• Journal of Yeungnam Medical Science
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• v.21 no.2
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• pp.198-206
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• 2004

Background: To evaluate the efficacy and safety of paclitaxel and cisplatin against advanced non-small cell lung cancer (NSCLC) as a second-line chemotherapy. Subjects and Methods: Twenty-five patients were enrolled. The patients received 200 $mg/m^2$ paclitaxel as a 3-hour intravenous infusion and 60 $mg/m^2$ cisplatin as 2D-minute intravenous infusion with vigorous hydration on day 1 every 28 days. The response was assessed every 2 cycles. Results: All 25 patients were assessed for their response and toxicity. Partial responses were observed in 5 patients. The overall response rate was 20%(95% confidence interval, 4%-36%) and the median response duration was 4.5(range, 2-11) months. The median time to progression was 3.3(range, 0-14) months. The median overall survival of all patients was 7.4(range, 1.3-39) months. The hematologic toxicities were minor and easily controlled. Conclusion: The combination chemotherapy of paclitaxel and cisplatin as a second-line treatment has a moderate efficacy with an acceptable toxicity in patients with advanced NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6275-6281
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• 2014

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received $2500IU/m^2$/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1661-1675
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• 2016

Objectives: Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)? Researchers differ on this question. Materials and Methods: Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. Results: A total of 38 RCTs involving 13,923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs 56.0%, P<0.001), acute phase (85.1% vs 79.6%, P<0.001), and delayed phase (71.4% vs 58.2%, P<0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, P<0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, P<0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs 45.9%, P<0.001; occurrence of vomiting: 22.6% vs 38.9%, P<0.001; usage of rescue drugs: 23.5% vs 34.1%, P<0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently detected in patients receiving NK1-RAs. Conclusions: NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.

• Journal of Gastric Cancer
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• v.18 no.4
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• pp.379-391
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• 2018

Purpose: Gastric cancer (GC) patients with peritoneal metastasis (PM) have poor prognosis. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with systemic chemotherapy is a novel treatment option for patients in stage IV of the disease. Materials and Methods: Between November 2015 and June 2018, prospective data collection was performed in 24 patients with GC and PM (median age, 57; range, 44-75 years). These patients underwent 46 PIPAC procedures with a median number of 2 interventions per patient (range, 1-6). A laparoscopic access was used and a combined therapy of cisplatin and doxorubicin aerosol was administered. Results: The median peritoneal carcinomatosis index before the 1st PIPAC was 14 (range, 2-36), and the median ascites volume in patients before the 1st PIPAC was 100 mL (range, 0-6 mL, 300 mL). Eleven patients, who received 2 or more PIPAC procedures, had decreased and stable volumes of ascites, while only 3 patients displayed increasing volume of ascites. The median overall survival was 121 days (range, 66-625 days) after the 1st PIPAC procedure, while 8 patients who received more than 3 PIPAC procedures had a median survival of 450 days (range, 206-481 days) (P=0.0376). Conclusions: Our data show that PIPAC is safe and well tolerated, and that the production of ascites can be controlled by PIPAC in GC patients. Patients, who received 2 or more PIPAC procedures, reported a stable overall quality of life. Further studies are required to document the significance of PIPAC as a palliative multimodal therapy.

• Journal of Digestive Cancer Research
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• v.1 no.2
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• pp.104-107
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• 2013

Gallbladder (GB) cancer is highly malignant neoplasm found in advanced stage and chemotherapy commonly plays a palliative role in GB cancer. We report a case of unresectable GB cancer treated with chemotherapy followed by extended cholecystectomy. Fifty-six-year-old male visited our hospital with weight loss and dyspnea on exertion. Computed tomography detected pulmonary embolism and diffuse GB wall thickening with para-aortic lymph node enlargement. The length of common channel was 23mm at magnetic resonance cholangiopancreatography which stands for anomalous union of the pancreaticobiliary duct. Anticoagulation was started for pulmonary embolism. GB wall mass was regarded as unresectable GB cancer with distant lymph node metastasis. Gemcitabine and cisplatin combination chemotherapy was carried out for 6 cycles. Primary tumor was stationary but multiple enlarged lymphnodes were almost completely disappeared. Extended cholecystectomy with hepaticojejunostomy was performed. Post-operative tumor stage was T3N1 (stage IIIB) and R0 resection was achieved. After operation he has no evidence of disease recurrence for 6 months.

• Korean Journal of Head & Neck Oncology
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• v.11 no.2
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• pp.145-152
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• 1995

A retrospective analysis was performed to ascertain the relationship between the treatment modalities and their treatment results. From July 1980 to June 1993, 115 patients with squamous cell carcinoma of the maxillary sinus were: treated at the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University. There were 88 men and 27 women with median age of 57 years. According to AJCC TNM system of 1992. eight patients of T2, 54 patients of T3 and 53 patients of T4 were available, respectively. Cervical lymph node metastases at diagnosis was observed in 11 patients. 87 patients were treated with radiotherapy and 28 patients were treated with combination of surgery and radiotherapy. The overall 5 year survival rate was 32 %, patients that were treated with radiotherapy alone had a 5 year survival rate 24.3 % and patients who were treated with combination of surgery and radiation therapy had a 5 year survival rate of 52.8 % (p<0.05). Combination of surgery and radiotherapy resulted in a better treatment modality for squamous cell carcinoma of the maxillary sinus. Improved radiotherapy technique and development of multimodality treatment are needed to improve the local control and the survival rate in patients with advanced maxillary sinus carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3907-3912
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• 2015

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.470-476
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• 2012

Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol ($100{\mu}M$) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells.

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.259-263
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• 2016

Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in a patient with NSCLC and bone metastasis. The Korean herbal medicine regimen included woohwanggeosa-dan, hwanggibujeong-dan and geonchilgyebok-jeong. The computed tomography (CT) findings showed that following combination treatment, the size of the tumor was markedly decreased without serious adverse events. Moreover, the Eastern Cooperative Oncology Group (ECOG) performance status was improved and cancer-related pain was decreased. These results suggest that a combination of Korean herbal medicines and gefitinib may be an effective therapeutic option for patients with advanced NSCLC and bone metastasis. Further studies are needed to examine the mechanism and the clinical efficacy of Korean herbal medicines against NSCLC.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.31-38
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• 2023

Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects.