• Title/Summary/Keyword: etoposide-cisplatin

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Inductions of Caspase-, MAPK- and ROS-dependent Apoptosis and Chemotherapeutic Effects Caused by an Ethanol Extract of Scutellaria barbata D. Don in Human Gastric Adenocarcinoma Cells

  • Shim, Ji Hwan;Gim, Huijin;Lee, Soojin;Kim, Byung Joo
    • Journal of Pharmacopuncture
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    • v.19 no.2
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    • pp.129-136
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    • 2016
  • Objectives: The crude extracts of Scutellaria barbata D. Don (SB) have traditionally demonstrated inhibitory effects on numerous human cancers both in vitro and in vivo. Gastric cancer is one of the most common types of cancer on world. The authors investigated the effects of an ethanol extract of Scutellaria barbata D. Don (ESB) on the growth and survival of MKN-45 cells (a human gastric adenocarcinoma cell line). Methods: The MKN-45 cells were treated with different concentrations of ESB, and cell death was examined using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Analyses of sub-G1 peaks, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to determine the anti-cancer effects of SB on MKN-45 cells. Also, intracellular reactive oxygen species (ROS) generation was investigated. Results: ESB inhibited the growth of MKN-45 cells, caused cell cycle arrest, and increased the sub-G1 population. In addition, ESB markedly increased mitochondrial membrane depolarization and the activities of caspase-3 and -9. ESB exerted anti-proliferative effects on MKN-45 cells by modulating the mitogen-activated protein kinase (MAPK) signaling pathway and by increasing the generation of ROS. Furthermore, combinations of anti-cancer drugs plus ESB suppressed cell growth more than treatments with an agent or ESB, and this was especially true for cisplatin, etoposide, and doxorubicin. Conclusion: ESB has a dose-dependent cytotoxic effect on MKN-45 cells and this is closely associated with the induction of apoptosis. ESB-induced apoptosis is mediated by mitochondria-, caspase- and MAPK dependent pathways. In addition, ESB enhances ROS generation and increases the chemosensitivity of MKN-45 cells. These results suggest that treatment with ESB can inhibit the proliferation and promote the apoptosis of human gastric adenocarcinoma cells by modulating the caspase-, MAPK- and ROS-dependent pathway.

A Case of Unknown-Primary Small Cell Carcinoma of the Neck (경부에 발생한 원발불명의 소세포암 1례)

  • Lee So-Young;Kim Young-Chul;Hong Chang-Kyoun;Kim Jung-A;Kim Sung-Whan;You Jin-Young;Noh He-Il;Kim Hoon-Kyo
    • Korean Journal of Head & Neck Oncology
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    • v.16 no.2
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    • pp.216-219
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    • 2000
  • Small cell carcinoma usually occurs in lung, but extrapulmonary small cell carcinomas can occur in any sites of body. Most sites of extrapulmonary small cell carcinoma reported were esophagus. And small cell carcinomas occurred in head and neck area were reported rarely. Extrapulmonary small cell carcinoma could be diagnosed when there is no evidence of primary lung lesion on chest X-ray, CT scan of chest and bronchoscopy. The authors experienced a case of small cell carcinoma of left submandibular lymph node in 64-year-old male patient. Biopsy specimen showed poorly differentiated carcinoma but immunohistochemical study showed small cell carcinoma. The chest X-ray and CT scan of chest showed no evidence of primary lung lesion. The patient received chemotherapy(etoposide plus cisplatin) and concurrent chemoradiotherapy using weekly taxol which resulted in good clinical remission. He is still alive 8 months after diagnosis without evidence of lung disease. We report our case with a brief review of literatures.

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Outcomes of Malignant Ovarian Germ-Cell Tumors Treated in Chiang Mai University Hospital over a Nine Year Period

  • Neeyalavira, Vithida;Suprasert, Prapaporn
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4909-4913
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    • 2014
  • Malignant ovarian germ cell tumors (MOGCT) are rare neoplasms that most frequently occur in women at a young reproductive age. There have been limited data regarding this disease from Southeast Asian countries. We therefore conducted a retrospective study to analyze the clinical characteristics and the treatment outcomes of MOGCT treated at our institute between January, 2003 and December, 2012. Seventy-six patients were recruited from this period with the mean age of 21.6 years and 11.8% were pre-puberty. The two most common symptoms were pelvic mass and pelvic pain. Two-thirds of the studied patients presented at an early stage. The most common histology was immature teratoma (34.2%) followed by endodermal sinus tumor (28.9%), dysgerminoma (25%), mixed type (10.5%) and choriocarcinoma (1.3%). Over 80% of these patients received fertility sparing surgery and about 70% received adjuvant chemotherapy with the complete response rate at 73.3% and partial response at 11.1%. The most frequent chemotherapy was BEP regimen (bleomycin, etoposide, cisplatin). With the mean follow up time at 56.0 months, 12 patients (15.8%) developed recurrence and only an advanced stage was the independent prognostic factor. The ten year progression free survival (PFS) and overall survival rate of our study were 81.9% and 86.2%, respectively. In conclusion, MOGCT often occurs at a young age. Treatment with fertility sparing operations and adjuvant chemotherapy with a BEP regimen showed a good outcome. An advanced stage is a significant prognostic factor for recurrence.

