My name is Muhammad Shahbaz. I am from Pakistan. I am currently a master’s degree student, and my major is general surgery. I have been studying at Shandong University for the last 8 years. I am studying on CSC scholarship and I was awarded excellent graduate in 2011. During the study time at Shandong University, I was awarded the excellent student each year. Under the supervision of my tutor & mentor Prof. Niu Jun I have learned surgical skills and have actively participated in academic research work.

I also have learned Chinese language well during those years in China. I am the founder of a Charity Organization IECO (International Education Charity Organization). My stories were covered by Qilu Newspaper and Shandong Education TV. I was awarded from Jinan Municipal Government as excellent volunteer consecutively for last two years. I would like to be an academic surgeon in future.

During those years in China, I have also chaired the seminar for the junior students and have taught them about the research and clinical studies and how to pass the medical license exams of different countries. Three of my articles have been published in the China Daily Website, China Daily Website (Shandong Province) and My China Story, also a number of articles about my study life have been published on Shandong University Website.

Life means everything for us. And disease is the opposite of life. When we talk about disease, we are thinking of something against our health. We have spent and are spending much more money on medical research. Millions of people have been affected and are being affected every year. There are thousands of diseases. For hundreds of them, we have found cures via continuous striving in research. Scores of them are dangerous. A few of them are fatal. While we are thinking about the most dangerous diseases the first name that comes to mind is Cancer.

Since the mid-20th century, billions of dollars have been spent on cancer research and millions of research papers have been published on cancer. But the percentages of success have improved fractionally. The Chinese government is spending a lot of money on cancer research. On December 23, 1971, U.S. President Richard Nixon signed the National Cancer Act and declared “war on cancer” to amend the Public Health Service Act so as to strengthen the National Cancer Institute and more effectively carry out the national effort against cancer.

Every year, about15 million new cases of cancer appear, and 10 million people die of it around the world. We can either avoid and prevent the cancer or treat it. By now we have different methods of treatment of cancer, which are chemotherapy, immunotherapy, radiation therapy, surgery, adjuvant therapy, and transplantation. The main purpose of our research team was to find methods to make the treatment more effective, such as targeted therapies, which are drugs that interfere with specific molecules involved in cancer cell growth and survival. We tried to explore the precise information about the role that targeted therapies play in precision medicine and how targeted therapies work against cancer, who receives targeted therapies, common side effects, and what to expect when having targeted therapies.

The main members our team, including Liang Benjia, Gao Huijie, Fang Ruliang, Zhang Jia, Wu Junben, Niu Zhengchuan , Peng Cheng and myself, conducted the research under the supervision of Prof. Niu Jun. Prof. Niu has been working on novel and exciting research for the last two decades.

Last year, our team published eight SCI research papers with total impact factor of 30. I have published three SCI papers as first co-author and one SCI paper as second author with IF of 8.2. The motivation to perform this research was given by my mentor Prof. Niu Jun and some of the senior students.

From the very beginning of my undergraduate studies I started reading research papers, writing simple research and collecting data. After starting my master’s degree work, I was on the right path as Prof. Niu guided me and also broadened my viewpoint.

I still remember the year 2008, I was in the third year undergraduate MBBS program and the fellows in our class were taking the rabbits out of the cage. We were to observe the role of the arterial chemoreceptors and baroreceptors in the circulatory response to hypoxia of the rabbits. We used cell culture, RT-PCR techniques, Western blotting and immunohistochemistry, all the techniques I studied in my undergraduate years and later performed more specifically in postgraduate studies.

During my third year undergraduate studies I was curious to learn more research techniques and I also kept on attending international conferences. The first such a conference I attended in 2007, was the 21st International Congress of Lymphology and Oncology, where I presented research concerning patients having upper limb lymphoedema after breast cancer surgery. In the coming years I learned the knowledge about lymphology and oncology. In 2009 I attended the 22nd International Conference of Lymphology and Oncology and I won the best young scientist speaker award. I started to learn the research techniques more comprehensively, feeding the mice every day, changing the culture medium at the right time even in the holidays and systematically performing the tests, because delaying one step or getting one step late meant the whole procedure was disturbed and could have effects on the final results. So in order to avoid negative results we made sure that we can take care of mice and rabbits.

There is a famous saying that “I can have cancer but the cancer cannot have me”. In the process to find new methods of treatment and make the existing methods of treatment more effective, we conducted the research on a variety of cancers, which were mainly pancreatic cancer and colon cancer.

