• 생약학회지
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• 제53권1호
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• pp.21-28
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• 2022

Sparassis crispa is an edible mushroom that has been widely utilized in Japan and Korea. It has various biological activities, such as anti-hypertensive, anti-allergic, anti-diabetic, anti-inflammatory, anti-angiogenic, and anti-cancer effects. In this study, we investigated the anticancer activity and underlying molecular mechanism of chloroform fraction of methanol extract of S. crispa (CESP) against cervical cancer stem cells (CSCs), which contribute to tumor initiation, recurrence, and resistance to therapy of human cervical cancer. CESP effectively inhibited the proliferation, tumorsphere formation, and migration of HeLa-derived cervical CSCs by promoting apoptosis. In addition, CESP significantly downregulated the expression of key cancer stemness markers, including integrin α6, CD133, CD44, ALDH1A1, Nanog, Oct-4, and Sox-2, in HeLa-derived cervical CSCs. Furthermore, CESP remarkably suppressed in vivo tumor growth of HeLa-derived cervical CSCs in a chick embryo chorioallantoic membrane (CAM) model. Therefore, our findings suggest that CESP has potential as a natural medicine for the prevention and treatment of cervical cancer by targeting CSCs.

• Journal of Gastric Cancer
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• 제23권3호
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• pp.410-427
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• 2023

Recent advances in artificial intelligence (AI) have provided novel tools for rapid and precise pathologic diagnosis. The introduction of digital pathology has enabled the acquisition of scanned slide images that are essential for the application of AI. The application of AI for improved pathologic diagnosis includes the error-free detection of potentially negligible lesions, such as a minute focus of metastatic tumor cells in lymph nodes, the accurate diagnosis of potentially controversial histologic findings, such as very well-differentiated carcinomas mimicking normal epithelial tissues, and the pathological subtyping of the cancers. Additionally, the utilization of AI algorithms enables the precise decision of the score of immunohistochemical markers for targeted therapies, such as human epidermal growth factor receptor 2 and programmed death-ligand 1. Studies have revealed that AI assistance can reduce the discordance of interpretation between pathologists and more accurately predict clinical outcomes. Several approaches have been employed to develop novel biomarkers from histologic images using AI. Moreover, AI-assisted analysis of the cancer microenvironment showed that the distribution of tumor-infiltrating lymphocytes was related to the response to the immune checkpoint inhibitor therapy, emphasizing its value as a biomarker. As numerous studies have demonstrated the significance of AI-assisted interpretation and biomarker development, the AI-based approach will advance diagnostic pathology.

• 대한한방내과학회지
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• 제44권4호
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• pp.765-773
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• 2023

Objective: This long-term case report details a case of pancreatic cancer with lung metastasis suppressed by integrative cancer medicine (IMT). Methods: A 64-year-old woman diagnosed with pancreatic cancer visited a Korean medicine hospital complaining about the side effects of chemotherapy for lung metastasis. She received IMT involving Korean traditional medicine and Western immunotherapy from May 2017 to June 2023. Tumor dimensions were assessed through computed tomography (CT) and positron-emission tomography/CT scans, while tumor markers and safety were monitored by laboratory tests. Results: IMT suppressed the progression of cancer, as observed by imaging and laboratory tests. The patient achieved 5-year survival, even after discontinuing chemotherapy. Conclusion: This case presents a potential therapeutic alternative for patients who are ineligible for chemotherapy or surgical interventions.

• Korean Journal of Radiology
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• 제22권10호
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• pp.1650-1657
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• 2021

Metastatic mature teratoma is a common radiologic and histopathologic finding after chemotherapy for metastatic non-seminomatous germ cell tumors. The leading theory for these residual tumors is the selective chemotherapy resistance of teratomas versus the high chemotherapy sensitivity of the embryonal components. Growing teratoma syndrome is a relatively rare phenomenon defined as an enlarging residual mass histologically proven to be a mature teratoma in the setting of normal serum tumor markers. Metastatic mature teratomas should be resected because of their malignant potential and occasional progression to growing teratoma syndrome with the invasion of the surrounding structures. CT is the preferred imaging modality for post-chemotherapy surveillance and should cover all sites of potential metastatic disease. This article reviews the clinical, pathologic, and multimodality imaging features of metastatic mature teratomas in patients with primary testicular non-seminomatous germ cell tumors.

