• Title/Summary/Keyword: bleomycin

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Protection of ROS-induced cytotoxicity and DNA damage by the extract of Alpinia of ficinarum (양강추출물의 활성산소종 유도 세포독성과 DNA 손상에 대한 방어효과)

  • 이승철;신경승;허문영
    • Journal of Food Hygiene and Safety
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    • v.17 no.2
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    • pp.106-116
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    • 2002
  • The 70% ethanol extract of Alpinia officinarum and its major flavonoid, galangin showed strong antioxidative effect on the lipid peroxidation of ethyl linolate with Fenton's reagent and free radical scavenging effect to DPPH radical generation. However, they did not reveal any pro-oxidant effect on bleomycin-Fe(III) dependent DNA degradation. They also showed the protective effect against $H_2O$$_2$, KO$_2$ or UV-induced cytotoxicity in mammalian cells. They also showed the suppressive effect of DNA damage induced by $H_2O$$_2$ or KO$_2$ with dose-dependent manner in single cell gel electrophoresis(SCGE) assay. On the other hand, they have an anticlastogenic effect against adriamycin-induced micronucleated reticulocyte in peripheral blood of mice. These results suggest that the mechanism of inhibition by 70% ethanol extract of Alpinia officinarum and galangin against reactive oxygen species (ROS)-induced genotoxicity or cytotoxicity is due, at least partly, to their antioxidative and free radical scavenging properties without pro-oxidant effect. All these results indicate that 70% ethanol extract of Alpinia officinarum and galangin may be useful for protection against ROS-induced cytotoxicity and DNA damage.

Ginseng saponin metabolite 20(S)-protopanaxadiol relieves pulmonary fibrosis by multiple-targets signaling pathways

  • Guoqing Ren;Weichao Lv;Yue Ding;Lei Wang;ZhengGuo Cui;Renshi Li;Jiangwei Tian;Chaofeng Zhang
    • Journal of Ginseng Research
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    • v.47 no.4
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    • pp.543-551
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    • 2023
  • Background: Panax ginseng Meyer is a representative Chinese herbal medicine with antioxidant and anti-inflammatory activity. 20(S)-Protopanaxadiol (PPD) has been isolated from ginseng and shown to have promising pharmacological activities. However, effects of PDD on pulmonary fibrosis (PF) have not been reported. We hypothesize that PDD may reverse inflammation-induced PF and be a novel therapeutic strategy. Methods: Adult male C57BL/6 mice were used to establish a model of PF induced by bleomycin (BLM). The pulmonary index was measured, and histological and immunohistochemical examinations were made. Cell cultures of mouse alveolar epithelial cells were analyzed with Western blotting, coimmunoprecipitation, immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay and qRT-PCR. Results: The survival rate of PPD-treated mice was higher than that of untreated BLM-challenged mice. Expression of fibrotic hallmarks, including α-SMA, TGF-β1 and collagen I, was reduced by PPD treatment, indicating attenuation of PF. Mice exposed to BLM had higher STING levels in lung tissue, and this was reduced by phosphorylated AMPK after activation by PPD. The role of phosphorylated AMPK in suppressing STING was confirmed in TGF-b1-incubated cells. Both in vivo and in vitro analyses indicated that PPD treatment attenuated BLM-induced PF by modulating the AMPK/STING signaling pathway. Conclusion: PPD ameliorated BLM-induced PF by multi-target regulation. The current study may help develop new therapeutic strategies for preventing PF.

Correlation Between Response to Induction Chemotherapy and Subsequent Radiotherapy in Previously Untreated Patients with Squamous Cell Carcinomas of the Head and Neck (두경부의 악성종양(편평상피암) 환자에서 유도화학요법에 의한 종양의 관해와 방사선치료에 의한 관해의 상호 관계)

