Prognostic implications of PD-L1 expression in patients with angiosarcoma

Aim: There are limited data on the feasibility of programmed death ligand-1 (PD-L1) expression as a prognostic biomarker in metastatic angiosarcoma. Patients & methods: We retrospectively collected and analyzed the data on PD-L1 expression in 70 angiosarcoma patients who were diagnosed at our center between 2005 and 2019. Results: Thirteen (19%) patients had PD-L1 expression. Metastatic angiosarcoma patients who were PD-L1-negative (n = 24) showed longer median progression-free survival (4.9 vs 1.6 months; p = 0.04) and median overall survival (OS; 10.9 vs 5.4 months; p = 0.01) than those who were PD-L1-positive (n = 4). PD-L1 status proved to be a significant factor for OS. Conclusion: Metastatic angiosarcoma patients with PD-L1 expression showed shorter survival. PD-L1 status is an independent prognostic factor for OS in metastatic angiosarcoma patients.ope

PD-L1 tumour expression is predictive of pazopanib response in soft tissue sarcoma

Background: Pazopanib, a multitargeted tyrosine kinase inhibitor, is recommended as the standard treatment for refractory soft tissue sarcoma (STS). However, there are comparatively few molecular determinants for predicting pazopanib efficacy. Based on correlative studies regarding the predictive impact of PD-L1, we investigated the clinical relevance of PD-L1 expression and evaluated its value for predicting pazopanib efficacy. Methods: Tumour tissues from patients with advanced STS who went on to receive pazopanib were assessed for PD-L1 expression. Immunohistochemistry was performed using an anti-PD-L1 antibody, and the PD-L1 tumour proportion score (TPS) was calculated as the percentage of at least 100 viable cells with positive expression, defined as TPS ≥ 1%. Results: Among the 67 patients, 8 (11.9%) achieved partial response and a median progression-free survival (PFS) of 4.8 months (95% CI 3.8-5.7). PD-L1 expression in tumour cells was detected in 13 (19.4%) cases and the TPS scores ranged from 1 to 100%, as follows: 0 (n = 54, 80.6%), 1-9% (n = 3, 4.5%), 10-49% (n = 9, 13.4%), and ≥ 50% (n = 1, 1.5%). PD-L1 positive tumours exhibited a poorer response to pazopanib treatment than the PD-L1 negative tumours (0% vs 14.8%, P = 0.07). PD-L1-positive tumours had significantly shorter PFS than the PD-L1-negative tumours (median PFS 2.8 vs 5.1 months, P = 0.003), and PD-L1 positivity was an independent predictor of poor response to pazopanib treatment (HR 2.77, 95% CI; 1.45-5.56, P = 0.006). Conclusion: We identified that PD-L1 expression can help predict the clinical outcome of patients with advanced STS treated with pazopanib. Based on our study, stratification should be actively considered in order to identify patients who will benefit from pazopanib or further therapeutic strategies for future clinical trials.ope

Genomic landscape of extraordinary responses in metastatic breast cancer

Extreme responders to anticancer therapy are rare among advanced breast cancer patients. Researchers, however, have yet to investigate treatment responses therein on the whole exome level. We performed whole exome analysis to characterize the genomic landscape of extreme responders among metastatic breast cancer patients. Clinical samples were obtained from breast cancer patients who showed exceptional responses to anti-HER2 therapy or hormonal therapy and from those who did not. Matched breast tumor tissue (somatic DNA) and blood samples (germline DNA) were collected from a total of 30 responders and 15 non-responders. Whole exome sequencing using Illumina HiSeq2500 was performed for all 45 patients (90 samples). Somatic single nucleotide variants (SNVs), indels, and copy number variants (CNVs) were identified for the genomes of each patient. Group-specific somatic variants and mutational burden were statistically analyzed. Sequencing of cancer exomes for all patients revealed 1839 somatic SNVs (1661 missense, 120 nonsense, 43 splice-site, 15 start/stop-lost) and 368 insertions/deletions (273 frameshift, 95 in-frame), with a median of 0.7 mutations per megabase (range, 0.08 to 4.2 mutations per megabase). Responders harbored a significantly lower nonsynonymous mutational burden (median, 26 vs. 59, P = 0.02) and fewer CNVs (median 13.6 vs. 97.7, P = 0.05) than non-responders. Multivariate analyses of factors influencing progression-free survival showed that a high mutational burden and visceral metastases were significantly related with disease progression. Extreme responders to treatment for metastatic breast cancer are characterized by fewer nonsynonymous mutations and CNVs.ope

