A Research Team Led by Professor Jin Won Kim from the Department of Internal Medicine Develops Targeted Photoactivation Strategy for High-Risk Atheroma 

Joint Research Team (Left to right: Professor Jin Won Kim from the Cardiovascular Center at Korea University Guro Hospital, Professor Kyeongsoon Park from the Department of Systems Biotechnology at Chung-Ang University, and Professor Hongki Yoo from the Department of Mechanical Engineering at KAIST)

A joint research team led by Professor Jin Won Kim from the Cardiovascular Center at Korea University Guro Hospital, Professor Kyeongsoon Park from the Department of Systems Biotechnology at Chung-Ang University, and Professor Hongki Yoo from the Department of Mechanical Engineering at KAIST developed a targeted theranostic photoactivation strategy to detect and selectively treat high-risk arteriosclerotic plaques.

Phototherapy is a medical treatment in which the molecular mechanism inside cells is regulated by activating photosensitizers accumulated in cells using a specific wavelength of light. The research team developed a new theranostic agent by conjugating dextran sulfate (DS) to chlorin e6 (Ce6), which targeted a specific receptor in macrophages, and selectively delivered light energy to target lesions through a custom-built laser system  resulting in the reduction and stabilization of high-risk inflammatory plaques.

The phototheranostic agent was designed to obtain images at the same time as it treats, verifying the therapeutic effect in vivo through an optimized small animal optical imaging system (Figure 1), and it is revealed that induction of autophagy via photoactivation led to the efferocytosis of dead cells (Figure 1).

(Figure 1) A schematic diagram of the mechanism of action of the targeted phototherapy. Therapeutic effect was maximized by selectively transmitting the photosensitizer Ce6 and inducing photoactivity through laser irradiation by targeting macrophages in the high-risk arteriosclerotic atheroma.

Professor Kim, the lead author of the study, said, "The results of this study will explain the mechanism of phototherapy for arteriosclerosis and at the same time open the door to the development of novel diagnosis and treatment strategies using light in cardiovascular conditions. We are currently developing an integrated theranostic strategy that fully combines the catheter and targeted precision imaging technology, which is expected to help overcome the limitations of existing approaches that have the risk from the remnant foreign materials such as stent”

The study was published in the latest issue of Journal of Nanobiotechnology (2020 JCR IF 10.435), a renowned international journal, with Ph. D. Joon Woo Song from KUCM and Jae Won Ahn from Chung-Ang University as first authors. The research was conducted with support from the National Research Foundation of korea.

Professor Sung Gu Kang Introduces ‘Neurovascular Bundle Sparing Technique’ to Reduce Complication of Sexual Dysfunction After Prostatectomy

Introduces the toggling technique which allows retrograde early release to facilitate neurovascular bundle sparing with world-renowned Dr. Vipul Patel

Robot-assisted radical prostatectomy with the toggling technique can improve recovery of sexual function after surgery

Professor Sung Gu Kang from the Department of Urology at Korea University Anam Hospital introduced the toggling technique which allowed retrograde early release to facilitate neurovascular bundle sparing during surgery. This approach dramatically boosted the recovery of sexual function following prostatectomy. 

Professor Kang, together with Dr. Vipul Patel, a world-renowned doctor for his contribution to the field of robotic surgery especially for prostate cancer patients, conducted a study on the effect of retrograde early release approach for neurovascular bundle saving (toggling technique) on the recovery of erectile function. The study was published in the latest issue of Journal of Korean Medical Science.
 
The study revealed that Professor Kang's retrograde early release approach with the toggling technique could significantly boost the recovery from erectile dysfunction, one of the typical complications that could occur after conventional prostatectomy.

Those patients who underwent the robot-assisted radial prostatectomy with neurovascular bundle saving using the toggling technique had more than 10% better erectile function recovery compared to the other group without toggling. Overall, recovery of erectile function was 82% in the group with the toggling technique at the one-year follow-up.

Professor Kang said, “Advances in medical technology enabled us to perform minimally invasive surgeries using robots, which help enhance recovery while reducing complications. I believe this research not only demonstrates the excellent surgical technique that we have using robots for prostate cancer but also presents clinical evidence for minimally invasive surgeries. In addition, it can also facilitate recovery after surgery and help prostate cancer patients return to normal life sooner rather than later.”

Serving as a professor of urology at Korea University Anam Hospital, Dr. Kang is also a professor emeritus at the University of Central Florida Medical Center in the United States, well-known institution in the field of robotic surgery for prostate cancer, as well as an honorary professor at the Global Robotic Surgery Research Institute (GRI). He has utilized his skill and knowledge in this field to train and educate surgeons worldwide.

A Research Team Led by Professor Jong-Han Kim Reveals a New Chemotherapeutic Modality for Refractory Gastric Cancer with Peritoneal Metastasis

A multicenter prospective study on intraperitoneal anticancer treatment in patients with stage 4 gastric cancer with peritoneal metastasis conducted for the first time in Korea

Confirms recommended dose and safety of anticancer drugs administered into the peritoneal space combined systemic chemotherapy

A research team led by Professor Jong-Han Kim from the Division of Gastroenterological Surgery at Korea University Guro Hospital announced the results of a new systemic & intraperitoneal chemotherapy that can improve the survival rate of gastric cancer patients with peritoneal metastasis.

