• Title/Summary/Keyword: 5-Fluorouracil (5-Fu)

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Fabrication of Composite Drug Delivery System Using Nano Composite Deposition System and in vivo Characterization

  • Chu, Won-Shik;Jeong, Suk-Yong;Pandey, Jitendra Kumar;Ahn, Sung-Hoon;Lee, Jae-Hoon;Chi, Sang-Cheol
    • International Journal of Precision Engineering and Manufacturing
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    • v.9 no.2
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    • pp.81-83
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    • 2008
  • The Rapid Prototyping (RP) technology has advanced in many application areas. In this research, two different types, cylinder and scaffold, of implantable Drug Delivery System (DDS) were fabricated using Nano Composite Deposition System (NCDS), one of the RP systems. The anti-cancer drug (5-fluorouracil, 5-FU), biodegradable polymer (PLGA(85: 15)), and bio ceramic (Hydroxyapatite, HA) were used to form drug-polymer composite material. Both types of DDS were evaluated in vivo environment for two weeks. For evaluation, the cumulative drug release and shape stability were measured. Test results showed that the scaffold DDS provide higher cumulative drug release and has better stability than cylinder DDS.

The clinical outcomes of second-line chemotherapy in patients with advanced pancreatic cancer: a retrospective study

  • Jung, Hyun yeb;Lee, Eun Mi
    • Journal of Yeungnam Medical Science
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    • v.39 no.2
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    • pp.124-132
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    • 2022
  • Background: Despite recent advances in first-line chemotherapy for advanced pancreatic cancer, standard treatment after the failure of initial chemotherapy has not been established. Hence, we aimed to retrospectively analyze the clinical characteristics and outcomes of second-line chemotherapy in patients with advanced pancreatic cancer. Methods: We reviewed the clinical data of patients with advanced pancreatic cancer who underwent palliative chemotherapy at Kosin University Gospel Hospital between January 2013 and October 2020. Results: Among 366 patients with advanced pancreatic cancer who had received palliative chemotherapy, 104 (28.4%) underwent at least one cycle of second-line chemotherapy. The median age of the patients at the time of initiating second-line treatment was 62 years (interquartile range, 57-62 years), and 58.7% (61 patients) of them were male. The common second-line chemotherapy regimens were 5-fluorouracil (FU) plus leucovorin, irinotecan, and oxaliplatin (33 patients, 31.7%); gemcitabine/nab-paclitaxel (29, 27.9%), gemcitabine±erlotinib (13, 12.5%); and oxaliplatin and 5-FU/leucovorin (12, 11.5%). The median overall survival (OS) and progression-free survival were 6.4 months (95% confidence interval [CI], 4.5-8.6 months) and 4.5 months (95% CI, 2.7-6.3 months), respectively. In a multivariate analysis, poor performance status (PS) (hazard ratio [HR], 2.247; p=0.021), metastatic disease (HR, 2.745; p=0.011), and elevated carcinoembryonic antigen (CEA) levels (HR, 1.939; p=0.030) at the beginning of second-line chemotherapy were associated with poor OS. Conclusion: The survival outcome of second-line chemotherapy for advanced pancreatic cancer remains poor. However, PS, disease extent (locally advanced or metastatic), and CEA level may help determine patients who could benefit from second-line treatment.

Low-Dose Docetaxel/Cisplatin - Leucovorin and 46 Hour Infusional Fluorouracil in Metastatic Gastric Carcinoma

  • Alici, Suleyman;Buyukberber, Suleyman;Alkis, Necati;Benekli, Mustafa;Ozkan, Metin;Bilici, Ahmet;Demirci, Umut;Karaca, Halit;Arpaci, Erkan;Gumus, Mahmut;Altunbas, Mustafa;Dane, Faysal;Turk, H. Mehmet;Anatolian Society of Medical Oncology
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.423-427
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    • 2013
  • Background: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but with high rates of hematologic toxicity in metastatic gastric cancer cases. To reduce toxicity while maintaining the efficacy of DCF, we investigated low dose docetaxel (D), cispatin (C) - leucovorin and fluorouracil (De Gramont regimen). Patient and methods: Chemotherapy-naïve patients with metastatic gastric cancer (MGC) received D 60 mg/$m^2$ on day 1 and cisplatin 30 mg/$m^2$ on day 1-2 and the De Gramont regimen (Folinic acid 400 mg/m2 on day 1 and 5-FU 2400 mg/$m^2$/46h continuous infusion) every 3 weeks. The primary endpoint was response rate. Results: One hundred twenty patients with a median age of 52.5 years (range, 32-78) received a median of 6 cycles (range, 2-12 cycles). Of the 120 evaluable patients, 4 showed complete remission and 36 achieved a partial response. The overall response rate was 56.6%. Twenty eight patients (23.3%) showed stable disease and 52 (43.3%) progression. The median time to progression was 7 months (95%CI 6-7.9). The median overall survival was 15 months (95%CI 13.7-16.2). The most frequent hematological toxicity was leucopenia, which occurred at grade 3/4 intensity in 24 patients (20%). Conclusions: Low-dose DC-De Gramont regimen is active in MGC with a tolerable toxicity profile.

