio and television, and classes or lectures that are all formal is small, which also indicates the small number of articles, programs, channels, and classes published and established in the society, so social exposure of glioma is not that high let alone knowing the TMZ drug resistance.
Figure 3. Survey result of the question “do you think long-term use of temozolomide (TMZ) will lead to tumor resistance?”
Unquestionably, 51% of people who know glioma don't know about Temozolomide like Temodal, Tiqing, and Jiangning, and 58% of people gained information about Temozolomide through the introduction and popular science from friends and relatives. That indicates public traditional media including magazines and professional books don't pay much attention to the treatment of glioma related to TMZ, so the influence of those traditional media is not enormous enough to improve the knowledge level about TMZ of the common.
Above all, in one way we could create our own media channel and post related information for public education, in the other way we can cooperate with some influential press or media to publish educational articles or videos so as to increase the public attention or awareness of our concerned topic, glioma, and the TMZ drug resistance.
Field Trip
We took a field trip to patients who live in so-called "Cancer Village",actually some rental rooms for tumor patients around the Fudan University Cancer Hospital. Since most cancer patients require timely treatment, they usually choose to live near the hospital espectially those famous at cancer therapy which also results in the "Cancer Village" such a social phenomenon. From the environment where they live, we know that their lives are very tough. At the entrance of the hospital, there are also many people advertising related rental properties. Some people are still handing out flyers for recycling targeted drugs.
We interviewed patients who got the glioma. Most patients were pessimistic about their illness. They thought they might no live long after they develop drug resistance. Based on this concern, we realize that it is neccessary to solve this drug resistance issue which matters a lot for these patients even like life matters. We felt the responsibility that our project should take to help them.
Of course there are still a small number of patients who believe that their future is still bright and that they believe they can recover from this again. We expressed our caring and support to them and wish they can recover soon. Considering humanistic concern,we brought some fruits to the patients in Cancer Village to send our condolences to them.
We took visits to those patients and conducted interviews
Expert Interview
Back to our research, we were looking forward to the insights from those experts in relative areas so that we could review our topic and our project in a more objective way and further modify or improve our plans to proceed. Therefore, we managed to contact 4 experts in different areas.
1. Interview with Zhang Liang,professor and a doctoral supervisor of Shanghai Jiaotong Univeristy School of Medicine, the group leader of tumor chemical biology research group.
We conducted a series of interviews with Professor Zhang Liang online, and gained a lot of professional knowledge, which is of great help to our work.
Online meeting with Prof. Zhang Liang
First of all, our awareness of the causes of glioma, symptoms, and treatment, at present, the medicine does not know what it is made of induced, there are two kinds of hypothesis, one is that the brain by radiation, another is human body absorb pathogenic substances, If the cerebellar visual and primary nerves are compressed, their function may be lost. If the brain stem is compressed, the symptoms of headache and dizziness may occur. The current treatment options are drug chemotherapy, radiotherapy and surgical resection, but the recovery cycle of surgical resection is long and the sequelae are obvious
Second, we know that Temozolomide therapy works by giving the body a compound that, when it gets into the cell, inhibits the replication of the diseased cell and causes the diseased cell to die. In the medical community, Temozolomide is an irreplaceable ace drug, but its disadvantages are also obvious, its mechanism leads to its inability to recognize diseased cells and normal cells, has no targeting, and will destroy human healthy tissues
Third, we know that the principle of resistance is human body cell repair resistance, when it is damaged, can secrete a kind of didn't fix it is just like the sunshine, died not bask in the sun, ultraviolet radiation damage to the skin secrete repair, so as to timely repair, cancer cells have the same characteristics.
Fourth, introduced to professor sleeve cap, Temozolomide produced by major pharmaceutical companies at home and abroad has no obvious difference in drug resistance, because its chemical formula products are identical and its compound products have the same degree of metabolism. Patients will have drug resistance after taking the drug for a long time, but the effect is different
Fifth, Liang zhang, a professor at the research of new cancer drugs now have this view, drug research should be according to the pathological mechanism, explore the targeting property, find the reasons of normal cells into cancer cells, the first six, we asked, if our team created a kind of brand-new for Temozolomide amine resistance cell line, the scientific research team will buy, professor Liang zhang said, If the clinical use is consistent with the experimental results and the results are close to the clinical cases, it will be very marketable
Seventh, we asked how to successfully commercialize technology patents. The professor explained that it depends on the value of our products. Will customers buy our products? Whether our product can meet the market demand, the second is the uniqueness of the product, is not others unable to rule by law? Number eight, we also asked if cell lines could be patented and concluded that by applying through the Patent Office and getting a lawyer to write the application, we just provide the data and wait for a response. If successful you can seek a transfer to negotiate a price for selling this technology
Finally, we asked the professor now for Temozolomide drugs instead of amine, the professor said, now the world's major pharmaceutical companies are frantically for the development of new drugs, believe that will soon be listed in the future, people have been studying the mechanism of crack resistance, the first nine o 'clock, the professor explained the country and the government support to reduce tumor drug resistance study related policy, The state has special funds for national scientific research institutions and private research and development institutions to develop targeted drugs. Secondly, the state and enterprises can jointly establish projects to fund scientific research institutions. Actually in recent years, tens of billions of yuan has been allocated.