대장 MALT 림프종의 내시경소견과 임상양상

배경: 대장의 점막연관림프조직 림프종은 비교적 드문 질환으로 진단 및 치료 전략이 명확히 정립되어 있지 않다. 이 연구를 통해 대장의 점막연관림프조직 림프종의 임상 소견 및 내시경적 특징을 확인해보고자 하였다. 방법: 2002년 1월부터 2016년 5월까지 서울아산병원에서 대장의 점막연관림프조직 림프종으로 진단받은 환자를 대상으로 임상자료를 후향적으로 분석하여 치료 경과 등 임상적 특징을 조사하였다. 대장내시경 사진을 검토하여 대장 점막연관림프조직 림프종의 내시경적 특성을 분석하였다. 결과: 51명의 환자를 분석하였고, 중간 연령은 60세 (IQR 55-71 세)였다. 남성이 21명(41.2%)이었다. 26명의 환자(51 %)는 증상이 없었으나 정기적인 추적관찰을 통해 진단되었고, 44예 (86.3%)가 임상적으로 초기 병기에 진단되었다 (Ann-Arbor 병기 IE 및 IIE). 내시경 소견은 1) 상피종양 유형(26예, 51.0%), 2) 폴립증 유형(10, 19.6%), 3) 보르만 I 유형(7, 13.7%), 4) 회장염 유형(8, 15.7%)의 4가지 유형으로 분류할 수 있었다. 대장 점막연관림프조직 림프종은 직장(20, 39.2%)에서 가장 흔히 발견되었고, 회맹부(15, 29.4%)가 두번째로 흔하게 침범된 부위였다. 내시경 소견만으로 점막연관림프조직 림프종을 의심한 환자는 7명에 불과했다. 35명의 환자에서 초기 조직 획득 방법으로 겸자 생검이 시행되었으며, 그 중 28명(80%)에서 조직학적으로 점막연관림프조직 림프종이 진단되었다. 조직학적 진단을 위한 검사법으로 폴립절제술을 처음부터 시행한 16명의 환자들은 모두 폴립절제술 검체로 점막연관림프조직 림프종의 진단이 가능하였다. 내시경절제술, 수술, 방사선치료, 항암화학요법, 경과 관찰 등 다양한 치료가 시행되었고, 5년 비진행 생존율과 5년 전체 생존율은 각각 92%와 94%였다. 결론: 대장 점막연관림프조직 림프종은 다양한 내시경 소견을 보였으며, 따라서, 내시경 소견만으로 대장 점막연관림프조직 림프종을 의심하기는 어려웠다. 대장 점막연관림프조직 림프종의 예후는 우수하였다 |BACKGROUND & AIMS: Colorectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease. The purpose of this study was to investigate the clinical and endoscopic features of colorectal MALT lymphoma. METHODS: Patients diagnosed with colorectal MALT lymphoma at Asan Medical Center from 2002 to 2016 were eligible. Medical records were reviewed to investigate clinical features and treatment outcomes. Endoscopic pictures were assessed to characterize the endoscopic features of colorectal MALT lymphoma. RESULTS: A total of 51 patients were enrolled. The median age was 60 years (interquartile range, 55–71) and 21 (41.2%) were male. Twenty-six patients (51%) were asymptomatic. Forty-four patients (86.3%) were in early disease stages, namely, Ann Arbor IE and IIE. Endoscopic appearances were classified as 4 distinct types: (1) subepithelial tumor type (26 patients, 51.0%); (2) polyposis type (10 patients, 19.6%); (3) Borrmann I type (7 patients, 13.7%); and (4) ileitis type (8 patients, 15.7%). The rectum (20 patients, 39.2%) was the most common location, followed by the ileocecal area (15 patients, 29.4%). An initial endoscopic impression of lymphoma was made in only 7 patients. Forceps biopsy as the initial tissue acquisition method could histologically diagnose MALT lymphoma in 28 of 35 patients (80%). Polypectomy as the initial histological diagnosis could diagnose MALT lymphoma in 16 of 16 patients. Treatments included endoscopic resection, surgery, radiotherapy, chemotherapy, and observation. Progression-free and overall survivals at 5 years were 92% and 94%, respectively. CONCLUSIONS: Colorectal MALT lymphomas show various endoscopic appearances, complicating the endoscopic suspicion of colorectal MALT lymphoma. The prognosis of colorectal MALT lymphoma was excellent.Maste

A method for stimulating antigen specific cytotoxic T lymphocyte in large scale using dendritic cells