  • Park Woo Yoon;Yoo Seong Yul;Koh Kyoung Hwan;Cho Chul Koo;Park Young Hwan;Shim Youn Sang;Oh Kyung Kyoon;Lee Yong Sik
    • Radiation Oncology Journal
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    • v.8 no.2
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    • pp.207-212
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    • 1990
  • To determine the correlation between the response to induction chemotherapy and subsequent radiotherapy we analyzed the clinical records of 60 patients with locally advanced carcinoma of the head and neck retrospectively who had completed a full course ($2\~3$ cycle) of induction chemotherapy and curative radiotherapy in Korea Cancer Center Hospital between 1986 and 1989. Chemotherapy was administeredd with CDDP+Bleomycin (BP) in 20, CDDP+5-FU (FP) in 37, and hybrid of BP and FP in three patients. Radiotherapy was giver conventionally with a dose of 65 to 75 Gy or more over seven to eight weeks according to the size of lesion. Response rates following induction chemotherapy were $80\%$ for the tumors and $879\%$ for the nodes whereas complete reponse rates were $12\%\;and\;13\%$, respectively. Six months after radiotherapy $67\%$ of the tumors and $77\%$ of the nodes achieved a complete response. Among the 48 tumor responders and the 31 nodal responders to chemotherapy,39 ($81\%$) and 28 ($90\%$), respectively, achieved complete response after radiotherapy. Thus, whether or not the tumor and node respond to induction chemotherapy was predictive of the response to subsequent radiotherapy (p<0.0005 in tumor, p<0.0001 in node). By reanalyzing according to disease subsets (i.e. primary site, T-stage, N-stage) this relationship was not observed at T1-T2 disease (p>0.3). Therefore the tumor or node's response to induction chemotherapy is a predictor for subsequent radiotherapy except in T1-T2 tumors, and complete response to radiotherapy can be expected despite the failure of induction chemotherapy in $T_1-T_2$ tumors.

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Sequential Chemotherapy and Radiation Therapy for Advanced Nasopharyngeal Carcinoma (진행된 비인강암의 화학요법 및 방사선 치료)

  • Park, In-Kyu;Kim, Song-Bo;Yun, Sang-Mo;Kim, Jae-Cheol;Park, Jun-Sik
    • Radiation Oncology Journal
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    • v.11 no.2
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    • pp.259-265
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    • 1993
  • Between January 1985 and July 1992, 52 patients with locally advanced nasopharyngeal carcinoma were studied retrospectively for the effectiveness of sequential chemotherapy and radiation therapy. The male to female ratio was 3.3:1 with a median age of 41 years. Forty patients had squamous cell carcinoma and the remaining 12 had undifferentiated carcinoma. Seven patients had stage III disease and the remainder had stage IV disease at time of presentation. All patients were treated two courses of chemotherapy followed by radiation therapy. Chemotherapy consisted of either CVB (cisplatin, vincristine and bleomycin) or CF (cisplatin and 5-FU). Total radiation dose to the primary site ranged from 6000 cGy to 7500 cGy. Neck nodes were given booster treatment to maximum of 7000 cGy, depending on the extent of disease. Local control, overall survival and disease-free survival rates were analyzed. The complete response (CR) rate to chemotherapy was $15\%$ and the partial response (PR) rate was $46\%,$ for overall major response rate of $61\%.$ The CR rate was $87\%$ after radiation therapy. Median follow-up time was 51 months. The overall survival and disease-free survival rates at 36 months were $54\%\;and\;49\%,$ respectively. Median time to relapse was 15 months. The patterns of initial relapse in CR patients was as follows: locoregional failure only, 12 patients; distant metastasis only,11: both,2. Cox's multivariate regression model revealed that nodal status was the single most important independant prognostic factor influencing disease-free survival (p=0.001). Comparision of these results with other published reports with radiation therapy alone showed that a high rate of initial response to chemotherapy did not translate into local control or survival. At present time radiation therapy alone remains the standard treatment for locoregional cancer of the nasopharyngeal cancer. More controlled clinical trials must be completed before acceptance of chemotherapy as a part of treatment of advanced nasopharyngeal carcinoma.

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Neoadjuvant Chemotherapy and Radiotherapy in Locally Advanced Hypopharyngeal Cancer (국소 진행된 하인두암의 선행 항암화학요법 후 방사선치료)