Cytotoxic Effects of an Oncolytic Adenoviral Vector AdLPCDIRESE1A in Hepatocellular Carcinoma Cells (암세포 용해성 AdLPCDIRESE1A 벡터의 간암 세포독성효과)

  • Chung, In-Jae
    • YAKHAK HOEJI
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    • v.55 no.1
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    • pp.75-79
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    • 2011
  • The replication competent adenoviral vector (AV), AdLPCDIRESE1A was generated and reported previously to have cytotoxic effects in some cell lines. In AdLPCDIRESE1A, the expression of cytosine deaminse (CD) and E1A genes are under the control of tumor-specific L-plastin promoter. CD enzyme can deaminate the nontoxic prodrug 5-fluorocytosine (5-FC) to the toxic 5-fluorouracil (5-FU). E1A gene is essential for viral replication. Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. Thus, we have conducted in vitro preclinical study to evaluate effectiveness of AdLPCDIRESE1A on HCC. The efficacy of cytotoxicity was measured by generation of cytopathic effect (CPE) and cell counting. We infected HepG2 cells with various MOI of vector alone or concurrent with 5-FC. Exposure of cells to AdLPCDIRESE1A generated a significant cytotoxic effect as compared to the control. Almost 83% of the cell had manifested the characteristic cytotoxic effect on day 9 after infection of cells with 10 MOI of vector. We also observed the additive cytotoxic effects when AdLPCDIRESE1A vector had been coadministrated with 5-FC. The results suggest that the use of AdLPCDIRESE1A/5FC may be value in treatment of liver cancer. Further animal studies are needed for clinical trial.

Chemotherapy for Head and Neck Squamous Cell Carcinoma (두경부 상피세포암의 화학요법)

  • Roh Jae-Kyung
    • Korean Journal of Head & Neck Oncology
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    • v.6 no.1
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    • pp.11-23
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    • 1990
  • Systemic chemotherapy is usually regarded as the standard treatment for palliation in patients with recurrent or metastatic cancer who have failed the definite local treatment with surgery and/or radiotherapy. Recently, with the introduction of more active chemotherapeutic agents and combinations, systemic chemotherapy is being increasingly used before or after local therapy in patients with previously untreated locally advanced head and neck cancer. The most active agents for the head and neck caner are methotrexate, 5-fluorouracil (5-FU), cisplatin and bleomycin. The overall response rates to each of these four drugs are 15-30% expecially when used as first line therapy. But most of these responses are partial with a mean duration of 3-5 months. Various combinations with methotrexate, 5-FU, cisplatin, and bleomycin have been tried with overall response rates of 50-90%, and 10-20% of complete responses. The introduction of chemotherapy prior to local therapy, induction chemotherapy, has been investigated with improved survivals in patients with complete response, especially pathologic, though improvement in overall survival has not been proved yet after the induction chemotherapy. Other therapeutic modalities, such as 'Sandwich' chemotherapy between surgery and radiotherapy, concomittent chemo-radiotherapy and post local treatment adjuvant chemotherapy have been pursued with some hopeful results but these trials should be compared with prospective randomized Phase III trials. To increase the response rates and enhance the survival, important work still remains; 1. Identification of better prognostic factors, 2. Improvement in staging, 3. Development of more active and safter chemotherapeutic agents, 4. Identification of the proper sequence for the addition of chemotherapy to multimodality treatment, and 5. Testing the value of such chemotherapy in locally advanced cancer patients.