Ovarian Cancer in Children and Adolescents: Treatment and Reproductive Outcomes

  • Chaopotong, Pattama;Therasakvichya, Suwanit;Leelapatanadit, Chairat;Jaishuen, Atthapon;Kuljarusnont, Sompop
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4787-4790
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    • 2015
  • Objective: To review ovarian cancer cases in children and adolescents in Siriraj Hospital and assess the prognosis, recurrence of disease, and reproductive outcomes after treatment. Materials and Methods: A retrospective descriptive study was conducted in ovarian cancer patients 21 years and younger who had been treated at Siriraj Hospital between January 1990 and December 2009. Medical records were reviewed and relevant data were recorded. Results: A total of 48 cases met the criteria; their mean age was 16.4 years. Abdominal distension was the major symptom. 91.6% were germ cell tumors and the remaining cases were sex cord-stromal and epithelial tumors. More than half (25/48 cases) presented with stage I disease. The most common used chemotherapy regimen for germ cell tumors was BEP (bloemycin, etoposide, cisplatin). Most of patients had favorable outcomes; 46/48 cases had complete remission and retained their good health at the time of the review. We had only one recurrent case and one dead case. Ten of contacted patients had married and 3 of them had successful full-term pregnancies. Conclusions: Ovarian malignancy in children and adolescents is a rare disease. The authors reported 48 cases in 20 year-period of work. Most of them have favorable outcomes. Return of ovarian function and fertility are the topics of interest.

Is Diabetes Mellitus a Prognostic Factor for Survival in Patients with Small Cell Lung Cancer?

  • Inal, Ali;Kaplan, M. Ali;Kucukoner, Mehmet;Urakci, Zuhat;Karakus, Abdullah;Nas, Necip;Guven, Mehmet;Isikdogan, Abdurrahman
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1491-1494
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    • 2012
  • Background: Previous studies have pointed to many different prognostic factors for small cell lung cancer (SCLC) but diabetes mellitus (DM) has not been clearly or consistently identified as of prognostic value. The aim of this study was to investigate the prognostic significance of the characteristics of patients and clinical laboratory tests in SCLC. Specifically, we investigated that the impact of DM for survival in the patients receiving first-line etoposide plus cisplatin (EP) chemotherapy. Methods: We retrospectively reviewed 161 patients with SCLC with a focus on DM and other potential prognostic variables were chosen for univariate and multivariate analyses with respect to survival. Result: Among the sixteen variables of univariate analysis, five were identified to have prognostic significance: performance status (PS) (p<0.001), stage (p=0.001), DM (p=0.005), serum albumin (p<0.001) and hemoglobin levels (p=0.03). Multivariate analysis showed PS, stage and serum albumin level to be independent prognostic factors for survival (p=0.02, p=0.02 and p=0.009 respectively), but DM was not an independnet factor. Conclusion: In conclusion, PS, stage and serum albumin level were identified as important prognostic factors, while DM at the time of diagnosis of SCLC did not have prognostic importance for survival.

Outcome of the Teratoma in Pediatric Surgical Patients (소아외과 환자에서 기형종의 치료 결과)