Above all, through this conversation with Prof. Zhang, we not only had a deeper understanding about glioma and Temozolomide therapy but also gained a clearer picture about the market.
2. Interview with Ye Mao, the production manager of an innovative public pharmaceutical company in Guangzhou
We interviewed Mr. Ye Mao, who graduated from Wuhan University of Technology with a degree in Pharmaceutical Engineering in 2008, worked for Fosun Pharmaceutical Group in Shanghai, and now works as a production manager for an innovative listed pharmaceutical company in Guangzhou. He specializes in the development and production of various dosage forms of pharmaceutical formulations, such as solid dosage forms, lyophilized dosage forms, liquid dosage forms, herbal extracts and APIs.
Online meeting with Mr. Ye
This interview brought us a lot of valuable information on drug production and its market. During the interview, Mr. Ye Mao mentioned a little special requirement in the development and production related to oncology drugs. In response to our questions regarding the position of TMZ in the market, and the gap between domestic and foreign TMZ brands, Mr. Ye gave the following answers.
"The products of tumor related drugs in China are very popular, one of the big reasons is its high death rate and low cure rate of tumors. And the side effects of common chemotherapy drugs will make us kill the cancer cells and normal cells at the same time. At this point in time, targeted drugs are important and very demanded."
He added, nowayds the most mainstream treatment method in the market now is gene therapy and the most popular drug used in gene therapy is Temozolomide (TMZ). Before the one-time evaluation of the drug in the last decade, the gap between domestic and foreign drugs was relatively large, but after the one-time evaluation of the drug, the efficacy of all drugs is similar. Although the efficacy is the same, these two models are used by different populations. Because of the complications of TMZ, some patients who have taken TMZ may develop symptoms of epilepsy, and such patients would not be suitable for the capsule and would use the injectable model of TMZ.
Professor Ye also answered questions related to the market value of our technology and the demand for it. He believes that the method of knocking down PGRG-1 used in our experiment is a relatively cutting-edge method in China. There are two methods of culturing cell lines that are routinely used now, the first is gradient culture and the second is high concentration pulse culture. The advantage of the first kind is that the drug resistance is stable but the process time is longer. The second type is more consistent with the in vivo drug uptake model, but at the same time, the stability of drug resistance is not as good as the first method. Nowadays, the oncology drugs developed in China mainly use large molecules and small molecules as raw materials, and the production purposes corresponding to these two raw materials are different.
For the more important cost aspect which is exactly where we were stuck in our business plan, Mr. Ye also provided us his opinion which inspired us a lot. He thought that most of the cost we should consider will be the spencing on R&D. And there is a scarcity of products on the market with the same positioning as our products, he suggested our future promotion shall focus on this selling point. After this conversation, we had more faith on our solution and its business value in the future market.
3、Interview with Zhu Yufang,the chief physician of neurosurgery at Shandong Cancer Hospital
On July 24, we conducted a telephone interview with Doctor Zhu Yufang who is the chief physician of neurosurgery at Shandong Cancer Hospital. This interview mainly focused on the pathological etiology, symptom classification, prognosis, survival period of glioma, existing clinical treatment plans, and the Chinese government's subsidy policy for related patients.
Photo of Doctor. Zhu Yufang
Regarding the cause of gliomas, Doctor Zhu mentioned there are mainly classified into genetic factors and environmental factors. If you have some genetic diseases, such as neurofibromas (type 1), tuberculous sclerosis, and so, it is easy to cause gliomas. Environmental factors are mainly related to electromagnetic radiation, such as long-term mobile phone use and working and living in a high radiation environment that may lead to gliomas. Gliomas can be classified into four grades according to their severity. In terms of prognosis and median survival time, the recovery rate of patients with this disease is not high. The median survival time for patients with grade 4 glioma was 14.6 months with less than 30% patients living to 2 years and less than 10% living to 5 years. The median survival time of patients with grade III glioma is about 2 years, and the median survival time of patients with grade II is 4-8 years. Generally, recurrence occurs in about 5 years. The five-year mortality of gliomas is only second to pancreatic and lung cancers.
