• 대한두경부종양학회지
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• 제1권1호
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• pp.87-94
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• 1985

A total of eighty five cases with supraglottic carcinoma treated by radical radiotherapy in Yonsei Cancer Center between Jan. 1974 and Dec. 1980, was observed through retrospective analysis. This study is concerned wi th patients selection for irradiation alone or combined treatment with surgery. Emphasis is directed to the analysis of effectiveness of radical radiotherapy instead of partial laryngectomy in T-1, T-2 and early T-3 lesion. A satisfactory control of laryngeal disease and preservation of a normal voice ranging from 100% for $T_1N_0$ lesions, 61.1% for $T_2N_0$ to 50% for $T_3N_0$. But 47.1% of cases with node metastasis on admission had poor results to irradiation suggesting of necessicity of combined treatment. 5 year recurrence-free survivals was 43.3% in all cases with supraglottic carcinoma treated by irradiation alone, although it was 87.5% in T-1 and 51.8% in T-2.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.418-426
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• 2022

Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1⁺ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8⁺ T cells having CD8⁺CD44⁺CD62L^low phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.

• Archives of Pharmacal Research
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• 제27권6호
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• pp.633-639
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• 2004

The expression of therapeutic transgenes in recombinant adenoviral vectors is a major cause of toxicity in dividing cancer cells as well as non dividing normal cells. To solve the problem of toxicity to normal cells, we have reported on a recombinant adenoviral vector system （AdLP-） in which the expression of the transgene is directed by the tumor-specific L-plastin promoter （LP） （Chung et al., 1999）. The object of this study was to generate a recombinant adenoviral vector system which would generate tumor cell specific expression of cytosine deaminase （CD） gene. We report the construction of a replication-incompetent adenoviral vector in which CD is driven by the L-plastin promoter （AdLPCD）. Infection of 293 cells by AdLPCD generated the functional CD protein as measured by HPLC analysis for the conversion of 5-Fluorocy-tosine （5-FC） to 5-Fluorouracil （5-FU）. HPLC analysis in conjunction with counting radioactivity for ［6-$^3$H］-5FC and ［6-$^3$H］-5FU demonstrated vector dose-dependent conversion of 5-FC to 5-FU in AdLPCD infected ovarian cancer cells. The results from present and previous studies（Peng et al., 2001； Akbulut et al., 2003） suggest that the use of the AdLPCD／5-FC system may be of value in the treatment of cancer including microscopic ovarian cancer in the peritoneal cavity.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2151-2159
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• 2015

Pancreatic neuroendocrine tumors (pNETs) are rare and heterogenous tumors and surgery to remove the primary tumor is the mainstay of treatment for resectable disease. However, curative surgery is often not feasible, because half of patients with pNET have metastases at the time of diagnosis. Palliative dubulking surgery and liver-directed therapies are appropriate options for these patients. Streptozocin-based regimens are standard, although temozolamide-based treatments are rapidly gaining wide clinical application. Somatostatin analogs are mainly indicated in hormonally active tumors to ameliorate symptoms. In addition, anti-tumoral activity has been proven in well-differentiated NETs. Recently, there has been tremendous progress in the molecular biology of pNETs; thereby, the efficacy of sunitinib and everolimus in the treatment of patients with metastatic pNETs has been proven by large placebo-controlled phase III trials. Currently, there are no definitively proven predictive biomarkers to evaluate response to medical therapies in patients with pNET. Therefore, further studies are needed to individualize and optimize their management. This article reviews systemic chemotherapy, targeted therapies, and anti-secretory treatments for the management of patients with unresectable or metastatic pNETs, summarized in the light of recent advances.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5375-5378
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• 2013

Background: This study was undertaken to evaluate the surgical outcomes of patients with stage IA2 cervical cancer treated with radical hysterectomy. Data for 58 patients who underwent modified radical hysterectomy or radical hysterectomy with pelvic lymphadenectomy between January 2003 and December 2012 at Chiang Mai University Hospital were retrospectively reviewed. The analysis included clinico-pathological risk factors (nodal metastasis, parametrial involvement), adjuvant treatment, 5-year disease-free survival and 5-year overall survival. All pathologic slides were reviewed by a gynecologic pathologist. Follow-up methods included at least cervical cytology and colposcopy with directed biopsy if indicated. Univariate analysis was performed to identify factors associated with median survival. At the median follow up time of 73 months, the 5-year disease-free survival and the 5-year overall survival were 97.4% and 97.4%, respectively. Two (3.4%) patients had pelvic lymph node metastases. In a univariate analysis, there was no statistically significant association between survival and prognostic factors such as age, histological cell type, lymph-vascular space invasion, vaginal margin status and lymph node status. Surgical and survival outcomes of women with stage IA2 cervical cancer are excellent. No parametrial involvement was detected in our study. Patients with stage IA2 cervical cancer may be treated with simple or less radical hysterectomy with pelvic lymphadenectomy.

• 약학회지
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• 제49권1호
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• pp.38-43
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• 2005

The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment. This resistant phenotype of cancer cell frequently reveals a broad spectrum to structurally and/or functionally unrelated anticancer drugs, termed multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), a transmembrane drug efflux pump, is a major mechanism of MDR. Accordingly, considerable effort has been directed towards to development of compounds that inhibit P-gp, reverse the MDR phenotype and sensitize cancer cells to conventional chemotherapy without undesired toxicological effects. In an effort to search for novel MDR reversal agent, we tested the cytotoxicity of paclitaxel, a well-known substrate of P-gp, against P-gp-expressing HCT15 and HCT15/CL02 human colorectal cancer cells in the presence or absence of benzotriazepin analogues, as well as against P-gp-negative A549 human non-small cell lung and SK-OV-3 human ovarian cancer cells in vitro. Among the compounds tested, the agents that have phenyl amide moiety at 3 position remarkably increased the cytotoxicity of paclitaxel against P-gp-expressing cancer cells, but not against P-gp-negative cancer cells. BTZ-15 and BTZ-16 at $4\;{\mu}M$ revealed similar MDR reversal activity to $10\;{\mu}M$ verapamil, a well-known MDR reversal agent.