• 대한한방내과학회지
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• 제44권6호
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• pp.1346-1353
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• 2023

Objectives: This long-term case report presents the case of an ovarian cancer patient with brain, cervical lymph node, and vertebral metastasis suppressed by traditional Korean medicine in combination with cytokine-induced killer (CIK) cell-based immunotherapy. Methods: The patient received acupuncture, moxibustion, GunChil-go, Hangam-dan, and CIK cell-based immunotherapy. The Eastern Cooperative Oncology Group and tumor markers were used to evaluate the treatment effects. Results: Integrative cancer treatment suppressed the progression of cancer, and the patient achieved eight-year survival. The performance status improved, and the tumor marker level was maintained. Conclusions: We suggest that an integrative cancer treatment that includes traditional Korean medicine can be a meaningful treatment option for advanced ovarian cancer.

• Biomolecules & Therapeutics
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• 제32권5호
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• pp.556-567
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• 2024

β-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble β-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived β-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.

• Radiation Oncology Journal
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• 제24권2호
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• pp.128-137
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• 2006

목적: 방사선 감수성이 다양한 동계(syngeneic) 마우스 종양들을 대상으로 50% 종양억제선량과 종양성장지연 등 방사선 감수성을 대변하는 지표와 방사선에 의해 유도되는 아포토시스 간에 상관관계가 있는지 여부를 알아보고자 하였다. 또한 아포토시스와 관련된 여러 유전물질의 기본(constitutive) 발현수준을 측정한 후 이들 상호 간의 상관관계를 분석하여 방사선 감수성을 예측할 수 있는 생물학적 표지자를 알아보고자 하였다. 대상 및 방법: 동계 마우스 종양으로는 난소암 OCa-1, 유방암 MCa-K, 편평상피세포암 SCC-VII, 섬유육종 FSa-II, 간암 HCa-1을 사용하였고 이들은 PCR-SSCP 검사상 p53이 모두 자연형인 종양들이었고 주령 $8{\sim}10$ 주인 C3H/HeJ 웅성 마우스를 사용하였다. 50% 종양억제선량과 종양성장지연 및 방사선에 의해 유도되는 아포토시스를 측정하여 이들과 방사선에 의해 유도되는 아포토시스간의 상관관계를 분석하여 방사선에 의해 유도되는 아포토시스로 방사선 감수성을 예측할 수 있는지 여부를 알아보고, 또한 아포토시스와 관련된 유전물질 $053,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-x_L,\;Bcl-X_s,\;p34$ 등의 기본 발현양상 및 발현수준을 Western blot과 농도계측기로 측정한 후 이들 상호 간의 상관관계를 분석하였다. 결과: 방사선에 의해 유도된 아포토시스의 정도와 종양성장지연과의 사이에는 통계적으로 유의한 상관관계가 존재하였다(R=0.922, p=0.026). 50% 종양억제선량과의 사이에는 통계적 유의성은 변연수준이었으나(p=0.070) 상관관계의 경향을 보였다(R=-0.848). $p21^{WAF1/CIP1}$과 p34의 기본 발현수준과 50% 종양억제선량(R=0.893, p=0.041와 R=0.904, p=0.035) 및 종양성장지연(R=-0.922, p=0.026와 R=-0.890, p=0.043) 사이에는 통계적으로 유의한 상관관계가 존재하였다. 즉, $p21^{WAF1/CIP1}$과 p34의 기본 발현수준이 낮은 경우에 방사선 감수성이 높고, 기본 발현수준이 높은 경우에는 방사선 감수성이 낮은 상관관계가 존재함을 알 수 있었다. 결론: 방사선에 의해 유도된 아포토시스의 정도로 종양의 방사선 감수성을 예측하여 볼 수 있을 것으로 생각하며, 종양의 방사선 감수성을 예측할 수 있는 생물학적 표지자로 $p21^{WAF1/CIP1}$와 p34의 기본 발현수준이 이용될 수 있을 것으로 생각한다.

• Tuberculosis and Respiratory Diseases
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• 제46권4호
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• pp.523-532
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• 1999