TMZ is currently the most widely used glioma chemotherapy drug, but it is an alkylating agent and is prone to drug resistance. To Doctor Zhu's clinical experience, the way to decrease TMZ drug resistance mainly includes depletion of drug-resistant enzymes, increased drug density, and long-term chemotherapy. However, the effect of these measures is not very good and will cause great damage to the human body. Therefore, he agreed that if our experiment goes well and can be successfully used for drug development, it will have a very promising application future.
Doctor Zhu also introduced that the public's awareness of glioma is not high currently, so if it appeared poor prognosis of chemotherapy, many people will lose confidence, and even worsen the conditions of the disease. Therefore, it is very necessary to strengthen science popularization. In addition, due to the impact of Covid-19, China's medical resources have been tilted towards the anti-epidemic, so the burden of medical insurance has increased, which objectively adds some pressure to the treatment of glioma patients.
4、Interview with Li Wei, Associate Professor of Nanjing University and Associate Chief Physician of Neurosurgery Department of Nanjing Drum Tower Hospital
We also contacted another doctor Li Wei, who specializes in surgical treatment of cerebral hemorrhage, craniocerebral trauma, cerebrovascular disease, neurotumor and other diseases.
Online meeting with Dr. Li
According to Dr. Wei Li's clinical experience and our research, gliomas are primary tumors in the brain, and most of these are malignant and have a high incidence. There is no clear answer to the cause of the disease, but there are several hypotheses: congenital genetic predisposition, environmental factors (electromagnetic radiation, cell phones, and computers, environmental pollution). The most likely symptoms of brain tumors are localized brain loss, headache, nausea, vomiting, seizures, vision loss, facial paralysis, hearing loss, etc. Because of the different shapes and locations of brain tumors, the incidence of brain tumors is about one in 100,000 people. The incidence rate is about 6-8 per 100,000 people. Patients can be noted by some of the symptoms just described: functional decline in the body and edema. In addition, it can also be derived from MRI. The current clinical approach to glioma includes surgery, radiation therapy, chemotherapy, targeted therapy, or electric field therapy, depending on the patient.
Per his experience in clinical, TMZ is generally used for intermediate to high-grade gliomas: TMZ is also used for grade 3-4 meningiomas, and its efficacy is relatively reliable and can extend the life span of patients. Serious adverse reactions occur infrequently and there may be some blood cytopenia, drug allergy, and physical sensitization. If there is a significant reaction, discontinuation of the drug may be taken to test whether it is a drug problem. The emergence of drug resistance is relatively common. Different drugs are used for different patients, and the pathology is analyzed by removing the patient's tumor. Combination therapy, angiogenesis, cisplatin, electric field therapy, and other measures alternative regimens may be taken for drug resistance. The use of targeted drugs is currently not a mainstream approach. According to previous data, people can get gliomas at a young age. Usually, tumors appear in adults, and as they develop mutations in genes as they age, they appear in younger age groups, and appearing at an age when they should not be means that the changes in their bodies will be a more rapid and therefore higher grade.
The national funding for glioma drug development and treatment innovation has been increasing year by year in recent years. The medical insurance is very strong, which includes outpatient and TMZ medication costs, about 70%-80%. There is no special care for minors, just like most adults. It is worth noting that,there are some differences between the above statement on the state investment and the strength of medical insurance reimbursement and Doctor Zhu's view. Considering their different regions (one is in Jiangsu, the other is in Shandong), we believe that the differences in financial status and economic development level of different provinces might affect the government support policies for the treatment of glioma in local patients.
Team Meetups
The wet lab and dry lab closely communicates with each other on line at night after we finish that day’s tasks to catch up. In addition, we held around 3 offline seminars when both were available for reviewing the project progress. Increase the affections between the wet lab and dry lab to ensure the whole team in the same page.
The round-table meeting between wet lab and dry lab
In the first meeting, we communicated the ultimate goal of both teams and the tasks of both sides. The dry lab will be responsible for the business plan, the promotional video and organizing the charity sale in the early stage, while the wet lab was responsible for the technical research related to the experiment.
In the second meeting, we discussed the problems we encountered in the early stage. For example, the team members were a little constrained, and the communication will be a little estranged. So in this meeting, we sat together to spend more time talking to each other and promoted the team spirit.
At the third meeting, we exchanged the progress between the wet lab and dry lab, communicated the understanding deviation between us, and further came together to draw our team plan for the next step.