  • Kim Suzy;Wu Hong-Gyun;Heo Dae-Seog;Park Charn I1
    • Radiation Oncology Journal
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    • v.18 no.4
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    • pp.244-250
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    • 2000
  • Purpose : To see the relationship between the response to chemotherapy and the final outcome of neoadiuvant chemotherapy and radiotherapy in patients with mocanry advanced hypopharyngeal cancer. Methods and Materials :A retrospective analysis was done for thirty-two patients with locally advanced hypopharyngeal cancer treated in the Seoul National University Hospital with neoadiuvant chemotherapy and radiotherapy from August 1979 to July 1997. The patients were treated with Co-60 teletherapy unit or 4MV or 6MV photon beam produced by linear accelerator. Daily fractionation was 1.75 to 2 Gy, delivered five times a week. Total dose ranged from 60.8 Gy to 73.8 Gy. Twenty-nine patients received continuous infusion of cisplatin and 5-FU. Other patients were treated with cisplatin combined with bleomycin or vinblastin. Twenty-four (75$\%$) patients received all three prescribed cycles of chemotherapy delivered three weeks apart. Six patients received two cycles, and two patients received only one cycle. Results :The overall 2-year and 5-year survival rates are 65.6$\%$ and 43.0$\%$, respectively. 5-year local control rate is 34$\%$. Organ preservation for more than five years is achieved in 12 patients (38$\%$). After neoadjuvant chemotherapy, 24 patients achieved more than partial remission (PR): the response rate was 75$\%$ (24/32). Five patients had complete remission (CR), 19 patients PR, and 8 patients no response (NR). Among the 19 patients who had PR to chemotherapy, 8 patients achieved CR after radiotherapy. Among the 8 non-responders to chemotherapy, 2 patients achieved CR, and 6 patients achieved PR after radiotherapy. There was no non-responder after radiotherapy. The overall survival rates were 60$\%$ for CR to chemotherapy group, 35.1$\%$ for PR to chemotherapy group, and 50$\%$ for NR to chemotherapy group, respectively (p=0.93). There were significant difference in five-year overall survival rates between the patients with CR and PR after neoadjuvant chemotherapy and radiotherapy (73.3$\%$ vs. 14.7$\%$, p<0.01). The prognostic factor affecting overall survival was the response to overall treatment (CR vs. PR, p<0.01). Conclusion :In this study, there were only five patients who achieved CR after neoadiuvant chemotherapy. Therefore the difference of overall survival rates between CR and PR to chemotherapy group was not statistically significant. Only the response to chemo-radiotherapy was the most important prognostic factor. There needs to be more effort to improve CR rate of neoadjuvant chemotherapy and consideration for future use of concurrent chemoradiotherapy.

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The Results of Radiation Therapy Alone vs Radiation Plus Chemotherapy of Uterine Cervix Cancer (자궁경부암에서 방사선 단독요법 및 항암화학과 방사선 병용요법의 치료성적)

  • Lee, Myung-Za;Choi, Seog-Young;Chun, Ha-Chung
    • Radiation Oncology Journal
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    • v.13 no.2
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    • pp.181-189
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    • 1995
  • Pupose: Radiation therapy(RT) is conventionally standard treatment for locally advanced stage for uterine cervix cancer. Recently to improve treatment results, combined chemotherapy and radiation therapy was tried We retrospectively analysed our experience of 122 patients. Comparision of the results in 45 patients treated with RT alone and 77 patients treated with RT plus chemotherapy was made Materials and Mathods: From January 1985 to December 1991 122 patients with cervix cancer were treated with whole pelvic external RT and ICR(34 1 ICR, 77 2 ICR, 11 high dose rate ICR) in our department. Forty five patients were treated with RT alone, and 77 patients were treated with combined RT plus chemotherapy Mean age was 58 years(range:29-81). Histologic types were 111 squamous cell carcinoma, 5 large cell carcinoma, 3 adenocarcinoma, and 2 adenosquamous cell carcinoma. According to the FIGO stage 6 had stage $IA(4.9\%),$ 11 had $IIA(9.0\%),$ 37 had $IIB(30.3\%),$ 3 had $IIIA(2.5\%),$ 63 had $IIIB(51.6\%).$ and 2 had stage $IV(1.6\%).$ In 77 patients with RT Plus chemotherapy, 36 patients were treated with VBP(vinblastin, bleomycin, cisplatinum) , 39 patients with cisplatinum plus 5-FU and 2 patients with 5-FU. Results: Complete response after external RT (3960cGy-5500cGy) was achieved in 61 patients$(50\%).$ The actuarial 5 year and 9 rear survival rate was $57.8\%\;and\;53.9\%,$ respectively. Five rear actuarial survival rate was $63.1\%$with RT alone(n=45) and $55.9\%$ with RT plus chemotherapy(n=77). The 5 rear survival rate was $35.5\%$ for 1 course of ICR and $67\%$ for 2 courses of ICR. There was statistically significant advantage of survival with RT alone group who were treated with 2 courses of ICR and dose to the A Point)=8000cGy (4/25 died). In RT plus chemotherapy group, dose response was not seen and there was no difference in 5 year survival between 1 course and 2 course of ICR $(50\%\;vs\;56.8\%),$ and dose to point A less than 8000 cGy and more than 8000 $cGy(55.6\%\;vs\;55.7\%).$ There was no significant difference in survival between RT alone and RT plus chemotherapy for patients with tumor size greater than 3cm in size. Five year survival rate for early stage (Stage IB and IIA) with RT alone group and with RT Plus chemotherapy group was $60\%\;and\;77.0\%,$ respectively In advanced stage (stage IIB, IIIA, IIIB, IVA) the 5 year actuarial survival rate were $62.6\%,$ for RT alone group vs $53.6\%$ for RT plus chemotherapy group. Conclusion: Present study demonstrates that there is no survival advantage with adding chemotherapy in advanced stage of uterine cervix cancer. RT alone is considered as treatment of choice for patients with locally advanced cervix cancer. There was increased survival in RT alone group treated with RT dose above 8000 cGy to point A and 2 course of ICR. but 2 course of ICR and RT dose above 8000 cGy to point A did not affect survival advantage in RT plus chemotherapy group.