I joined our research team in the second year of my postgraduate studies in 2013 and we comprehensively conducted novel research about targeted therapy. I will discuss in detail the targeted therapy of our main research. The title of our research was “Integrinβ6-targeted Immunoliposomes Mediate Tumor Specific Drug Delivery and Enhance Therapeutic Efficacy in Colon Carcinoma”. It was published in the Clinical Cancer Research Journal in December, 2014, with SCI impact factor of 8.2. The other research articles by our team are "Comparison of the BISAP scores for predicting the severity of acute pancreatitis in Chinese patients according to the latest Atlanta classification” (SCI IF 2.2); “mRNA expression of somatostatin receptor subtypes SSTR-2, SSTR-3, and SSTR-5 and its significance in pancreatic cancer” (SCI IF 1.2); “Matrix Metalloproteinase Inhibitor MMI-166 Suppresses the Growth of SW1990 Human Pancreatic Cancer Cells” (SCI IF 0.5).

There are different kinds of ways we can contribute to scientific society. One is basic research, the second is translational medicine, and the third one is clinical research. The successful application of each method can improve the prognosis of disease. And we can also put different methods of treatment together in the form of adjuvant therapy to increase the efficacy of the treatment.

Colon cancer is the third most common cancer and the fourth-leading cause of cancer deaths worldwide. Although surgery remains the preferred treatment, 5-fluorouracil (5-FU)-based adjuvant chemotherapy is the conventional care for stage III (lymph node-positive) patients and can reduce mortality 25% compared with surgery alone. However, because the response rate of chemotherapy is only 10–20%, the treatment of advanced and metastatic cases remains a challenging problem. Therefore, it is urgent to explore novel therapeutic strategies for colon cancer treatment to overcome chemotherapeutic drug resistance and to improve chemotherapeutic efficacy.

The targeted delivery of anticancer drugs to tumors has been broadly recognized as an important method for improving chemotherapeutic efficacy and attenuating chemotherapeutic side effects. Sterically stabilized liposomes with a polymeric PEG coating, which have prolonged circulation times, lower reticuloendothelial system (RES) uptake and higher tumor accumulation, were thought to be an ideal drug delivery system. However, these liposomes passively interact with tumor cells, in vitro or in vivo, resulting in non-specific drug release that leads to the eventual diffusion of the drugs into some normal tissues or cells rather than tumors.

Immunoliposomes (ILs), which are conjugated with monoclonal antibodies (mAbs), are capable of both drug delivery and molecular targeting. By combining the specific targeting properties of mAbs and the drug delivery advantages of liposomes, ILs are a promising approach for the targeted delivery of anticancer drugs to tumors. To date, various tumor-associated antigens have been validated as targets for antibody-based ILs in cancer therapeutics.

ILs targeting CD30, HER2/neu, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptor (VEGFR), which are expressed on various tumor cell types, have been developed and thoroughly characterized. Based on encouraging preclinical data and advances in large-scale production processes, EGFR-specific ILs are already being used in clinical trials. Integrinβ6 (ITGB6) is a subtype of integrin that is expressed exclusively on the surfaces of epithelial cells and is a receptor for extracellular matrix (ECM) proteins. ITGB6 expression is up-regulated during embryogenesis, oncogenesis and epithelial repair, whereas it is generally undetectable in healthy epithelial tissues. In colon cancer, ITGB6 is specifically expressed in tumor tissues and is rarely present in tissues adjacent to the tumor.

Additionally, we previously reported that ITGB6 was associated with colon cancer pathology, malignancy and TNM stage and could act as a prognostic indicator in aggressive colon carcinomas. Our research previously confirmed that ITGB6 contributed to chemotherapeutic resistance in colon cancer; ITGB6 protected colon cancer cells from 5-FU-induced growth inhibition and apoptosis. Unsurprisingly, the exclusive expression of ITGB6 and its influential effects in colon cancer make it a novel therapeutic target for colon cancer treatment. ITGB6 has previously been employed as a clinical biomarker for early cancer detection.

