• 제목/요약/키워드: tumor response

검색결과 1,398건 처리시간 0.026초

Identification of CM1 as a Pathogenic Factor in Inflammatory Diseases and Cancer

  • Bae, Se-Yeon;Kim, Hyem-In;Yu, Yeon-Sil;Lee, Na-Eun;Kong, Joo-Myoung;Kim, Hang-Rae;Hwang, Young-Il;Song, Yeong-Wook;Kang, Jae-Seung;Lee, Wang-Jae
    • IMMUNE NETWORK
    • /
    • 제11권3호
    • /
    • pp.175-181
    • /
    • 2011
  • Background: CM1 (centrocyte/-blast marker 1) was defined by a mAb against concavabalin-A (ConA) activated PBMC. It is expressed in germinal center of human tonsil and on the surface of activated PBMC as well as cancer cells. Recently, increased productions of pro-inflammatory mediators were detected from activated PBMC by CM1 ligation. Methods: However, there is a limitation to explain the exact role of CM1 on inflammation and its related mechanisms, since the identity of CM1 is still not clarified. In our previous study, we have already confirmed that soluble form of CM1 was produced by Raji. Therefore, we performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture supernatant using anti-CM1 mAbs. Results: As a result, we found that CM1 is identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results by silencing ENO1 using siRNA. It was also confirmed through competition assay between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells with anti-CM1 mAbs induces the extensive production of prostaglandin $E_2(PGE_2)$. In addition, the increased activity of matrix metalloproteinase (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation. Conclusion: CM1 is identical to ENO1 and it might be an important role in the regulation of inflammatory responses.

향장기성 두경부 편평세포암종의 미세잔존암 모델에서 GM-CSF 유전자를 이입시킨 제한복제성 헤르페스바이러스 벡터를 이용한 종양백신의 유전자 치료 (Gene Therapy Using GM-CSF Gene Transferred by a Defective Infectious Single-cycle Herpes Virus in Micro-residual Organotropic Head and Neck Squamous Cell Cancer Model)

  • 김세헌;최은창;김한수;장정현;김지훈;김광문
    • 대한두경부종양학회지
    • /
    • 제19권1호
    • /
    • pp.25-33
    • /
    • 2003
  • Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.

암줄기세포와 종양 미세환경에 대한 고찰 (Cancer Stem Cells and the Tumor Microenvironment)

  • 우수연;최희선;유강희;김준서;윤열희;이승연;최재혁;김경호;이강준;황승현;이동준
    • 생명과학회지
    • /
    • 제34권6호
    • /
    • pp.418-425
    • /
    • 2024
  • 고형암은 여러 세포 유형의 이질적인 집단으로 구성되며, 암줄기세포는 자가 재생과 분화의 특성을 가지고 있다. 암줄기세포에서는 자가재생을 조절하는 줄기세포 신호전달체계가 과도하게 활성화되어 있어 암줄기세포는 암세포의 증식과 암 진행에 중요하다. 암줄기세포의 정의는 급성골수성백혈병에 의해 처음 제안되었으며, 다양한 연구를 통해 세포 표면 표지 발현에 따라 암 줄기세포를 분류할 수 있게 되었다. 또한, 암줄기세포는 종양 미세환경에서 잠재력을 보존하고 있고, 다양한 종양 미세환경 세포 유형은 정지 상태의 암줄기 세포를 유지하고 암 성장의 조절자 역할을 한다. 현재 사용되는 암 치료 방법은 증식성 세포를 표적으로 하기 때문에 치료에, 저항성을 가지는 휴지기 상태의 암 줄기세포는 재발이나 전이의 위험을 증가시키며, 종양 미세환경의 다양한 신호전달체계는 혈관계와 세포 외 기질을 리모델링함으로써 종양 지지 환경으로의 변화를 유도한다. 따라서, 암을 효과적으로 치료하려면 암줄기세포와 종양 미세환경을 표적 치료해야 하며, 종양 미세환경이 어떻게 면역 반응의 재프로그램을 유도하여 암의 성장, 면역 저항성 및 전이를 촉진하는지 이해하는 것이 중요하다. 따라서 본 총설을 통해 종양 미세환경에서 면역억제를 강화할 수 있는 세포 및 분자 메커니즘에 대한 현재 및 새로운 개념을 요약하고자 한다.