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Radiation Therapy for Carcinoma of the Oropharynx (구인두암의 방사선치료)

  • Park, In-Kyu;Kim, Jae-Choel
    • Radiation Oncology Journal
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    • v.14 no.2
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    • pp.95-103
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    • 1996
  • Purpose : A retrospective analysis for patients with oropharyngeal carcinoma who were treated with radiation was performed to assess the results of treatment and patterns of failure, and to identify the factors that might influence survival. materials and methods : From March 1985 through June 1993, 53 patients with oropharyngeal carcinoma were treated with either radiation therapy alone or combination of neoadjuvant chemotherapy and radiation therapy at the Department of Radiation Oncology, Kyungpook National University Hospital. Patients' ages ranged from 31 to 73 years with a median age of 54 years. There were 47 men and 6 women, Forty-two Patients ($79.2\%$) had squamous cell carcinoma, 10 patients ($18.9\%$) had undifferentiated carcinoma and 1 patient ($19\%$) had adenoid cystic carcinoma. There were 2 patients with stage I, 12 patients with stage II, 12 Patients with stage III and 27 patients with stage IV. According to the TNM classification, patients were distributed as follows: T1 7, T2 28, T3 10, T4 7, TX 1, and N0 17, Nl 13, N2 21, N3 2. The primary tumor sites were tonsillar region in 36 patients ($67.9\%$), base of the tongue in 12 patients ($22.6\%$), and soft palate in 5 patients ($9.4\%$). Twenty-five patients were treated with radiation therapy alone and twenty-eight Patients were treated with one to three courses of chemotherapy followed by radiation therapy. Chemotherapeutic regimens used were either CF (cisplatin and 5-fluorouracil) or CVB (cisplatin, vincristine and bleomycin). Radiation therapy was delivered 180-200 cGy daily, five times a week using 6 MV X-ray with or without 8-10 MeV electron beams A tumor dose ranged from 4500 cGy to 7740 cGy with a median dose of 7100 cGy. The follow-up time ranged from 4 months to 99 months with a median of 21 months. Results : Thirty-seven patients ($69.8\%$) achieved a CR (complete response) and PR (partial response) in 16 patients ($30.2\%$) after radiation therapy. The overall survival rates were $47\%$ at 2 years and $42\%$ at 3 years, respectively. The median survival time was 23 months. Overall stage (p=0.02) and response to radiation therapy (p=0.004) were significant prognostic factors for overall survival. The 2-year disease-free survival rate was $45.5\%$. T-stage (p=0.03), N-stage (p=0.04) and overall stage (P=0.04) were significant prognostic factors for disease-free survival. Age, sex, histology, primary site of the tumor, radiation dose, combination of chemotherapy were not significantly associated with disease-free survival. Among evaluable 32 Patients with CR to radiation therapy, 12 patients were considered to have failed Among these, 8 patients failed locoregionally and 4 Patients failed distantly. Conclusion : T-stage, N-stage and overall stage were significant prognostic factors for disease-free survival in the treatment of oropharyngeal cancer Since locoregional failure was the predominant pattern of relapse, potential methods to improve locoregional control with radiation therapy should be attempted. More controlled clinical, trials should be completed before acceptance of chemotherapy as a part of treatment of oropharyngeal carcinoma.