Moreover, ITGB6 signaling axis-blocking agents have also been designed to exploit this receptor as a therapeutic target for cancer treatment. However, research concerning ITGB6 targeted drug delivery for colon cancer chemotherapy has not been reported. In the present study, we describe the design, preparation, and characterization of ITGB6-targeted ILs, and explore their antitumor efficiency against colon cancer in vitro and in tumor xenograft models using 5-FU loaded ITGB6-targeted ILs. The Translational Relevance of our research is that this study described a targeted drug delivery system for highly efficient and selective delivery of anticancer drugs in colon cancer overexpressing ITGB6. The ITGB6-targeted ILs achieved favorable antitumor efficacy and insignificant systemic toxicity, followed by specific binding and internalization in colon cancer cells.

As a result, this approach may be useful for the delivery of various drugs for enhanced therapeutic index against colon cancer. Moreover, because ITGB6 is also specifically expressed in a variety of epithelial carcinomas, ITGB6-targeted ILs may represent a potential strategy for the clinical treatment of additional cancers.

In my first year working towards my Master’s degree, besides learning subjects in basic theory I followed Prof. Niu Jun in the out-patient department and in the operation theater. I learned a number of surgical techniques including laparoscopic surgery, cholecystectomy, gastrectomy, whipple operation and thyroidectomy. Here I would like to mention one emotional story that I have mentioned in my story in the China Daily Website.

There were tears in my eyes, as the young girl told Professor Niu Jun, “Wo tong guo le,” which means “I passed the exam.” One month before, Sir. Niu Jun had told the patient, “You can participate in the Gaokao,” and it was the whole team of our General Surgery department headed by Prof. Niu Jun celebrating the happiness that we successfully operated on the seventeen years old girl with thyroid cancer metastasized to the lungs. She wanted to take the exam; it was on June 7, 2013. She had been admitted to our ward on May 15th. She had the option to come after the exam, or operate; however, as the cancer could spread to other parts of her body if she chose a later date, she opted to go for operation, to be done on May 20th. The successful surgery was done and she was able to speak within a few days of operation. She was discharged from hospital on May 27th, ten days before the exam.

Visiting L’Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), France, was also a great experience to learn about innovation, precision and minimally invasive surgery and robotic surgery. In April, 2007 Prof. Jacques was one of the surgeons of the team who successfully performed scarless surgery, also called as NOTES (Natural Orifice Translumenal Endoscopic Surgery); in this kind of surgery we approach the diseased part from the natural opening of human body, e.g. the mouth, or a anus, to resect the diseased organ and remove it through the natural opening. The technique was brought to China and the first such kind of operation was performed by a team of surgeons, gynecologists, and gastroenterologists headed by Prof. Niu Jun in 2009. I feel it my honor to learn minimally invasive surgery and modern precision surgery from the two best surgeons in the world.

The IHU Strasbourg and the IRCAD are unique facilities to learn modern techniques of modern surgery and operations. The future is based on known success. It was taught to me during a meeting with a professor. The new challenge in the modern medicine field is that our enemies (virus, bacteria and pathogens) are getting stronger and stronger and have gotten resistance against the drugs; and the diseases have become more severe and complicated while new infectious diseases and viruses erupt and are evolving with the modernization of human society.

In the modern era, precision surgery has evolved too. The visible patient is an original user-friendly online service for physicians who need a personalized 3D modelling of a patient to plan therapy efficiently, a project where we can use the CT, MRI, PACS scans of the patients to compile and combine them together using novel software to get the virtual 3D view of patients’ anatomy and internal organs. This can be used intraoperatively for planning the right surgical procedure and is beneficial and convenient for both doctors and patients. The use of Google glasses in advanced precision surgery and ultramodern computer software for the diagnostic imaging of the internal organs can also be used for the real time tracking of skin deformation, simulation of organ deformation and real time laparoscopic image analysis.

During my visit to IRCAD for training, I felt immense happiness to explore and learn about the modern techniques of diagnosis and treatment of diseases especially cancer. The future of surgery will be based on the image guided surgery via use of the techniques of virtual patients, preoperative simulation, intraoperative assistance, and combining augmented reality and robotics.

In the end I would like to acknowledge and pay my special thanks and regards to my professors, Prof.Niu Jun, Prof.Liu Zhiyu, Prof.Jia Jihui and Prof. Jiang Suhua. And special thanks for my parents, family and friends who helped and encouraged me during all these years. I would also like to encourage my fellows and junior medical students to put hands in hands and work hard; strive to defeat the cancer via every possible way we can.

Written byDr.Muhammad Shahbaz, Master Degree student of General Surgery on CSC Scholarship at Shandong University School of Medicine.

Source: School of Medicine