• Korean Journal of Head & Neck Oncology
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• v.1 no.1
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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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• v.30 no.5
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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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• v.27 no.6
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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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• v.16 no.6
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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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• v.14 no.9
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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.

• YAKHAK HOEJI
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• v.49 no.1
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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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.

• Korean Journal of Head & Neck Oncology
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• v.38 no.2
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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.

• Progress in Medical Physics
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• v.15 no.3
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• pp.149-155
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• 2004

Purpose: To investigate the effects of tissue inhomogeneity corrections on the dose delivered to prostate cancer patients treated with Intensity-Modulated Radiation Therapy (IMRT). Methods and Materials: For five prostate cancer patients, IMRT treatment plans were generated using 6 MV or 10 MV X-rays. In each plan, seven equally spaced ports of photon beams were directed to the isocenter, neglecting the tissue heterogeneity in the body. The dose at the isocenter, mean dose, maximum dose, minimum dose and volume that received more than 95% of the isocenter dose in the planning target volume ( $V_{p>95%}$) were measured. The maximum doses to the rectum and the bladder, and the volumes that received more than 50, 75 and 90% of the prescribed dose were measured. Treatment plans were then recomputed using tissue inhomogeneity correction maintaining the intensity profiles and monitor units of each port. The prescription point dose and other dosimetric parameters were remeasured. Results: The inhomogeneity correction reduced the prescription point dose by an average 4.9 and 4.0% with 6 and 10 MV X-rays, respectively. The average reductions of the $V_{p>95%}$ were 0.8 and 0.9% with the 6 and 10 MV X-rays, respectively. The mean doses in the PTV were reduced by an average of 4.2 and 3.4% with the 6 and 10 MV X-rays, respectively. The irradiated volume parameters in the rectum and bladder were less decreased; less than 2.1 % (1.2%) of the reduction in the rectum (bladder). The average reductions in the mean dose were 1.0 and 0.5% in the rectum and bladder, respectively. Conclusions: Neglect of tissue inhomogeneity in the IMRT treatment of prostate cancer gives rise to a notable overestimation of the dose delivered to the target, whereas the impact of tissue inhomogeneity correction to the surrounding critical organs is less significant.

• Molecules and Cells
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• v.41 no.11
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• pp.933-942
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• 2018

Traditionally, small-molecule or antibody-based therapies against human diseases have been designed to inhibit the enzymatic activity or compete for the ligand binding sites of pathological target proteins. Despite its demonstrated effectiveness, such as in cancer treatment, this approach is often limited by recurring drug resistance. More importantly, not all molecular targets are enzymes or receptors with druggable 'hot spots' that can be directly occupied by active site-directed inhibitors. Recently, a promising new paradigm has been created, in which small-molecule chemicals harness the naturally occurring protein quality control machinery of the ubiquitin-proteasome system to specifically eradicate disease-causing proteins in cells. Such 'chemically induced protein degradation' may provide unprecedented opportunities for targeting proteins that are inherently undruggable, such as structural scaffolds and other non-enzymatic molecules, for therapeutic purposes. This review focuses on surveying recent progress in developing E3-guided proteolysis-targeting chimeras (PROTACs) and small-molecule chemical modulators of deubiquitinating enzymes upstream of or on the proteasome.