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Efficacy and Tolerance of Pegaspargase-Based Chemotherapy in Patients with Nasal-Type Extranodal NK/T-Cell Lymphoma: a Pilot Study

  • Wen, Jing-Yun;Li, Mai;Li, Xing;Chen, Jie;Lin, Qu;Ma, Xiao-Kun;Dong, Min;Wei, Li;Chen, Zhan-Hong;Wu, Xiang-Yuan
    • 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.

Combined Modality Treatment in Head and Neck Cancer (국소 진행된 두경부암의 병합요법 : 치료 방법에 따른 비교)

  • Park In-Kyu;Lee Ho-Jun;Yun Sang-Mo;Kim Jae-Chul
    • Korean Journal of Head & Neck Oncology
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    • v.17 no.1
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    • pp.32-37
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    • 2001
  • Objectives: We performed this study to compare the short term results of induction chemotherapy and radiotherapy versus concurrent chemoradiotherapy in patients with locally advanced head and neck cancer. Materials and Methods: From Oct. 1985 to May 1998, 121 patients with locally advanced head and neck cancer were treated with induction chemotherapy and radiotherapy (induction group) or concurrent chemoradiotherapy (concurrent group), and a retrospective analysis was done. Induction chemotherapy was done for 97 patients, and concurrent chemotherapy for 24 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Primary site showed nasopharynx(72.2%), oropharynx(27.8%) in induction group, and nasopharynx(50%), oropharynx(50%) in concurrent group. Chemotherapy regimen was CF(cisplatin and 5-fluorouracil) for 67 patients and CVB (cisplatin, vincristine, bleomycin) for 30 patients in induction group, and CF for all of 24 patients in concurrent group. Proportion of patients treated with more than 2 cycles of planned chemotherapy was 94.8% in induction group and 87.5% in concurrent group. Conventionally fractionated radiotherapy with daily fraction size of 1.8-2.0Gy and 5 fractions/week was done. Total dose was 61-95Gy (median 73.4Gy) for induction group, and 69.4-75.4Gy (median 69.4Gy) for concurrent group. Follow-up time was 4-161 months (median 38 months) for induction group, 7-35 months (median 21.5 months) for concurrent group, respectively. Results: According to treatment modality, overall 2-year survival rates were 68.0% for induction group, 74.3% for concurrent group (p>0.05). two-year disease-free survival rates were 51 % and 74% (p=0.05). Complete response rates were 67.4% for induction group and 83.3% for concurrent group (p=0.09). The incidence of grade 3-4 hematologic toxicity (2.1% vs. 25%, p=0.001) and grade 3-4 mucositis (9.3% vs. 37.5%, p=0.002) during radiotherapy was higher in concurrent group. Conclusion: Concurrent chemoradiotherapy showed a trend of improvement in short-term survival and treatment response when compared with induction chemotherapy and radiotherapy in locally advanced head and neck cancer. A more controlled randomized trial is needed.

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Three cases of primary mediastinal Nonseminomatous germ cell tumors (원발성 종격동 비정상피종성 생식세포종 3예)

  • Lee, Soon Il;Yong, Suk Joong;Song, Kwang Seon;Shin, Kye Chul;Yang, Kyung Moo;Cho, Mee Yon;Lim, Hyung Rae;Yoo, Kwang Ha;Cho, Hwa Sang;Yoo, Jong Kil;Song, Jong Oh
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.6
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    • pp.1008-1018
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    • 1996
  • Primary mediastinal nonseminomatous germ cell tumor is extremely rare. Apart from rarity and large size, mediastinal germ cell tumors show striking similarity to testicular tumors in age, incidence, and tumor type. The symptoms associated with these tumors are related mainly to size, invasion of neighboring structures, and distant metastases. Tissue diagnosis is obtained by biopsy of the primary lesion or by biopsy of metastatic sites. Tumors often present with advanced bulky disease, which are unresectable. So these tumors require an aggressive multidisciplinary approach to management. Optimal management includes aggressive surgical debulking and early use of cisplatin-bleomycin-based combination chemotherapy. Serial biomarker measurements permit early recognition of recwrence and improved timing of surgical intervention. The prognosis for mediastinal germ cell tumors is poor, not only because they are far advanced at the time of diagnosis but also because some of the tumors-such as embryonal carcinomas, choriocarcinomas, and endodermal sinus tumors-are very aggressive. In these cases, we present three young male patients with large mass on anterior mediastinum. Tissue diagnosis was obtained by primary lesion biopsy. All patients received surgical debulking and combination chemotherapy and experienced a brief response and eventually had relapses. We report these cases with a review of literatures.

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