본 발명은 수지상 세포를 이용한 대량의 항원 특이적 CTL(Cytotoxic T Lymphocyte) 유도 방법에 관한 것으로, 구체적으로 HLA-A 유형이 같은 동종의 수지상 세포에 항원을 적재한 후, 림프구와 공배양함으로써 항원 특이적 CTL을 유도하는 방법 및 상기 수지상 세포를 포함하는 면역 치료 및 예방용 백신에 관한 것이다. 본 발명에 따른 CTL 유도 방법 및 면역 치료 및 예방용 백신은 HLA-A 유형이 같은 환자의 질병 치료에 필요한 항원 특이적 CTL을 효과적으로 유도할 수 있어 면역세포 치료에 효과적으로 사용될 수 있다

Bcl−xL/Bcl−2Bcl-x_{L}/Bcl-2의 과발현과 LDH-A의 저발현이 CHO 세포의 배양에 미치는 영향

학위논문(박사) - 한국과학기술원 : 생명과학과, 2011.8, [ x, 92 p. ]한국과학기술원 : 생명과학과

Pemetrexed plus cisplatin in patients with previously treated advanced sarcoma: a multicenter, single-arm, phase II trial

Background: Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. We assessed the efficacy and tolerability of pemetrexed and cisplatin combination therapy in patients with refractory bone and soft tissue sarcoma (STS). Patients and methods: Patients were included in this multicenter, phase II study (ClinicalTrials.gov identifier NCT03809637) if they progressed after receiving one or more chemotherapy regimens containing an anthracycline and/or ifosfamide. Pemetrexed was first administered intravenously, followed by cisplatin, over a cycle of 21 days, for a maximum of six cycles. The primary endpoint was a progression-free rate (PFR) at 3 months (3-month PFR). Results: From January 2017 to September 2019, we enrolled 37 patients; of these, 73% had previously undergone three or more rounds of chemotherapy. Five patients (13.5%) exhibited objective responses, including two patients (2/6, 33.3%) with malignant peripheral nerve sheath tumors, one patient (1/4, 25%) with synovial sarcoma, one patient (1/4, 25%) with undifferentiated pleomorphic sarcoma, and one patient (1/4, 25%) with angiosarcoma. The median progression-free survival was 2.6 months, and the 3-month PFR was 45.9% (n = 17). None of the four patients with osteosarcoma exhibited objective responses or were progression free at 3 months. The most frequent treatment-related grade 3-4 toxicities included neutropenia (16.2%), anemia (13.5%), thrombocytopenia (13.5%), and fatigue (8.1%). Among 26 patients (70.3%) available for immunohistochemical assessments, patients in the low-excision repair cross-complementation group 1 (ERCC1) and low-thymidylate synthase expression groups showed a tendency for longer overall survival. Conclusions: Combination therapy with pemetrexed and cisplatin was associated with clinically meaningful and sustained responses among patients with advanced and refractory STS. The combination therapy met its predefined primary study endpoint.ope

PD-L1 tumour expression is predictive of pazopanib response in soft tissue sarcoma

Background: Pazopanib, a multitargeted tyrosine kinase inhibitor, is recommended as the standard treatment for refractory soft tissue sarcoma (STS). However, there are comparatively few molecular determinants for predicting pazopanib efficacy. Based on correlative studies regarding the predictive impact of PD-L1, we investigated the clinical relevance of PD-L1 expression and evaluated its value for predicting pazopanib efficacy. Methods: Tumour tissues from patients with advanced STS who went on to receive pazopanib were assessed for PD-L1 expression. Immunohistochemistry was performed using an anti-PD-L1 antibody, and the PD-L1 tumour proportion score (TPS) was calculated as the percentage of at least 100 viable cells with positive expression, defined as TPS ≥ 1%. Results: Among the 67 patients, 8 (11.9%) achieved partial response and a median progression-free survival (PFS) of 4.8 months (95% CI 3.8-5.7). PD-L1 expression in tumour cells was detected in 13 (19.4%) cases and the TPS scores ranged from 1 to 100%, as follows: 0 (n = 54, 80.6%), 1-9% (n = 3, 4.5%), 10-49% (n = 9, 13.4%), and ≥ 50% (n = 1, 1.5%). PD-L1 positive tumours exhibited a poorer response to pazopanib treatment than the PD-L1 negative tumours (0% vs 14.8%, P = 0.07). PD-L1-positive tumours had significantly shorter PFS than the PD-L1-negative tumours (median PFS 2.8 vs 5.1 months, P = 0.003), and PD-L1 positivity was an independent predictor of poor response to pazopanib treatment (HR 2.77, 95% CI; 1.45-5.56, P = 0.006). Conclusion: We identified that PD-L1 expression can help predict the clinical outcome of patients with advanced STS treated with pazopanib. Based on our study, stratification should be actively considered in order to identify patients who will benefit from pazopanib or further therapeutic strategies for future clinical trials.ope