• The Korean journal of internal medicine
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• 제39권2호
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• pp.306-317
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• 2024

Background/Aims: To determine whether metformin, which is considered a host-directed therapy for tuberculosis (TB), is effective in improving the prognosis of patients with TB and diabetes mellitus (DM), who have higher mortality than those without DM. Methods: This cohort study included patients who were registered as having TB in the National Tuberculosis Surveillance System. The medical and death records of matched patients were obtained from the National Health Information Database and Statistics Korea, respectively, and data from 2011 to 2017 were collected retrospectively. We classified patients according to metformin use among participants who used diabetes drugs for more than 28 days. The primary outcome was all-cause mortality during TB treatment. Double propensity score adjustment was applied to reduce the effects of confounding and multivariable Cox proportional hazard models were used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (CI). Results: The all-cause mortality rate during TB treatment was lower (9.5% vs. 12.4%, p < 0.01) in the metformin user group. The hazard of death due to all causes after double propensity score adjustment was also lower in the metformin user group (aHR 0.76, 95% CI 0.67-0.86, p < 0.01). There was no significant difference in mortality between metformin users and non-users for TB-related deaths (p = 0.22); however, there was a significant difference in the non-TB-related deaths (p < 0.01). Conclusions: Metformin use in patients with TB-DM co-prevalence is associated with reduced all-cause mortality, suggesting the potential for metformin adjuvant therapy in these patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3191-3196
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• 2013

Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

• 대한두경부종양학회지
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• 제38권2호
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• pp.7-13
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• 2022

Human papillomavirus (HPV) is a causative agent for a subset of oropharyngeal cancer (OPC). The current standard of care (SOC) for locally advanced OPC is 70 Gy definitive radiotherapy (RT) concurrent with cisplatin, which entails significant proportions of acute and late grade 3 or higher toxicities. Accordingly, discovery of favorable prognosis of HPV-related OPC has led to enthusiasm to attenuate subspecialties therapy in multidisciplinary treatment. Diverse deintensification strategies were investigated in multiple phase 2 trials with an assumption that attenuated treatments result in comparable oncologic outcome and less toxicities compared with SOC. Several trials on chemotherapy deintensification revealed that concomitant administration of cisplatin is not to be omitted or substituted for cetuximab without compromising progression-free survival or local control. A transoral robotic surgery (TORS) is investigated as alternative local treatment, but TORS plus SOC or mild deintensified adjuvant RT showed similar toxicities and inferior oncologic outcomes compared with SOC definitive RT or moderately deintensified RT. However, it has been reported that TORS plus deintensified 30-36 Gy adjuvant RT results in excellent outcome and less late toxicity compared with SOC adjuvant RT. Several phase 2 trials reported apparently equivalent progression-free survival and local control and similar adverse effects with moderately deintensified 60 Gy RT compared with SOC 70 Gy RT. Further dose reduction below 60 Gy has been investigated using biology-directed approaches, which use response to induction chemotherapy or metabolic images to triage HPV-positive OPC for deintensified RT. In summary, these trials provide valuable insights for future directions. Available evidence consistently showed that moderately deintensified RT is effective and safe for HPV-positive OPC in both definitive and adjuvant settings. Concurrent cisplatin remains an essential component without which progression-free survival is significantly compromised for advanced HPV-positive OPC. A simple incorporation of TORS to SOC may be detrimental for oncologic outcome without anticipated toxicity reduction. Given the lack of level 1 evidence, it is prudent to curb an unjustified deviation from the current SOC and limit any deintensified strategies to clinical trials and adhere to the current SOC.

• 한국의학물리학회지:의학물리
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• 제15권3호
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• pp.149-155
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• 2004

목적: 전립선암의 세기조절 방사선 치료 시, 조직의 밀도보정 여부가 선량분포에 끼치는 영향을 연구한다. 재료 및 방법: 5명의 전립선 암 환자에 대하여 6 MV와 10 MV의 광자선에 대하여 각각 치료계획을 수립하였다. 각각 의 계획에서 7개의 조사선이 설정되었고, 선량계산 시에는 체조직의 밀도의 불균일성을 무시하였다. 선량 처방점인 회전중심점에서의 흡수선량과 계획표적용적(PTV)의 최대선량, 최소선량, 평균선량과 처방점선량의 95% 이상의 받는 부피(V>$_{p95%}$) 등을 측정하였다. 직장과 방광 내에서의 최대선량, 최소선량, 최방선량의 50%, 75%, 90% 이상을 받는 부피를 측정하였다. 동일한 조건에서 조직의 밀도 불균일성을 포함하여 선량분포를 재계산하고, 측정한 모든 물리량을 재 측정하였다. 결과: 밀도보정을 함으로써, 처방점에서의 흡수 선량은 6 MV에서 평균 4.9% 10 MV에서는 평균 4% 감소하였다. V>$_{p95%}$는 6 MV와 10 MV에서 각각 0.8%와 0.9% 감소하였다. PTV의 평균 흡수 선량은 6 MV와 10 MV에서 각각 4.2% 와 3.4% 감소하였다. 직장과 방광에서의 흡수선량은 약 l～2%의 차이를 보였다 결론: 전립선암의 세기변조 방사선치료시에 밀도보정을 무시하는 것은 표적에는 고려할 만한 선량의 차이를 유발하며, 주위의 위험장기에 미치는 영향은 미미하다.