연구배경: 폐암은 조기진단이 어려운 대표적인 종양이다. 최근 정상세포에서 악성조직으로 진행되는 각각의 과정에 대한 연구가 활발해 지면서 폐암의 발병과 진행에 관계하는 여러 유전자와 염색체의 이상들이 발견되고 있다. 이에 근거하여 폐암 중에서도 객담 세포진검사나 기관지내시경 검사 등으로 진단이 용이하고, 조기진단의 의의가 높은 편평상피 폐암을 대상으로 종양세포와 인접 정상 세포에서의 p53 및 c-erbB2의 발현율과 그 의의를 알아보았다. 대상 및 방법: 1995년 5월부터 1996년 11월까지 15개월 동안 편평상피 폐암으로 진단되어 폐절제술을 받은 25명의 환자를 대상으로 하여, 종양부위 및 그 인접 정상세포에서의 p53과 c-erbB2의 발현 여부를 면역조직화학적 검사법을 이용하여 조사하고 폐암의 병리적 병기 및 환자의 생존기간에 따른 발현율의 차이를 후향적으로 조사하였다. 결 과: 25명의 환자 중에서 병리적 병기 I, II가 각각 5명, IIIA가 8명, IIIB가 4명 및 IV가 3명이었다. 종양조직에서의 p53은 12명(48%), erb-B2는 3명(12%)에서 발현되었다. 인접 정상 기관지세포에서는 erb-B2는 3명(12%)에서 발현되었으나 p53은 한 예에서도 발현되지 않았다. 종양세포에서, 병기 II기 이하인 군 10명과 IIIA기 8명 및 IIIB와 IV기의 7명으로 나눠서 비교한 결과 p53이 발현된 경우는 각각 2예, 4예 및 6예로 병기가 진행될수록 발현율은 유의하게 높아졌다(p=0.009 by test of trend). 그러나 종양세포에서 이들의 발현여부에 따른 생존기간은 차이가 없었다. 결 론: p53은 정상 기관지세포에서는 전례에서 발현되지 않았으나 페종양조직에서는 발현율이 48%로 나왔으며, 발현율은 병기가 진행할수록 높아졌다. 따라서 기관지 생검조직에 p53을 이용한 면역조직화학적검사를 병행할 경우 편평상피세포 폐암의 경우 조기진단이나 병기판정에 도움이 될 것으로 추정되나 더 많은 환자를 대상으로 한 연구가 필요할 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7039-7044
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• 2015

Background: Many functional molecules controlling diverse cellular function are included in low-molecular weight proteins and peptides. Materials and Methods: To identify proteins controlling function in lung adenocarcinomas (AC), we performed two-dimensional gel electrophoresis employing tricine-SDS polyacrylamide in the second dimension (tricine 2-DE). This system was able to detect proteins under 1 kDa even with post-translational modifications. To confirm the utility of detected proteins as novel tumor markers for AC, we performed immunohistochemical analysis using 170 formalin-fixed and paraffin-embedded lung AC tissues. Results: Tricine 2-DE revealed that five proteins including S100A16 were overexpressed in lung AC-derived cells compared with lung squamous cell carcinoma, small cell carcinoma, and large cell neuroendocrine carcinoma-derived cells. Immunohistochemically, S100A16 showed various subcellular localization in lung cancer tissues and a membranous staining status was correlated with the T-factor (P=0.0008), pathological stage (P=0.0015), differentiation extent (P=0.0001), lymphatic invasion (P=0.0007), vascular invasion (P=0.0001), pleural invasion (P=0.0087), and gender (P=0.039), but not with the age or smoking history. More importantly, membranous staining of S100A16 was significantly correlated with a poorer overall survival of either stage I (P=0.0088) or stage II / III (P=0.0003) lung AC patients, and multivariate analysis confirmed that membranous expression of S100A16 was an independent adverse prognostic indicator (P=0.0001). Conclusions: The present results suggest that S100A16 protein is a novel prognostic marker for lung AC.

• 대한핵의학회지
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• 제22권1호
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• pp.83-92
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• 1988

The cocktails of two $^{131}I$ labeled Monoclonal antibody (MCAB) (Anti CA 19-9 F$(ab')_2$ + Anti CEA $F(ab')_2$ fragment), which react specially, with human gastrointestinal cancers, were administered to 10 patients with colorectal (7), stomach(2) and pancreas(1) cancer for scintigraphic detection. All patients were known or postoperatively recurrent cases, and serum tumor markers, CA 19-9 and CEA, were measured with immunoradiometric assay, just before immunoscintigraphy (ISG). The tumor marker's level in serum is not correlated with positive tumor uptake in ISG. The sensitivity and specificity of ISG in detection of 21 tumor sites, based on surgery, CT, ultrasonography and pathology, were 90.5% and 100% One case of colon cancer showed gall bladder metastasis, which was neglected on CT study. Tumor/non tumor uptake ratio of radiolabelled antibody were progressively increased from day 3 to day 7 during study. We summerized as follows 1) The use of cocktails of CEA and CA 19-9 MCAB $F(at')_2$ increased sensitivity and specificity in ISG. 2) Delayed imaging (later than 5 days) increases sensitivitv and specificity due to exclusion of nonspecific iodine accumulation in stomach and lung. 3) Second tracer technique is essential for anatomical landmark by use of a double isotope scan, but subtraction technique, a possible source of artifacts, is no longer necessory when delayed imaging is performed. 4) It may be possible to use two MCAB cocktails of CA 19-9 and CEA in Radioimmunodetection of stomach and pancreas cancer. In conclusion, ISG using MCAB cocktails, $F(ab')_2$ fragment of anti CA 19-9 and Anti CEA, provide additional opportunity for tumor localization and detection of colorectal and other G-I cancer, such as stomach and pancreas.