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Astudy on the Anticancer Activies of Lipid Soluble Ginseng Extract and Ginseng Sapongin DErivatives Against Some Cancer Cells (인삼의 지용성 성분과 사포닌 유도체의 항암작용 연구)

  • 항우익;오수경
    • Journal of Ginseng Research
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    • v.8 no.2
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    • pp.153-166
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    • 1984
  • The anticancer activities of petroleum ether extract of Panax ginseng root(crude GX) and its partially purified fraction from silicic acid column chromatography (7:3 GX) were studied with Sarcoma 180(S-180) or Walker carcinosarcoma 256 (Walker 256) in vivo and with L1210 leukemic lympocyte in vitro. Potential cytotoxic activities of the crude GX and against L1210 cells were compared with those of 5-Fluorouracil (5-FU) and saponin derivatives (Panax-diol, Panax-triol, Diol saponin, Triol saponin) in vitro. In order to observe the physiological effects of the crude GX and 7:3 GX on the animals with cancer, hemoglobin(Hb), red blood cell(R.B.C) and white blood cell after treatment with each GX in comparison with corresponding control groups, respectively. The anticancer effects of the crude GX and 7:3 GX were estimated by measuring the survival time of S-180 bearing mice after treatment with them. The experimental results obtained are summarized as follows; 1. The one unit of cytotoxic activity against L1210 cells was equivalent to 2.54$\mu\textrm{g}$ and 0.88$\mu\textrm{g}$of the crude GX and 7:3 GX per ml of culture medium, respectively. 2. The cytotoxic activities of Panax-diol, Panax=triol, Diol saponin and triol saponin against L1210 cells were not detected. 3. The anticancer activities of 5-FU against L1210, S-180 and Walker 256 were very effective in vivo and vitro tests. 4. The significantly increased W.B.C values of mice after inoculation with S-180 cells were reduced to normal range by the crude GX treatment. 5. The significantly decreased Hb values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude GX. 6. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7:3 GX treatment compared with their control group.

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Clinical Observation on Recombinant Human Endostatin Combined with Chemotherapy for Advanced Gastrointestinal Cancer

  • Gao, Shao-Rong;Li, Lu-Ming;Xia, Hai-Ping;Wang, Guang-Ming;Xu, Hong-Yan;Wang, Ai-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.4037-4040
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    • 2015
  • Objective: To explore the clinical efficacy and toxic and side effects of recombinant human endostatin (rhendostatin/endostar) combined with chemotherapy in the treatment of advanced gastric cancer. Materials and Methods: A total of 70 patients with advanced gastrointestinal adenocarcioma confirmed by histopathology and/or cytological examination were divided into group A (37 patients) and group B (33 patients). Patients in group A were given intravenous drip of 15 mg endostar added into 500 mL normal saline, once every other day until the cessation of chemotherapy or patients' maximal tolerance to chemotherapy. Patients in group B received chemotherapy alone. Two groups selected the same chemotherapy regimens. FOLFIRI scheme: 90-min intravenous drip of $180mg/m^2$ irinotecan, intravenous drip of $200mg/m^2$ calcium folinate (CF) and $400mg/m^2$ 5-fluorouracil (5-Fu) on d1, and continuous intravenous pumping of 2 $400mg/m^2$ 5-Fu for 46 h. FOLFOX4 scheme: intravenous injection of $85mg/m^2$ oxaliplatin (L-OHP), $200mg/m^2$ calcium folinate (CF) and $400mg/m^2$ 5-FU on d1 for 2 h, and then continuous intravenous pumping of 2 $400mg/m^2$ 5-Fu for 46 h. XELOX scheme: oral administration of 1 $500mg/m^2$ xeloda (or tegafur 50~60 mg) in twice during d1~14 and intravenous drip of $135mg/m^2$ L-OHP on d1 for 2 h. The modified FOLFOX scheme: intravenous injection of $135mg/m^2$ L-OHP on d1 for 2 h, $200mg/m^2$ CF and 1.0 g tegafur during d1~5. Whereas, control Group B received chemotherapy regimens which were same as Group A, but no addition of endostar. Before chemotherapy, patients were given intravenous injection of 8 mg ondansetron, intramuscular injection of 10 mg metoclopramide and 20 mg diphenhydramine for prevention of vomiting, protection of liver and stomach as well as symptomatic supportive treatment. One cycle was 21 d, 4~6 cycles in total. The efficacy was evaluated every 2 cycles. Results: 32 patients in Group A could be evaluated, and the response rate (RR) and disease control rate (DCR) were 59.38% and 78.13%, respectively. 31 patients in Groups could be evaluated, and the RR and DCR were 32.26% and 54.84%, respectively. The differences between 2 groups were significant. The toxic effects include myelosuppression, gastrointestinal reaction, fatigue, cardiotoxicity and peripheral neurotoxicity. Conclusions: Preliminary observations show that endostar (once every other day) combined with chemotherapy is effective in the treatment of advanced gastrointestinal cancer, with low toxic effects, good tolerance, deserving further study.

