Hiroshi Nishihara

Observe, Examine, Understand, and Treat "Cancers"

Hiroshi Nishihara , Specially Appointed Professor

Graduate School of Medicine (School of Medicine, Department of Medicine)

High school : Toin Gakuen High School (Kanagawa)

Academic background : Hokkaido University Graduate School of Medicine

Research areas
Cancer pathology
Research keywords
Cancer, personalized diagnosis, experimental pathology, genome science, molecular biology

What is "Cancer"?

Figure 1  Macroscopic view of
adenocarcinoma occurring in the large intestine

Cancer is a disease in which cells that were originally components of the healthy body proliferate without limitation and destroy normal organs, causing functional failure. All malignant tumors are called “Cancer.” Among these, ones derived from the epithelial systems (such as mucosa and skin) are called carcinoma, and ones derived from mesenchymal systems (such as bones and muscles) are called sarcoma. Other cancers originating from the blood system are classified as "leukemia" or "malignant lymphoma.” In Japan, which has the world's highest longevity rate, it is now said that 1 in 3 people develop "cancer," and 1 in 2 die from "cancer.” Therefore, it is likely that one of your relatives has developed cancer. During the Edo-Meiji era, even though the average life span was around fifty years, the incidence of cancer was lower. Why has it increased so much during this current era? The answer is that medical science has advanced to the point where people do not die from diseases other than cancer. In other words, people suffer from cancer because of aging.


How do you diagnose "cancer"?

Figure 2  Tissue image of 
colorectal adenocarcinoma

We resect tissue from a patient through endoscopic examination or surgery to obtain a pathological tissue specimen, and observe cell morphology under a microscope to diagnose whether it is cancerous. This is our job as surgical pathologists. According to recent research, "cancer" occurs because of an accumulation of various gene abnormalities. These gene abnormalities are sometimes the same in certain kinds of "cancer." However, it was found that detailed abnormalities vary depending on individual patients. In other words, even for colorectal cancers that look the same, the characteristics of the cancer vary depending on the patient. Treatment of "cancer" has achieved remarkable progress due to the identification of these abnormal genes that cause cancer. In particular, with the advent of molecular targeted therapy drugs such as Iressa, treatment method options changed drastically, with some reported cases of lung or breast cancer being cured completely. Therefore, regarding the diagnosis of “cancer” in the future, it will be necessary to give a diagnosis patient-by-patient by inspecting gene abnormalities in detail.


What is the goal of your research?

What would you think if you were diagnosed with "cancer"? I guess you could not rid yourself of anxiety or fear, even if you were told that you could recover from the cancer completely by using the latest diagnostic instruments and methods, in addition to selecting a state-of-the-art treatment method. To overcome cancer, first of all, you need to know your cancer well. We aim to develop a next-generation pathological diagnosis system to make it possible to propose the best-suited treatment method for each particular patient. This will be achieved by inspecting and understanding gene abnormalities of "cancer" using a state-of-the-art inspection instrument such as a next-generation sequencer. Of course, we should not forget the traditional pathological method of observing "cancer" under a microscope.


What instruments do you use in your research?

Figure 3  Next generation sequencer
(Illumina MiSeq)

While we use a microscope to view pathological specimens, we extract nucleic acid such as DNA from the pathologic tissue to inspect "cancer" genes. A large number of nucleotide sequences from the extracted nucleic acid are analyzed simultaneously using a next generation sequencer to check for abnormalities of cancer-related genes. This instrument is a sequencer with high throughput and high accuracy that can finish decoding all human gene sequences within only several days, which took 10 years during the "Human Genome Project.” As this instrument is currently used mostly for research, we are trying to open the door to using this instrument as a daily diagnostic tool.

Figure 4  
Tumor formed under mouse skin.
The sizes are different due to the
difference of introduced genes
(red and yellow).

At the same time, we are validating whether these identified gene abnormalities are essential to cancer growth, and whether treatments targeting genetic abnormalities are truly effective. We introduce mutated genes into cultured cells using molecular biological techniques, and explore the mechanism of which molecules are related to the "cancer" growth. We inoculate the cancer cells under the skin of mice to induce tumors, and then administer anti-cancer drug to the mice and observe whether the tumors shrink.



What is your next goal?

We will not only research diagnostic and treatment processes for individual therapies, but also explain the steps to patients in a way that is easy to understand. Our goal is to provide medical services to make it possible for patients to live out their natural life spans, without dying due to “cancer in the now," by building a comprehensive pathological diagnostic system that may include mental support