  • Lee, Ho-Kyun;Park, Kyung-Sub;Choi, Soo-Jin-Na;Kim, Shin-Kon;Chung, Sang-Young
    • Advances in pediatric surgery
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    • v.9 no.2
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    • pp.94-97
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    • 2003
  • The teratoma is a unique complex neoplasm and is one of the most frequent pediatric tumors originated from the extragonadal germ cells. Mature teratoma is composed of mature differentiated tissues, while immature teratoma always contains embryonic tissues of variable degrees of immaturity, especially in the neuroepithelial elements. Diagnosis of teratoma is relatively easy by conventional radiologic study, but the immaturity can be identified only by histopathological examination. Between January 1993 to December 2002, 63 cases of teratoma were operated and analysed retrospectively at the Chonnam University Hospital Female to male ratio was about 3:1 and age distribution was relatively even. Among 63 cases, gonadal teratoma was the most common (52.4%), followed by sacrococcygeal (25.4%), retroperitoneal (9.5%) and mediastinal teratoma (9.5%). Fifty-six cases were mature teratomas and seven were immature teratomas. Alpha-fetoprotein (AFP) was elevated in 4 of 6 immature cases, but in 2 of 51 mature ones Elevated AFP progressively returned to normal range by 1 month after operation in all. Complete excision of the mass was performed, and major complication was not noticed. In five immature cases, PEB chemotherapy (Cisplatin, Etoposide, Bleomycin) was performed. Two of 2 cases in histological grade II were well tolerated to the aggressive chemotherapy. One of three cases in grade III expired due to severe bone marrow depression, and two of them expired by tumor recurrences. In conclusion, immature teratoma in histological grade III showed high potentiality of recurrence. Therefore, postoperative chemotherapy has to be applied to the high graded immature tumors.

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Extracellular acidity enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis via DR5 in gastric cancer cells

  • Hong, Ran;Han, Song Iy
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.513-523
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    • 2018
  • The tumor microenvironment greatly influences cancer cell characteristics, and acidic extracellular pH has been implicated as an essential factor in tumor malignancy and the induction of drug resistance. Here, we examined the characteristics of gastric carcinoma (GC) cells under conditions of extracellular acidity and attempted to identify a means of enhancing treatment efficacy. Acidic conditions caused several changes in GC cells adversely affecting chemotherapeutic treatment. Extracellular acidity did inhibit GC cell growth by inducing cell cycle arrest, but did not induce cell death at pH values down to 6.2, which was consistent with down-regulated cyclin D1 and up-regulated p21 mRNA expression. Additionally, an acidic environment altered the expression of atg5, HSPA1B, collagen XIII, collagen XXAI, slug, snail, and zeb1 genes which are related to regulation of cell resistance to cytotoxicity and malignancy, and as expected, resulted in increased resistance of cells to multiple chemotherapeutic drugs including etoposide, doxorubicin, daunorubicin, cisplatin, oxaliplatin and 5-FU. Interestingly, however, acidic environment dramatically sensitized GC cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Consistently, the acidity at pH 6.5 increased mRNA levels of DR4 and DR5 genes, and also elevated protein expression of both death receptors as detected by immunoblotting. Gene silencing analysis showed that of these two receptors, the major role in this effect was played by DR5. Therefore, these results suggest that extracellular acidity can sensitize TRAIL-mediated apoptosis at least partially via DR5 in GCs while it confers resistance to various type of chemotherapeutic drugs.

Prognostic factores in the treatment of lung cancer related to postoperative radiochemoimmunotherapy; BPM therapy[PS-K] of lung cancer followed by surgery (폐암절제례의 예후와 면역요법)

  • 김광택
    • Journal of Chest Surgery
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    • v.26 no.1
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    • pp.47-53
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    • 1993
  • The high relapse rate after curative surgery of lung cancer suggests that tumor cells are remained at the site of resection and in the distant organs. Postoperative radiochemoimmunotherapy including protein-bound polysaccharide PS-K[Copolang] and/or chemotherapy to improve the prognosis in lung cancer has been adopted. The patients with lung cancer who were treated with a combined modality therapy after surgery were reviewed to determine the effects of adjuvant immunotherapy[PS-K] and the relationship between midterm survival and clinicopathologic variables. During the past 5 years, 95 patients with lung cancer underwent resective operation. Of them, 30 cases were curative surgery, 29 were relative curative surgery, and the remainders were non-curative surgery. Postoperative combination therapies consisted of three types of therapies: postoperative BRM[biological response modifiers] with PS-K [Copolang] 50 mg/kg for 24 weeks[Group 1], chemoimmunotherapy with chemotherapy[a combination of cisplatin, etoposide, vindesine] and PS-K [Group 2], radioimmunotherapy with postoperative prophylactic irradiation to the mediastinum at total dose of 54 Gy-60 Gy and PS-K [Group 3] and surgery without adjuvant therapy[Group 4]. Twenty months survival rates of localized disease [Stages I and II] treated with PS-K, with radioimmunotherapy and no therapy were 73 %, 60 %, and 50 %, respectively [p [0.05]. Three-year survival rates of regionally advanced cases [stage Ilia and IIIb] were 23 % in Group 1.57 % in Group 2.20 % in Group 3, and 0 % in Group 4, respectively.According to above results, we suggest that postoperative combination therapy including PS-K might improve the prognosis of lung cancer. The similar survival pattern of patients with squamous cell carcinoma and adenocarcinoma treated with BRM, chemoimmunotherapy or radioimmunotherapy need to evaluate the role of postoperative immunotherapy[PS-K] in randomized studies.