Professor Kim's team conducted a phase 1 study of intraperitoneal paclitaxel and oral S-1/oxaliplatin for advanced or recurrent gastric cancer with peritoneal metastasis. This study confirmed the recommended dose and safety of intraperitoneal paclitaxel administered with the systemic anticancer treatment.

Peritoneal metastasis is the most common type of metastasis and recurrence in patients with stage 4 advanced gastric cancer. In gastric cancer patients with distant metastasis, palliative systemic chemotherapy is the standard treatment, but even this has a very poor prognosis when peritoneal metastasis is present.

The research was a multicenter study involving more than 13 university hospitals in South Korea, and nine patients with stage 4 gastric cancer with peritoneal or distant metastasis received the treatment for approximately six months from June to December 2020. The subjects were divided into three groups to observe the progression after 40, 60, and 80 mg/㎡ of paclitaxel was administered into the peritoneal space respectively.

Phase I study confirmed that no serious side effects of grade 3 or higher were found in any of the patients participating in the study, and that peritoneal cancer index (PCI), which evaluates the degree of intraperitoneal metastasis decreased after chemotherapy.

Professor Kim said, "This research is a phase 1 multicenter study of intraperitoneal chemotherapy in stage 4 gastric cancer patients with peritoneal metastasis. Based on the results of this phase 1, a phase 2 study is currently implemented to prove its efficacy in enhancing survival. A phase 3 trial will be launched this year in order to confirm the survival rate compared to existing systemic chemotherapy."

He also said, "At present, only conventional palliative treatment is given to the gastric cancer patients with peritoneal metastasis because it is very difficult to treat and the benefit they could get from chemotherapy is very limited. Now, this study offers some hope for those patients with otherwise a fatal disease."

Professor Won Jun Seo from Korea University Guro Hospital and Professor Dong-Wook Kim from Dankook University Hospital participated as co-authors under the leadership of Professor Jong-Han Kim from Korea University Guro Hospital. Led by Professor You-Jin Jang, Korea University Guro Hospital along with 13 other centers in South Korea is currently running a phase 2 study. The results of the phase 1 study were published in the December 2021 issue of Journal of Gastric Cancer.

Biomarkers to Predict Response to Immunotherapy for Refractory Hepatocellular Carcinoma

A team led by Professor Jason Kyungha Sa (co-first author) from Korea University Graduate School of Medicine identified the molecular properties that determine the response to immune checkpoint inhibitors in liver cancer patients.

Hepatocellular carcinoma accounts for the majority of primary liver malignancy and is the fourth leading cause of cancer-related mortalities worldwide and it is known to have a high incidence in Asia.

Pembrolizumab, an immune checkpoint inhibitor, has been approved as a second-line treatment for hepatocellular carcinoma, but the identification of reliable biomarkers to predict the response to the treatment remained a major challenge.

The research team conducted an integrated multi-omics analyses of 60 hepatocellular carcinoma patients who received pembrolizumab to identify distinct genomic correlates that distinguish responders from non-responders.

Patients’ cancer tissue specimens were collected and genomic properties were characterized such as tumor microenvironment by assessing the results from whole-exome sequencing (WES), RNA and single-cell RNA sequencing.

This is to identify the primary cause of different effects of immunotherapy during treatment and to distinguish molecular biomarkers that can help identify those who are likely to benefit from the therapy.

The research team examined the differences by observing the patients' treatment process based on the results of high-precision analysis of the patients' genome. According to the research team, six out of the 60 hepatocellular carcinoma patients who received immunotherapy demonstrated partial response to the treatment, with an overall response rate of 10%. Clinical pathological analysis confirmed that female gender, PD-L1 positivity, and low neutrophil-to-lymphocyte ratio (NLR) were contributing factors to immunotherapy response.

On the other hand, somatic mutations in CTNNB1 and genomic amplifications in MET were found only in non-responders. Transcriptional profiles through RNA sequencing identified that responders demonstrated T cell receptor (TCR) signaling activation, indicating increased levels of T cell cytotoxicity induced response to immunotherapy.

In single-cell sequencing from 10 pre- and post-treatment peripheral blood mononuclear cells (PBMCs), patients who achieved a partial response or stable disease exhibited immunological shifts toward cytotoxic CD8+ T cells. Conversely, non-responders showed an increased number of both CD14+ and CD16+ monocytes and activation of neutrophil-associated pathways. Taken together, HCC patients with infiltration of cytotoxic T cells, along with increased active circulating CD8+ T cells and down-regulation of neutrophil-associated markers, significantly benefited from immunotherapy.

Professor Sa said, "The results of this study will help discover the next generation of immunotherapeutics for cancer patients who do not respond to the existing treatment modalities."

The study entitled "Hepatocellular carcinoma patients with high circulating cytotoxic T cells and intra-tumoral immune signature benefit from pembrolizumab: results from a single-arm phase 2 trial" was conducted along with Samsung Medical Center with support from the Research-Oriented Hospital Development R&D Project of the Ministry of Health and Welfare, and was published in the January issue of the international renowned journal, Genome Medicine (IF 11.117).