Glutathione S-transferase P1 and DNA Polymorphisms with the Response to Chemotherapy and the Prognosis of Bone Tumor

  • Yang, Li-Min;Li, Xiu-Hua;Bao, Cui-Fen
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권11호
    • /
    • pp.5883-5886
    • /
    • 2012
  • Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the response of GSTP1, ERCC1 and ERCC2 to chemotherapy among osteosarcoma patients, and the role of these genes on the prognosis of osteosarcoma. 187 patients with osteosarcoma were administered with methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine treatment. GSTP1, ERCC1 and ERCC2 polymorphism was genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.25). Individuals with ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated test of GSTP1 and ERCC2 Lys751Gln polymorphisms might be a candidate pharmacogenomic factors to be explored in the future to identify the osteosarcoma patients who might benefit from chemotherapy.

Clinical Application of the Adenosine Triphosphate-based Response Assay in Intravesical Chemotherapy for Superficial Bladder Cancer

  • Ge, Wen-Qing;Pu, Jin-Xian;Zheng, Shi-Ying
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권2호
    • /
    • pp.689-692
    • /
    • 2012
  • Objective: To investigate correlations between adenosine triphosphate chemotherapy response assay (ATP-CRA) and clinical outcomes after ATP-CRA-based chemotherapy for drug selection in patients receiving intravesical chemotherapy to prevent recurrence of superficial bladder cancer after surgery. Methods: The chemosensitivities of 12 anticancer drugs were evaluated, including 5-Fu ADM, and EPI, using ATP-CRA and primary tumor cell culture in 54 patients. In addition, a further 58 patients were treated according to clinical experience. Differences in post-chemotherapeutical effects between drug sensitivity assay and experience groups were compared. Results: The evaluable rate of the test was 96.3%, the clinical effective rate was 80.8%, the sensitivity rate was 97.6% (41/42), the specificity was 20%, the total predicting accuracy was 74.3%, the positive predictive value was 83.7% (41/49), the negative predictive value was 66.7% (2/3); in the drug sensitivity test group, the clinical effective rate was 80.8%, the experience group response rate was 63.8%, with a significant difference in clinical effects between the ATP-based sensitivity and experience groups (${\chi}^2$=7.0153, P<0.01). Conclusion: ATP-CRA is a stable, accurate and potentially practical chemosensitivity test providing a predictor of chemotherapeutic response in patients with superficial bladder cancer.

한방치료와 화학·방사선요법을 병행하여 완전 관해된 진행성 위암 환자 1례 (A Case Report of Complete Response of Advanced Gastric Carcinoma Patient Treated with Korean Medicine Treatment in Conjunction with Chemoradiation Therapy)

  • 이재찬;윤호영;유화승;방선휘
    • 대한암한의학회지
    • /
    • 제19권1호
    • /
    • pp.25-32
    • /
    • 2014
  • Objectives : The purpose of this study is to report the effect of Korean Medicine Treatment (KMT) on the advanced gastric carcinoma (AGC) patient. Method : One advanced gastric carcinoma patient was treated by Korean Medicine Treatment composed of pharmacopuncture, acupuncture and herbal medicine. At the same time, he received chemotherapy (S-1 and Cisplatin) and radiotherapy. The effect of KMT was measured by scanning with Computed tomography (CT) and Esophagogastroduodenoscopy (EGD). Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee classification. Result : The tumor was disappeared after the treatment during 13 months (Complete Response (CR)). As treatment was performed, chemoradiation therapy induced complication was alleviated. Conclusion : This case provides us a possibility that Korean Medicine Treatment offers potential benefits for advanced gastric carcinoma patient.