Quality of Life in Colorectal Cancer Patients at Home 5-Fluorouracil Chemotherapy with Disposable Elastomeric Infusion Pumps (일회용 약물주입기로 가정에서 항암치료 중인 대장암 환자의 삶의 질)

  • Lee, Chung Eun;Kim, Na Young;Park, Me Hee;Lee, Yoon Jung;Kim, Jin Ra;Baek, Min Ju;Kim, Hyo Jin;Byun, Eun Sung;Kil, Yun Kyung;Kim, Heejung
    • Journal of Korean Clinical Nursing Research
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    • v.28 no.1
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    • pp.76-87
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    • 2022
  • Purpose: The purpose of this study was to examine the psychological distress related to quality of life (QoL) of patients with colorectal cancer receiving 5-fluorouracil (5-FU) chemotherapy at home with disposable Elastomeric infusion pumps. Methods: In this study, 179 colorectal outpatients were recruited between September 2019 and January 2021. National Cancer Center Psychological Symptom Inventory scores, general self-efficacy, and the EORTC QLQ-C30 scores were measured. Data were analyzed using Independent t-test, One-way ANOVA with Bonferroni post hoc analysis, and hierarchical multiple linear regression with the SPSS/WIN 26.0 programs. Results: The overall prevalence of psychological distress was 52.0% in colorectal patients. In multiple regression, psychological distress (β=-.20, p=.005), appetite loss (β=-.20, p=.001), chemotherapy cycles (β= .19, p=.002), fatigue (β=-.16, p=.035), physical functioning (β=-.16, p=.024), and emotional functioning (β=-.15, p=.025) were significant factors of QoL, and the final model explained 45.0% of the total variance of QoL. Conclusion: Supporting patients toward decreased psychological distress and increased physical and emotional functioning, especially in the first or second cycle of chemotherapy, could be used to improve their QoL. To consider the thresholds for clinical importance, it is necessary to increase the interpretation of psychological distress in clinical practice and further research.

Cytotoxicity of Cytosine Deaminase (CD) Adenoviral Vectors(AV) with a Promoter (L-plastin) for Epithelial Cancer Cells.

  • Chung, Injae;Jung, Kihwa;Deisseroth, Albert B.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.80-80
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    • 1997
  • The object of this study was to develop a gene therapy strategy for ovarian cancer. We have previously shown that AV with a L-plastin (LP) promoter infects breast and ovarian cancer cells and expressed ${\beta}$-galactosidase cDNA in preference to normal fibroblast cells and hematopoietic cells. We now report on the cytotoxicity of Ad.LP.CD, an AV carrying a CD cDNA which converts the pro-drug, 5-Fluorocytosine (5-FC) into the toxic drug 5-Fluorouracil (5-FU). Infection of Ad.LP.CD into either 293 cells or ovarian cancer cells generated the functional CD as measured by HPLC analysis. Using a ratio of AV to OVCAR3 cell of 100 and a 5-FC concentration of 100 ${\mu}$M, we achieve an over 95 % of cell growth inhibition. We are using flow cytometry analysis for ${\beta}$ -galactosidase and ovarian cancer associated folate receptor to screen primary ascites samples for infectivity after infection with an adenoviral vector, i.e., Ad.LP.LacZ. This vector system may be of value in the treatment of microscopic disease of ovarian cancer in the peritoneal cavity.

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Association between Chemotherapy-Response Assays and Subsets of Tumor-Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study

  • Lee, Jee Youn;Son, Taeil;Cheong, Jae-Ho;Hyung, Woo Jin;Noh, Sung Hoon;Kim, Choong-Bai;Park, Chung-Gyu;Kim, Hyoung-Il
    • Journal of Gastric Cancer
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    • v.15 no.4
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    • pp.223-230
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    • 2015
  • Purpose: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. Materials and Methods: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. Results: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. Conclusions: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.