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Augmentation of the Cytotoxic Effects of Anticancer Drugs by $(\pm)$-ar-Turmerone and Extracts of the Lithosperma and Scutellaria Roots against Human Leukemia Cell Lines (백혈병 세포주에 대한 $(\pm)$-ar-Turmerone, 자근 및 황금추출물에 의한 항암제의 세포독성 증강효과)

  • 이윤영;유관희;김삼용;안병준
    • YAKHAK HOEJI
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    • v.35 no.3
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    • pp.203-215
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    • 1991
  • Using the calorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT)assay, we evaluated the chemosensitivity of 8 anticancer drugs{vincristine(VCR), vinblastine(VBL), adriamycin(ADR), cisplatin(CPDD), etoposide(VP-16), cytosine arabinoside(ara-C), bleomycin (Bleo) and cyclophosphamide(CYC)} and the cytotoxicity-enhancing effects of ($\pm$)-ar-turmerone and the extracts of the crude drugs {Lithospermum eythrorhizon(LE) and Scutellaria baicalensis (SB)} on the above mentioned anticancer drugs against HL-60 and KG-1 cells among 8 anticancer drugs, VCR, VBL, ADR, and CPDD inhibited the growth of both cell lines by more than 50%, while VP-16, ara-C, Bleo, and CYC were less effective. ($\pm$)-ar-Turmerone had significant inhibitory effects against both cell lines, showing the ID$_{50}$ values of 11.730 $\mu\textrm{g}$/ml and 0.292 $\mu\textrm{g}$/ml for HL-60 and KG-1 cells. respectively. But the extracts of LE and SB roots showed no significant cytotoxic effects. According to ID$_{50}$ values, the cytotoxicities of VCR, VBL and ADR against HL-60 were enhanced two, eight and three times by mixing ($\pm$)-ar-turmerone, five, seven and three times by adding the extract of LE root, and twenty, six and three times by mixing the extract of SB root, respectively. The cytotoxicities of the above mentioned drugs against KG-1 cell were enhanced two, seven and three times by mixing ($\pm$)-ar-turmerone, two, three and three times by combining wilth the extract of LB root, and two, five and two times by adding the extract of SB root, respectively. The cytotoxicity-potentiating effects of ($\pm$)-ar-turmerone and the extracts of LE and SB roots against HL-60 cell were greater than KG-1 cell.

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Effects of enucleation and chemotherapy in advanced intraocular and intraorbital retinoblastoma with or without radiotherapy (진행된 안구내 및 안와내 망막모세포종에서 안구적출술과 항암화학치료 및 방사선조사 유무에 따른 효과)

  • Lee, Jae Min;Lee, Hyun Dong;Hah, Jeong Ok
    • Clinical and Experimental Pediatrics
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    • v.51 no.1
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    • pp.84-88
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    • 2008
  • Purpose : Radiotherapy is effective in local treatment for retinoblastoma. However, asymmetric facial hypoplasia after radiation is a serious late effect. This study was performed to investigate the effects of enucleation and chemotherapy with or without radiotherapy in advanced intraocular and intraorbital retinoblastoma. Methods : Between 1985 October and 2006 December, the records of thirty five patients who were diagnosed as retinoblastoma at Yeungnam University Hospital were reviewed. Advanced intraocular and intraorbital retinoblastoma patients classified as Reese-Ellsworth group III, IV, and V and Grabowski- Abramson class II were selected for the study. Results : Eighteen patients were enrolled in this study. All patients were enucleated and had received chemotherapy. Nine patients received radiotherapy and nine patients didn't receive radiotherapy. Tumor cells were found on resection margin of optic nerve in five of nine patients who received radiotherapy, but none of nine who didn't receive radiotherapy. Chemotherapy included vincristine, adriamycin, cyclophosphamide, VM-26, cisplatin before 2001, and vincristine, etoposide, and carboplatin after 2001. There were no recurrences or metastases in nine patients who didn't receive radiotherapy. But two of nine patients who received radiotherapy had metastases to brain. However, all survivors who received radiotherapy had significant facial asymmetry. Conclusion : In advanced intraocular and intraorbital retinoblastoma without tumor cell on resection margin of optic nerve, enucleation and chemotherapy without local radiotherapy appears to be safe for long-term survival. However, in those with tumor cells on resection margin of optic nerve, enucleation and chemotherapy with local radiotherapy seems to be necessary to improve survival.