Role of RUNX Family Transcription Factors in DNA Damage Response

  • Samarakkody, Ann Sanoji;Shin, Nah-Young;Cantor, Alan B.
    • Molecules and Cells
    • /
    • 제43권2호
    • /
    • pp.99-106
    • /
    • 2020
  • Cells are constantly exposed to endogenous and exogenous stresses that can result in DNA damage. In response, they have evolved complex pathways to maintain genomic integrity. RUNX family transcription factors (RUNX1, RUNX2, and RUNX3 in mammals) are master regulators of development and differentiation, and are frequently dysregulated in cancer. A growing body of research also implicates RUNX proteins as regulators of the DNA damage response, often acting in conjunction with the p53 and Fanconi anemia pathways. In this review, we discuss the functional role and mechanisms involved in RUNX factor mediated response to DNA damage and other cellular stresses. We highlight the impact of these new findings on our understanding of cancer predisposition associated with RUNX factor dysregulation and their implications for designing novel approaches to prevent cancer formation in affected individuals.

Oral propranolol therapy in 23 infants with infantile hemangioma

  • Kim, Jaeyoon;Hong, Jong Won;Roh, Tai Suk;Lee, Won Jai
    • Archives of Plastic Surgery
    • /
    • 제45권6호
    • /
    • pp.517-524
    • /
    • 2018
  • Background Infantile hemangioma (IH) is a common vascular tumor in pediatric patients, and is commonly treated with propranolol. We describe our experiences with dosage, response to treatment, and side effects in 23 IH patients treated with propranolol. Methods For this nonrandomized comparative cohort study, the authors enrolled 23 patients treated with propranolol. Photographs were taken before propranolol administration and at 3, 6, 9, and 12 months after treatment. Treatment responses were objectively analyzed with a computer program. Results There were three male and 20 female patients. Common tumor locations were the head and neck (13 cases, 56.5%), trunk (four cases, 17.4%), extremities (three cases, 13.0%), and combined locations (three cases, 13.0%). The response to propranolol was significantly lower in patients with two or more lesions than in patients with a single lesion in terms of both color fading (P<0.001) and size reduction (P<0.001). In male patients ($42.2{\pm}3.9$), the change in a-values, indicating coloration, was higher than in female patients ($19.8{\pm}13.8$) (P<0.001). In patients who started treatment before 6 months after birth, the size reduction was greater than in their counterparts (62.3%; range, 3.0%-93.0% vs. 15.8%; range, 1.0%-79.0%; P<0.001). Conclusions Propranolol is an efficacious treatment with a good safety profile. In patients with a single lesion, the response to treatment was better in terms of color fading and size reduction. Furthermore, male patients responded better to propranolol treatment in terms of color fading than female patients, and starting treatment before 6 months after birth was more advantageous for size reduction.

식도암의 방사선치료 성적 (The Result of Radiotherapy in Esophageal Cancer)

  • 박찬일;최은경;정웅기;방영주;김노경
    • Radiation Oncology Journal
    • /
    • 제6권2호
    • /
    • pp.227-233
    • /
    • 1988
  • 1979년 3월부터 1986년 8월까지 식도의 편평상피암으로 진단되어 서울대학교병원 치료방사선과에서 방사선치료를 받은 177명중 근치적 방사선 치료를 시행한 152명을 대상으로 후향성 분석을 시행하여 다음과 같은 결과를 얻었다. $80\%$이상의 환자에서 관해를 보였으며, 이중 완전관해는 $22\%$, 부분 관해는 $63\%$이었다. 전체 환자의 2년, 5년 생존율은 각각 $22.9\%,\; 13.3\%$이었으며 식도암의 위치, 크기, 병기 그리고 관해 정도에 따라 생존율에 차이가 있었다. 식도 촬영상 5cm 이하$(17\%)$ 또는 식도의 상부 1/3에 종양이 있는 경우$(25.6\%)$에 가장 좋은 5년 생존율을 보였다. 관해 정도에 따른 생존율은 완전관해를 보인 경우의 5년 생존율이 $34.3\%$인 반면 반응이 없던 경우는 $0\%$이었다

  • PDF

Involvement of miR-Let7A in inflammatory response and cell survival/apoptosis regulated by resveratrol in THP-1 macrophage

  • Song, Juhyun;Jun, Mira;Ahn, Mok-Ryeon;Kim, Oh Yoen
    • Nutrition Research and Practice
    • /
    • 제10권4호
    • /
    • pp.377-384
    • /
    • 2016
  • BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol ($25-200{\mu}M$) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.